dcsimg
Link to U.S. Department of Health and Human Services - www.hhs.gov
Skip Navigation
Physical Activity Guidelines for Americans Banner


Get Active healthfinder.gov - Your Source for Reliable Health Information

Physical Activity Guidelines Advisory Committee Report
Part G. Section 7: Cancer

List of Figures

Introduction

In the United States, an estimated 45% of men and 38% of women will develop cancer in their lifetimes (1). Only 10% to 15% of cancers are due to an inherited genetic predisposition, and the remainder is thought to be due to lifestyle or environmental factors (2). The International Agency for Research on Cancer (IARC) estimates that 25% of cancer cases worldwide are due to overweight and obesity and a sedentary lifestyle (2). The most consistent associations between increased physical activity and reduced cancer risk have been observed for colon and breast cancers. Growing evidence supports a reduced risk of endometrial and lung cancers in physically active versus sedentary persons. A large number of studies have investigated the association between physical activity and prostate cancer and, in summary, have found no association between physical activity and risk of prostate cancer. Few data are available to determine whether physical activity affects risk of cancer at other sites.

A total of 1,437,180 new cancer cases and 565,650 deaths from cancers were projected to occur in the United States in 2008, and cancer is the leading cause of death for men and women younger than age 80 (1). A growing body of literature supports a role for physical activity in improving cancer prognosis and quality of life (3). Therefore, it is imperative to identify lifestyle factors that could be modified to reduce the impact of cancer.

Review of the Science

Overview of Questions Asked

This chapter addresses 3 specific questions:

  1. What are the associations between physical activity and incidence of specific cancers? If an association exists, what is the dose-response pattern?
  2. What are the effects of physical activity on cancer survivors, including late and long-term effects of treatment, quality of life, and prognosis?
  3. What mechanisms explain the associations between physical activity and cancers?

Data Sources and Process Used to Answer Questions

This chapter reviews the available epidemiologic data on associations between physical activity and risks of specific cancers, the intervention study data on physical activity in cancer survivors, and the human experimental data on mechanisms that might explain the links between physical activity and cancer. The Cancer subcommittee began its literature review with the Physical Activity Guidelines for Americans Scientific Database, which includes publications since 1995 (see Part F: Scientific Literature Search Methodology, for a full description of the Database). This search was augmented with MEDLINE searches of English-language articles using the terms "physical activity," "exercise," and "cancer." In addition, the subcommittee used several comprehensive literature reviews (2;4-8).

Because all of the studies that examined the association of physical activity with risk of cancer are observational epidemiologic studies, causality cannot be inferred. However, chance is unlikely as an alternate explanation because many of the results were statistically significant, particularly for colon and breast cancer.

Question 1. What Are the Associations Between Physical Activity and Incidence of Specific Cancers? If an Association Exists, What Is the Dose-Response Pattern?

Conclusions

A large body of epidemiologic data exists on the association between physical activity and the risk of developing various types of cancer. Although the direct evidence of these associations derives only from observational studies, randomized controlled trials (RCTs) have provided indirect evidence by examining the association of physical activity with markers of cancer risk, such as circulating levels of sex hormones, insulin, and cytokines.

The observational data are clearest for colon and breast cancer, with case-control and cohort studies supporting a moderate, inverse relation between physical activity and the development of these cancers. Individuals engaging in aerobic physical activity for approximately 3 to 4 hours per week at moderate or greater levels of intensity have on average a 30% reduction in colon cancer risk and a 20% to 40% lower risk of breast cancer, compared with those who are sedentary. A dose-response relation also is apparent, with risk decreasing at higher levels of physical activity. However, little information is available regarding what additional amounts and intensity of physical activity are associated with additional risk reductions; it also is unclear what the magnitude of the additional decrements in risk may be. The available evidence suggests that at least 30 to 60 minutes per day of moderate to vigorous intensity physical activity is required to significantly lower the risk of colon and breast cancer.

Compared with sedentary people, the available epidemiologic data suggest that active people have approximate reductions in risk of lung, endometrial, and ovarian cancers of 20%, 30%, and 20%, respectively. The data overall do not support associations of physical activity with prostate or rectal cancers. Too few data exist regarding the other site-specific cancers to make reasonable conclusions.

Rationale

Breast Cancer

Overall Associations

More than two dozen prospective cohort studies (9-34), and an even greater number of population-based case-control studies (35-71) have examined the relation between physical activity and breast cancer risk. These studies have primarily assessed the role of recreational physical activity on breast cancer risk. Overall, most studies suggest that physically active women have a lower risk of developing breast cancer than sedentary women. The majority of reported cohort studies (10-15;17;18;20-22;24;27;29;31-34) have reported a reduction in risk with physical activity ranging from 20% to 80%, and a number of population-based case-control studies (35-37;41-49;51;53;54;56;69-71) have reported reduction in risk ranging from 20% to 70%. In a meta-analysis of 23 studies focused on physical activity in adolescence and young adulthood, a summary relative risk (RR) estimate of breast cancer for highest versus lowest category of physical activity was 0.81 (95% CI 0.73-0.89), and each 1-hour increase of recreational physical activity per week was associated with a 3% (95% CI 0%-6%) risk reduction (72). A more extensive systematic review of recreational activity and breast cancer risk included 19 cohort and 29 case-control studies (73). The review concluded that evidence was strong that physical activity reduced risk of postmenopausal breast cancer by 20% to 80%, and that each additional hour of physical activity per week reduced risk for breast cancer by 6% (95% CI 3%-8%). They further concluded that the effect of physical activity on premenopausal breast cancer risk was a more modest 15% to 20% reduction.

The relevant lifetime periods for the effects of physical activity on breast cancer risk are not established. Lifetime recreational physical activity (35;51;54;64), adolescent physical activity (15;17;24;35;42;45;47), and physical activity at various life points (10-14;17;18;22;24;37;47;49;51;60) have been associated with lower breast cancer risk in several studies. Studies examining risk more broadly for specific decades of life also have observed an inverse association with some or all examined time periods (24;45;58;59). Furthermore, physical activity after menopause has been found to reduce breast cancer risk (12;22;24). Other studies that specifically looked at physical activity at various life periods have not found a reduced breast cancer risk with physical activity at any time (25).

Associations for Specific Subgroups

Within the United States, associations between increased physical activity and decreased breast cancer risk have been observed in multiethnic populations (24;70;71). These observations also hold true for specific racial and ethnic populations, including black (46;70), Hispanic (49;71), and Asian American women (56).

Results from some studies with sufficient numbers in subgroup populations suggest that the association with physical activity may be stronger in women without a family history of breast cancer than in those with a family history (22;34;51;69), although other large studies have found that women with as well as women without a family history of breast cancer had reduced risk of breast cancer with increasing physical activity (24;32). Several previous studies reported a greater reduction in risk with increasing physical activity among parous compared to nulliparous women (34;35). However, other studies have either observed the opposite finding with risk reduction greater in nulliparous women (32;44), or have found no effect modification of parity (24). One study found that physical activity may be more strongly associated with reduced risk of postmenopausal breast cancer in women who do not use menopausal hormones (22;71), though other studies found that physical activity effect did not change according to menopausal hormone use (16;24;32;40;64).

In 4 studies, researchers examined effect modification by adult weight gain (14;17;45;74), and 1 study reported a greater reduction in risk among women who had less than a 17% increase in adult weight (74). Several studies documented a greater reduction in risk among leaner women compared to heavier women (11;24;44;51), although other studies found that physical activity reduced risk of breast cancer in women with all levels of body mass index (BMI) (32;34).

Two cohort studies have addressed the effect of physical activity on breast cancer within the context of other variables related to energy balance, specifically adiposity and dietary energy intake. One study found evidence that premenopausal women who did not participate in vigorous activity, were overweight or obese (BMI greater than 25 kg/m2), and had a relatively high calorie intake (more than 1,970 kilocalories per day, as determined from a food frequency questionnaire), had a statistically significant 60% increased risk of breast cancer compared with active, normal weight women with lower calorie intake (26). Another cohort study found that women with the highest quartile of energy intake, were obese, and participated in less than 4 hours per week of vigorous physical activity, had a RR of 2.1 (95% CI 1.27-3.45) compared with normal or overweight, active women who had the lowest quartile of calorie intake (31).

In hypothesizing about the reasons for the effects of energy balance on breast cancer risk, investigators speculate that, in addition to the potential role of obesity as an effect modifier, obesity possibly may be on the causal pathway between physical activity and postmenopausal breast cancer development. Specifically, physical activity reduces levels of adiposity, and subsequently reduces adipose tissue production of estrogen and testosterone, both of which can promote breast carcinogenesis or progression. However, most studies of physical activity and breast cancer have adjusted for BMI as a proxy for adiposity, and an inverse association between physical activity and breast cancer risk persisted. Thus, it is likely that physical activity may have some effect on breast cancer risk independent of their mutual relation with adiposity.

Dose-Response Pattern

Several studies have tried to quantify the level of physical activity required for a decreased risk of breast cancer. Investigators have reported statistically significantly lower rates of breast cancer among women exercising at least 1 hour per week (14); exercising at least 3.8 hours per week (primarily vigorous exercise) (35); exercising to keep fit at least 4 hours per week (11); and exercising vigorously at least 7 hours per week (46). Other investigators have observed significantly lower rates among women expending at least 1,500 kilocalories per week (18) (approximately 4 hours per week of moderate-intensity activity); at least 15.3 metabolic equivalent (MET)-hours per week (approximately 4 hours per week of moderate-intensity activity) (41); and at least 17.6 MET-hours per week (4 to 5 hours per week of moderate-intensity activity) (74). Two reports from the same study found significantly lower rates of breast cancer only among women who exercised vigorously on a daily basis during the ages to 14 to 22 years (45;68). Finally, in a study where total physical activity over the lifetime was assessed, significantly lower breast cancer rates were seen in women who expended at least 47.5 MET-hours per week per year in total activity (48). The impact of these various levels of activity on reducing risk has varied from 20% to 40%. However, other studies that specifically looked at dose-response have had not found an effect of any dose of exercise on breast cancer risk (28;30). Overall, it appears that at least 4 to 7 hours per week of moderate to vigorous intensity physical activity is required to produce a statistically significant reduction in risk, although some evidence suggests greater reduction in risk with greater amount of activity, such that 1 hour per day of moderate or vigorous activity produces greater reduction in risk compared with the Surgeon General recommendation of 30 minutes per day on most days of the week (4).

Tumor Characteristics

The incidence of in situ breast cancer is largely influenced by prevalence of screening, and therefore it is important to examine the effects of physical activity on invasive breast cancer separately from that on in situ breast cancer. Furthermore, breast cancers consist of distinct biological subtypes that are strongly related to prognosis and that may differ in etiology including tumor responsiveness to hormones (i.e., estrogen and progesterone receptor [ER/PR] status positive or negative), and other tumor characteristics (e.g., Her2neu receptor status, and other proliferative indices). A few studies have separately examined the association between physical activity and in situ versus invasive breast cancer, however, very few have examined physical activity effects separately in hormone receptor positive or negative tumors, and none has considered other tumor characteristics. In one study, researchers examined the association between physical activity and breast cancer stratified by stage of disease and found risk reduction to be greater for localized invasive disease compared to either in situ or regional/distant breast cancer (54). A recent large cohort study found a greater risk reduction for in situ (RR 0.69, P for trend 0.04) than for invasive breast cancer (RR 0.80, P for trend 0.02) (34). One case-control study focused specifically on in situ breast cancer, and found that risk of this stage of breast cancer was approximately 35% lower in women reporting any lifetime exercise activity compared with sedentary women (54). Two studies also reported risk ratios separately for ER/PR positive and negative tumors, but neither found a difference in risk by ER/PR subtype (18;75). A recent cohort study found that women who reported high versus low levels of physical activity at enrollment had a 13%, 33%, and 20% decreased risk of developing ER+/PR+, ER+/PR−, and ER−/PR− breast cancer, respectively (29). Another large cohort study found the greatest risk reduction from increased physical activity for ER−/PR− breast cancer (34). Most other studies have included too few women with hormone receptor negative disease to be able to assess the association of physical activity with risk of this subtype of breast cancer.

Type of Physical Activity

An association of sedentary occupations with increased risk of breast cancer has been documented in reports from some (11;17;27) but not other (76) prospective cohort studies. Published reports from some (43;47;48;53;61;77) but not other (41;44;52;55;56) population-based case-control studies also document an inverse association between occupational physical activity and breast cancer risk.

The effect of low-intensity activity (such as household activities, gardening, dancing, leisurely walking, or other activities with a MET score below 4) on breast cancer risk is still unclear, but may be of importance, particularly for postmenopausal breast cancer, as a large portion of activity among postmenopausal and elderly women is not vigorous. Although previous studies have examined the association between leisure-time physical activity, such as walking, biking, swimming, and aerobics, few studies have included the effects of other low-intensity activities, such as gardening, housework, or shopping, in their calculation of leisure-time physical activity. This may lead to an underestimation of true energy expenditure, especially among groups of women who do not have access to recreational or sports activity. In support of the importance of household activity, a recent large European cohort study found that for women in the highest versus lowest household activity quartile, risks for postmenopausal and premenopausal breast cancer were reduced by 19% (P for trend 0.0001) and 29% (P for trend 0.0003), respectively (33).

Prostate Cancer

Overall Associations

A number of epidemiologic studies have examined physical activity and prostate cancer risk (28;78-123), including 25 cohort studies (28;78;80-82;87-89;91-102;117;119-121;123) and 14 case-control studies (104-116;118). Several of the cohort studies (78;80;81;94;117) included prostate cancer mortality or advanced or metastatic prostate cancer as at least one endpoint. One study (91) also examined the association between cardiopulmonary fitness and risk of prostate cancer.

Of these studies, 19 found some suggestion for an inverse relation between physical activity and prostate cancer (80;81;87;89;91;93;94;96;97;101;102;104;105;109;112;113; 117;120;123). No overall association between physical activity and prostate cancer was found in 14 studies (28;82;88;95;98-100;106;108;110;114;115;119;121), and an increased risk of prostate cancer among physically active men was found in some studies (78;92;107;111). The size of the association ranged from an 80% reduction in prostate cancer risk for the highest physical activity levels (113) to a 220% increased risk in one study (111).

Associations for Specific Subgroups

No consistent subgroup effects have been defined for demographic or health factors such as age, race/ethnicity, or BMI. A recent study found that, among men with a family history of prostate cancer, risk for those in the highest quartile of physical activity was reduced by 52%, compared to that for those in the lowest quartile of physical activity. Those without a family history had no risk reduction (115).

Dose-Response Pattern

Several studies have attempted to quantitate a dose-response association of prostate cancer risk with levels of physical activity (82;87;88;91-96;98;100-102;104-106;108-110;112-118;120;121). A statistically significant trend toward decreasing prostate cancer risk with increasing physical activity level was observed in several studies (87;93;94;102;104;105;113;118;120), although this was limited to advanced disease in two studies (120;124). In one study, a 74% reduction in prostate cancer risk was found in the highest compared to the lowest quartile of fitness level (91).

Type of Physical Activity

Occupational activity was associated with a decreased risk of prostate cancer in several studies (80;81;93;97;105;113;116) and recreational activity decreased risk of either overall or advanced prostate cancer in several additional studies (91;93;94;96;101;104;115;117). In one study, non-significant risk decreases were found for occupational and recreational activity but an increased risk was observed for household activity (115). No study differentiated between types of recreational activity, such as aerobic or resistance exercise, or to their subtypes such as jogging versus walking. Rather, activities were combined into measures of MET-hours per week, or to measures of frequency or total duration of activity per week.

Effect of Tumor Detection

One consideration for prostate cancer is the effect of screening. Prostate-specific antigen (PSA) screening for early detection became widespread in the United States in the 1990s. If physically active men also are more health conscious (i.e., they are more likely to be screened for prostate cancer), it may result in higher observed rates of prostate cancer among these men because of increased detection. This notion is supported by several cohort studies (94;117;120), which identified a reduction in risk of aggressive, metastatic, or fatal prostate cancer with increased physical activity level. In contrast, an investigation of physical activity and prostate cancer, diagnosed in 1988 or earlier (before widespread PSA screening was available), among Harvard University alumni found an almost halving of prostate cancer incidence rates among men aged 70 years or older who expended at least 4,000 kilocalories per week in physical activity, compared with those expending less than 1,000 kilocalories per week (84). However, an updated analysis of these men, examining prostate cancer diagnosed after 1988, did not support the earlier observations (100). These inconsistent findings may have been due to bias arising from increased screening for prostate cancer among the most active men.

Colon Cancer

To examine the association between physical activity and colon cancer, the Cancer subcommittee searched the Physical Activity Guidelines for Americans Scientific Database. Because the association of physical activity with colon and rectal cancer appears different (see rectal cancer below), we did not include studies where colorectal cancer was the outcome of interest, as the relation between physical activity and colon cancer likely would be diluted. The search yielded 23 publications eligible for inclusion in the present report.

Overall Association

The 23 publications reviewed represented 12 prospective cohort studies (28;99;124-133) and 8 case-control studies (134-140). Four of these publications (137-140) pertained to different aspects of the same case-control study. The database represented by the 23 studies was large, including a total of 9,747 cases of colon cancer with approximately equal distribution between the sexes (4,933 in men and 4,814 in women). The studies were conducted in the United States (124-126;129;131;132;137-142), Europe (Denmark (28), Finland (99;127), Italy (143), Norway (133), Sweden (128) and Switzerland (136)), and Asia (China (134), Japan (130;135), and Taiwan (144)).

Overall, the studies consistently show an inverse association between physical activity and the risk of developing colon cancer, with 9 of the 12 cohort studies and 5 of the 8 case-control studies indicating significant, inverse associations with at least one domain of physical activity (e.g., occupational versus leisure-time) and/or in one sex. Across all the studies, the median RR, comparing most with least active subjects, was 0.7. More specifically, results were similar across the cohort studies (median RR = 0.8) and the case-control studies (median RR = 0.7), as well as for men and women (median RR in both sexes = 0.7). These findings, encompassing studies published in 1995 and later in the Physical Activity Guidelines for Americans Scientific Database, are comparable with findings from a recent review of the literature on physical activity and colon cancer risk that also included studies published before 1995 (145). In this recent review, the median RR, comparing most with least active subjects across all studies, also was 0.7 (median RR for men, 0.7; for women, 0.6).

For the prospective cohort studies, bias due to recall of physical activity is unlikely because physical activity was assessed before the development of colon cancer. Thus, any misclassification of physical activity is likely to be random, diluting associations rather than causing spurious inverse relations. The results also do not appear to be confounded by other factors associated with colon cancer risk because many studies adjusted their findings for several factors, including BMI, smoking, alcohol, diet (e.g., energy intake, intake of calcium and folate intake of fiber, vegetables, and meat), use of aspirin, screening, menopausal status and use of menopausal hormone therapy, and family history of colon cancer. In particular, the findings appear independent of BMI, with most cohort studies (9 of 12) (28;124;125;127-130;132;133) adjusting for this factor, and continuing to observe significant inverse associations. However, fewer than half the case-control studies (3 of 8) adjusted for BMI. Finally, the inverse associations observed are supported by plausible biologic mechanisms. Thus, although the data on physical activity and risk of developing colon cancer are based on observational epidemiologic studies, the inverse associations indicated by these studies are likely to be real.

Associations for Specific Subgroups

Several studies have examined whether the association between physical activity and decreased colon cancer risk varies, depending on use of menopausal hormone therapy (125;131), various aspects of diet (125;139), or BMI (125;128;130;134;138;142). The findings have been inconsistent, with the most consistent being the suggestion that the adverse impact of high BMI on colon cancer risk may be ameliorated by higher levels of physical activity (134;138;142).

Several studies also have examined whether physical activity has a different association with colon cancers occurring at different subsites of the colon. The data have been equivocal, with some studies suggesting a larger magnitude of association for cancers occurring in the proximal colon (130;136;142), while others have reported greater associations for cancers of the distal colon (128;132). Most studies, however, have observed equivalent associations or unclear differences across proximal and distal sites of the colon (125;126;131;133;135;140;143).

Dose-Response Pattern

All but one (99) of the studies classified subjects according to at least 3 levels of physical activity, allowing investigators to assess dose-response. In the cohort studies, 7 of 11 studies with at least 3 physical activity levels reported significant, inverse trends between physical activity and colon cancer risk (124;126-128;130;132;133). For the case-control studies, 4 of 8 also observed significant, inverse trends between activity level and colon cancer risk (134;136;143;144). As discussed above, because of the many different methods used to assess and classify physical activity in these studies, it is difficult to ascertain the shape of the dose-response curve, apart from noting that a dose-response relation appears likely.

Types and Amount of Physical Activity

Most studies have assessed leisure-time and/or occupational physical activity only, with one study also assessing active commuting, in the form of walking or bicycling to work (134). Because of the different questionnaires used to assess physical activity and the different categories used to group subjects in the studies, it is difficult to integrate the findings across the studies. Further, most studies presented their findings according to overall volume of energy expended, and data are sparse on specific kinds of activity associated with decreased colon cancer risk.

However, significantly lower risks of colon cancer have been observed with leisure-time physical activity (ordered in approximately ascending doses of physical activity) of at least twice a week for at least 10 minutes' duration (142), at least 4 hours per week of moderate-to-vigorous intensity recreational activity (131), at least 20 MET-hours per week of leisure-time activity (144), more than 21 MET-hours per week of leisure-time activity (132), 7 or more hours per week of recreational activities including walking (126) a median of 35.25 MET-hours per week of overall activity (130), a median of 46.8 MET-hours per week of leisure-time activity (124), and more than 94.3 MET-hours per week of active commuting (134). Additionally, the case-control study by Slattery and colleagues suggests that physical activity needs to be vigorous in intensity (137-140) to reduce colon cancer risk. Overall, these data suggest that 30 to 60 minutes per day of moderate-to-vigorous intensity physical activity may be needed to significantly lower the risk of developing colon cancer.

Rectal Cancer

In contrast to the associations observed between physical activity and colon cancer, the data on physical activity and risk of developing rectal cancer are far more mixed. More than half of the studies have reported no significant associations (99;126;130;133;143;144;146), with the remaining studies observing significantly lower risks (or of borderline significance) with higher levels of physical activity (127;128;135;136;140). In a recent review of the literature on physical activity and rectal cancer risk, the median relative risk, comparing most with least active subjects across all studies, was 1.0, indicating little association (130).

Additional Cancer Sites

The available evidence for an association of physical activity with reduced risk of lung, endometrial, ovarian, pancreatic, and other cancers is less complete than that for breast, prostate, colon, and rectal cancers. Therefore, the following sections present a general overview.

Lung Cancer

A review of the association of physical activity and lung cancer risk was included within a recently published book chapter (145). At the time of that review, 15 cohort studies and 6 case-control studies had been published, overall indicating a median of 20% reduced risk for lung cancer in the most versus the least active subjects. This present review focused on studies published between 1996 and 2006. Results indicate a 24% median reduction of lung cancer risk for the most versus least active subjects (101;147-156). As with the prior review, the reduction of risk was more obvious with case-control (median RR over 2 studies = 0.61) (154;156) than with cohort studies (median RR over 8 studies = 0.77) (101;147-153). The inverse relation of physical activity with lung cancer risk is similar for men (0.74, 8 studies since 1996) (101;147;149-153;156) and women (0.75, 6 studies since 1996) (147-149;152;154;156).

Most of the studies on the association of physical activity and lung cancer adjust for cigarette smoking. However, even with this adjustment, the potential for residual confounding is quite high. Three studies have reported risk reductions specifically for current smokers, former smokers, or never smokers (148;150;155). The risk reduction in these studies is more similar for current and former smokers (median RR of 0.61 (148;150;155) and 0.59 (148;150), respectively) than for never smokers (median RR of 1.03 for 2 studies reporting for this subgroup) (148;155). As yet, evidence is too sparse to conclude that the reduction of lung cancer risk by physical activity is isolated to current and former smokers.

The question of whether the association of physical activity with lung cancer is due to residual confounding by smoking has been addressed in 2 ways: examining consistency of association across histologic subtypes of lung cancer and exploring the association in never smokers. Smoking is more clearly established as a risk factor for some histologic subtypes of lung cancer than others. Evidence links smoking more closely to small cell and squamous cell lung cancers than to adenocarcinoma of the lung. Therefore, one indirect approach to the question of whether the association of physical activity with reduced risk for lung cancer is due to residual confounding by smoking status is to evaluate whether the association is present for all histologic subtypes, including adenocarcinoma. Three studies to date have examined whether the association of physical activity is similar across most lung cancer histologic subtypes, as well as within sex. In men, the median relative risks for lung cancer for those who are most versus least active are 0.59, 0.96, 0.80, and 0.73 for small cell, squamous cell, adenocarcinoma, and other/nonspecified histologic types, respectively (147;149;156). In women, the median RR values for most versus least active among the same subtypes are 0.81, 0.77, 0.86, and 0.56, respectively (147;148;156). This evidence suggests that the physical activity association is present across histologic subtypes, including adenocarcinoma. Another approach to determining whether the overall association of physical activity and lung cancer is due to residual confounding by smoking is to study non-smokers. The RR (or odds radio) for non-smokers was 1.32 and 0.74 in the one cohort and one case-control study to report an association specifically for non-smokers (148;155). It also should be noted that the 39% risk reduction for most versus least active current smokers pales in comparison to the reduction of risk from quitting smoking. Smoking cessation remains the most important means to reduce lung cancer risk among smokers. That stated, it would be of interest to understand better the potential mechanisms by which physical activity may assist in marginally reducing lung cancer risk among current and former smokers. To our knowledge, no research has directly addressed this question.

Endometrial Cancer

A review of the association of physical activity and endometrial cancer risk was included within a recently published book chapter (145). At the time of that review, 4 cohort studies and 11 case control studies had been published, overall indicating a median relative risk of 0.70 for the most versus the least active subjects. An update of that review, focusing on studies published since 1996 reported a similar median RR (0.70) for the 15 most recently published studies, which included 7 cohort studies and 8 case-control studies (157-171). Of these more recent studies, 5 include relative risks that are adjusted for multiple variables but not for BMI (157-160;171). The median RR of 0.73 for these studies is similar to the results after adjustment for BMI, which was 0.70. This is important because the effect of physical activity on body weight has been hypothesized to mediate the purported association of physical activity with reduction of risk of endometrial cancer.

Another factor that should be accounted for in analyses is menopausal hormone therapy, given the potential causal link between use of unopposed estrogen therapy and increased risk of endometrial cancer. For example, the median RR from the 3 case-control studies that adjusted for menopausal hormone therapy was 0.70 (165;168;170) (no cohort studies published to date have adjusted for this factor) compared to a median RR of 0.68 for the 10 case-control and cohort studies that did not adjust for menopausal hormone therapy (157-164;169;171).

Overall, evidence indicates an inverse association between physical activity and incidence of endometrial cancer. Further, the lack of change in the median relative risks for studies that did versus did not adjust for BMI or menopausal hormone therapy may indicate that the association is not mediated through obesity or the generally healthy lifestyle commonly associated with exogenous hormonal exposure.

Ovarian Cancer

The association of physical activity with incidence of ovarian cancer was explored in a meta-analysis and systematic review published late in 2007 (172). This review concluded that a modest inverse association exists, with a weighted pooled RR of 0.81 (95% confidence interval was 0.72-0.92). Sensitivity analyses indicated no difference of findings when summarized studies did versus did not adjust for BMI (which may be on the causal pathway) and for exogenous hormone use (e.g., oral contraceptives).

Pancreatic Cancer

A total of 8 cohort studies (173-180) and 2 case-control studies (181;182) have examined whether physical activity may reduce incidence of pancreatic cancer. Case-control studies may be particularly biased for pancreatic cancer, given that at diagnosis most patients have advanced disease, are symptomatic, and often have recent weight loss. Four of the 10 cited case-control studies of pancreatic cancer adjusted for BMI in multivariate models. In the 5 cohort studies that did not adjust for BMI (173-177), the median relative risk for the association of physical activity with pancreatic cancer incidence was 1.21. One of the case-control studies provided an odds ratio (OR = 0.78) for men that was not adjusted for BMI (182). Both of the case-control studies provided odds ratios for women that were not adjusted for BMI; the average of these was 0.82 (181;182). In spite of this inconsistent evidence, when taken in combination with the observation of a weak positive association with BMI (177;183), it remains possible that a level of physical activity sufficient for weight control would be associated with reduced incidence of pancreatic cancer.

Other Cancers

The potential for physical activity to reduce incidence of other cancers (e.g., thyroid, kidney, bladder, and hematopoietic) also has been studied. Reviews of these cancers are not included here because the data are too sparse to allow any conclusions regarding a potential relation with physical inactivity. Readers are referred to other reviews for an overview of results from these studies (2;145).

Question 2: What Are the Effects of Physical Activity on Cancer Survivors, Including Late and Long-Term Effects of Treatment, Quality of Life, and Prognosis?

Conclusions

A common definition of "cancer survivor" is any individual who has had a diagnosis of cancer, from the point of diagnosis and for the balance of life. Cancer survivors are a subset of the US adult population that is expected to grow substantively in the coming decades. As such, the role of physical activity in improving outcomes for cancer survivors is likely to increase in importance as well. Recently, data have been published regarding the effects of physical activity on health outcomes among persons who already have cancer. These studies suggest that physically active individuals with breast or colon cancer may have improved prognosis (i.e., fewer recurrences and deaths), compared with sedentary survivors. In addition, physical activity may play an important role in preventing, attenuating, or rehabilitating late and long-term effects of cancer treatment. Walking is a commonly prescribed form of exercise in the studies reviewed here and appears to have benefits on muscular strength and endurance, as well as quality of life. Dose-response effects and long-term outcomes are unknown for any outcomes from physical activity interventions in cancer survivors at this time.

Introduction

More than 10 million people in the United States are cancer survivors, and more than 16% of adults older than age 65 years are cancer survivors (184). The increasing success of cancer treatments has required a shift in focus toward new outcomes, such as preventing recurrence and mortality, and accommodating the unique medical and psychosocial needs of cancer survivors.

Cancer treatment typically includes some combination of surgery, radiation therapy, or chemotherapy, and may also include hormonal therapies, steroid treatment, immunotherapies, or monoclonal antibody treatment. Each of these therapies is associated with acute as well as late and long-term adverse physiologic and psychological effects. The terms "late effects" or "long-term effects" (185) are distinct in the timing of their onset. Late effects are side effects or complications that are absent or subclinical at the end of therapy but that emerge after compensatory systems fail or some second insult (e.g., deconditioning) occurs that results in a clinically significant diagnosis that can be traced back to effects of treatment. An example of a late effect would be the diagnosis of a cardiac arrhythmia years after treatment with a cardiotoxic chemotherapeutic agent such as adriamyacin (186). Long-term effects are adverse effects or complications that appear during treatment and persist long afterward, for months, years, or the duration of life. Physical activity could be useful for preventing or attenuating some late and long-term effects of cancer treatments (Figure G7-1) (187), and may also be useful for prevention of recurrence or cancer mortality among cancer survivors.

Figure G7.1. Late and Long-Term Effects of Cancer Treatment That May Be Positively Affected by Physical Activity

Figure G7.1. Late and Long-Term Effects of Cancer Treatment That May Be Positively Affected by Physical Activity. A text-only table follows this graphic.

Cancer Treatment: Physical Changes: Psychological and Behavioral Changes:
Surgery
Radiation
Chemotherapy
Immunotherapy
Hormone therapy
Steroid therapy 		↓pulmonary function
↓cardiac function
↓muscle mass
↑fat mass
↑weight or BMI
↓decreased muscle strength/power
↑inflammation
↓immune function
↓bone health
↑trauma and scarring
↓lymphatic function (lymphedema) 		↓exercise/physical activity
↑physical symptoms and pain
↑depression
↓cognitive function
↓quality of life (multiple domains)

The acute effects of treatment and the potential for positive effects of physical activity during active cancer treatment are beyond the scope of this review, but have been reviewed elsewhere (188;189). Also not reviewed here are the late or long-term effects of childhood cancer treatment, as little research has been conducted in this area.

Rationale

Effects of Physical Activity on Cancer Recurrence and Mortality

Though few studies have been conducted on the role of physical activity in preventing cancer recurrence or reducing mortality, the consistent findings of a preventive effect warrants comment. Data from the Nurses' Health Study were used to explore the dose-response association of physical activity with overall and breast cancer specific mortality, as well as recurrence, among 2,987 breast cancer survivors over a median of 96 months of follow-up (190). The results indicated a 29% decrease in overall mortality among women who did at least 3 MET-hours per week of aerobic activity after diagnosis, with minimal additional protection from greater levels of physical activity. The decrease in breast cancer-specific mortality and recurrence were 50% and 43%, respectively, in women who engaged in at least 9 MET-hours per week of physical activity compared with women who did less than 3. Additional benefits were small for activity levels greater than 9 MET-hours per week, which can be translated to 3 hours per week of walking at 2.5 miles per hour. Considerable evidence indicates that overweight, obesity, and weight gain are associated with breast cancer recurrence (191-193). These results are consistent with the hypothesis that physical activity reduces risk of mortality or recurrence among breast cancer survivors through weight control.

Evidence for a role of physical activity in colon and colorectal cancer survivorship comes from 2 recently published observational studies. One of these, the Nurses' Health Study, observed an inverse dose-response association of physical activity and overall and colorectal cancer-specific mortality in 554 women who had had a previous diagnosis of colorectal cancer. Women who engaged in at least 18 MET-hours per week of physical activity after diagnosis had a 61% and 57% reduced risk of colorectal cancer-specific and overall mortality, respectively, compared to women who did less than 3 MET-hours per week (194). A dose-response association of physical activity and colon cancer disease-free survival also was seen in the cohort of 832 male and female patients who participated in the CALBG trial (195). In this latter cohort, 18 MET-hours per week, or 6 hours of walking per week at 2.5 miles per hour, was associated with a 49% reduction in risk of recurrence (195).

Effects of Exercise on Prevention of Long-Term or Late Effects of Cancer Treatment

A number of recent systematic reviews (188;196-205) as well as 2 meta-analyses (188;206) have recently been conducted on the effects of physical activity interventions on a variety of outcomes in cancer survivors. Readers interested in an in-depth discussion of the effects of exercise on cancer survivors are guided to these reviews. Below, the effects of exercise training on late or long-term effects is reviewed for outcomes for which there is the greatest amount of evidence and consensus and that may be most useful in guiding quantitative or qualitative behavioral recommendations for cancer survivors. Of the 22 controlled clinical trials published since 1995 and reviewed here, only 1 (207), examined a dose-response pattern of exercise training on any outcome, and none was noted. For each of the outcomes reviewed below, effects of walking programs are noted, if such data were available. Most of the studies reviewed were relatively short in duration (6 months or less); long-term effects are not yet known.

Physiologic Effects

Cardiorespiratory Fitness. Though the effect of physical activity on cardiorespiratory fitness has been long established (see Part G. Section 2: Cardiorespiratory Health for a detailed discussion of this topic), it is of particular relevance for cancer survivors given the cardiotoxic effects of several commonly used cancer treatment drugs and radiation to the chest (186;208). A meta-analysis published in 2005 indicated a strong weighted mean effect size of 0.65 (P=0.003) for cardiorespiratory fitness based on the 4 exercise interventions that had assessed this outcome in cancer survivors after treatment (188). Since this meta-analysis, 9 additional RCTs have assessed whether various of exercise interventions in cancer survivors improve cardiorespiratory fitness after treatment (209-217). All 13 studies have shown positive effects, and 11 showed statistically significant improvements on cardiorespiratory function tests ranging from a 6-minute walk test to maximal treadmill or cycle ergometer tests. All of these studies included breast cancer survivors, and most included only breast cancer survivors. Fitness improvements have been demonstrated in a variety of programs, including walking, yoga, tai chi chuan, exercise at home, and exercise at fitness facilities. For most of the studies, exercise doses used were 3 weekly sessions of 20 to 40 minutes in duration at moderate intensity.

Muscular Strength and Endurance. Observational evidence in small convenience-sample studies suggests that muscle mass may decrease and fat mass may increase after some breast cancer chemotherapy regimens (218). Cancer treatment may result in a decrease in activity (219), with subsequent deconditioning associated with muscle disuse. Therefore, it is important to determine whether exercise training improves muscular strength or endurance in cancer survivors. Six studies have examined the effects of some form of resistance training, tai chi chuan, or yoga on muscle strength or endurance (211-213;215;220;221). All of these studies were conducted in women who had completed breast cancer treatment. Five observed positive effects of training (211;213;215;220;221) and 4 reported statistically significant improvements (211;213;215;220) in strength or endurance tests.

Flexibility. Cancer surgeries may result in decreased range of motion with scarring or tissue trauma, and these changes may result in altered physical function. Six studies have examined the effects of exercise training on flexibility. Three assessed effects of aerobic exercise or yoga on lower body flexibility with the sit-and-reach test in breast and colon cancer survivors (207;215;222). All 3 showed improvements in flexibility, but only one (207) observed a statistically significant improvement comparing changes between treatment and control participants. Three other studies examined effects of tai chi chuan, dance and movement, or aerobic exercise and stretching on shoulder range of motion in breast cancer survivors (211;223;224). All 3 noted improvements, and 2 noted significant between-group differences in shoulder range of motion (211;223).

Lymphedema. Surgical removal or irradiation of lymph nodes results in damage to the lymphatic system that can result in an inability of the affected body part to manage fluid balance and temperature regulation. This damage may impair immune response and wound healing, as well as response to trauma or injury. Swelling and pain in the affected body part can develop immediately after surgery and/or radiation or years later, making lymphedema a long-term risk among several types of survivors, including those with breast, head and neck, melanoma, genital cancers, lower gastrointestinal tract and bladder cancers. Lymphedema is considered a chronic condition, and occurs in 6% to 50% of breast cancer survivors, depending on number of nodes removed and intensity of radiation (225-227). Lower-limb lymphedema also occurs in 20% to 30% of cancer patients who have had lymph node removal or radiation in the groin or retroperitoneal lymph nodes (228-237). Four studies have examined the risk of lymphedema onset or worsening among breast cancer survivors by measuring changes in arm circumferences or symptoms resulting from exercise training (217;221;224;238). None of these studies has noted negative effects of aerobic or resistance exercise on arm circumferences or symptoms; evidence of possible benefit to the affected limb has not been examined. No studies of the safety or efficacy of exercise for cancer survivors with or at risk for lymphedema for cancer sites other than breast have been conducted.

Weight Change. Some breast cancer patients gain weight after diagnosis, and the associated changes in body composition may include decreased muscle mass and increased body fat, as suggested by a few convenience-sample studies (218). These effects have not been examined in population-based or clinical trial series of patients, nor in patients with other cancers. However, it is important to determine the effects of exercise training on body weight and body composition in survivors who have had any type of cancer treatment. The results of the 13 identified controlled trials conducted since 1995 indicate that, as for the general population, exercise may decrease percent body fat to a small degree, but has little to no effect on body weight in the absence of concurrent caloric restriction (188;207;210-215;217;222;239-241). (See Part G. Section 4: Energy Balance, for a detailed discussion of the association between physical activity, weight loss, and changes in body composition.)

Psychosocial and Symptom Effects

Quality of Life. The effect of exercise on health-related quality of life was examined in a systematic review and meta-analysis published in 2005 (188). This review concluded that evidence was strong for a positive effect of physical activity on quality of life in cancer survivors, though the weighted mean effect size of 0.30 was not statistically significant. Since the publication of that meta-analysis, an additional 10 studies have examined effects of physical activity on cancer survivors after treatment (209;213-217;223;224;240;242). Of these, all showed positive effects, and 8 indicated a statistically significant improvement in at least one quality of life indicator after a physical activity intervention. Overall, 10 out of 13 identified studies showed statistically significant improvements in quality of life resulting from a physical activity intervention after cancer treatment.

Fatigue. Cancer-related fatigue is distinct from ordinary types of fatigue in its persistence and severity (243). The effects of physical activity interventions on fatigue in cancer survivors (primarily breast cancer) have been tested in 8 studies since 1995. Of these 8 trials (207;209;210;214;216;222;239;244), 3 reported statistically significant improvements in fatigue after a program of aerobic exercise, walking, or cycling. Five other studies, most of which focused on walking programs among breast cancer survivors during the time period after treatment, observed improvements, but not statistically significant improvements. The mechanisms through which physical activity may improve cancer-related fatigue are not yet fully understood (243).

Question 3: What Mechanisms Explain the Associations Between Physical Activity and Cancer?

Conclusions

A number of plausible mechanisms might explain the associations between physical activity and cancer risk and prognosis. Increased physical activity reduces adiposity, which may explain reductions in cancers that are associated with overweight and obesity, including postmenopausal breast, colon, endometrial, and other cancers. Increased physical activity is associated with reduced levels of sex hormones, which may explain a link between physical activity and hormone-related cancers such as breast and endometrial cancers. Another possible mechanism is through the effect of physical activity and inflammation and immune function. Finally, increased physical activity reduces insulin resistance, which could explain associations with risk for some cancers, such as colon cancer, that may be increased in individuals with insulin resistance or hyperinsulinemia.

Rationale

Physical activity could affect cancer risk or progression through several plausible mechanisms (245). Many of these mechanisms may act through the effects of physical activity on obesity, with resulting changes to circulating levels of adipokines, cytokines, insulin, and sex hormones. Other mechanisms may involve direct effects on target organs and tissues. The effects of physical activity on carcinogenesis or prognosis are likely to be multi-factorial and may be affected by many factors such as age, sex, and adiposity, in addition to physical activity specific factors such as type, duration, frequency, and intensity of physical activity.

Menstrual Factors and Sex Steroid Hormones

Several modifiable menstrual factors increase breast cancer risk, including early age at menarche, frequent ovulation, regular cycles, and late age at menopause (246). Women with elevated levels of estrogens and androgens have increased risk of developing breast cancer. In a combined analysis of 9 large cohort studies, postmenopausal women in the top quintile for various estrogens or androgens had approximately double the risk of developing breast cancer compared with women in the lowest quintile (247). Elevated levels of estradiol or testosterone in premenopausal women increase risk of breast cancer as well (248;249). Medications that block estrogen receptors or that prevent estrogen production in peripheral tissues have been a mainstay of treatment for women with estrogen receptor positive breast cancer (250). Women with elevated estrogen concentrations (unopposed by progesterone) are at an increased risk for endometrial cancer (251). In men, anti-androgen therapy improves prostate cancer survival (252) and reduces overall incidence of the disease when tested as a preventive agent (253). However, recent evidence suggests that blood levels of androgens or estrogens are not related to prostate cancer risk (247), suggesting that only prostatic levels of sex hormones are relevant for prostate carcinogenesis or progression.

Premenopausal Women

The effect of physical activity on age at menarche, menstrual cycle function, and level of ovarian-produced sex steroid hormone levels in girls and young women are potential mechanisms for reduced breast cancer risk (254). Moderate-intensity physical activity may cause small changes in reproductive hormones in premenopausal women, but high intensity or volume of exercise sufficient to cause a negative energy balance may be required to induce menstrual dysfunction (amenorrhea, anovular cycles and luteal phase deficiency) with significantly decreased production of ovarian estradiol and progesterone (255-263).

Postmenopausal Women

In postmenopausal women, increased physical activity has been associated with decreased serum concentrations of estradiol, estrone, and androgens (264-266). The positive effect of physical activity is closely linked to body composition because the primary source of estrogen in postmenopausal women is from aromatization of androgen precursors in peripheral, mainly adipose, tissue. In a sub-sample from the Women's Health Initiative (WHI) Dietary Modification Trial, women with low self-reported physical activity had higher levels of estrone, estradiol, and free estradiol, and lower levels of sex-hormone binding globulin (which binds estradiol, making less available to target tissue) than did active women (265). The highest levels of estrogen were observed in women who were both below the median level for physical activity (i.e., less than 6.5 MET-hours per week, approximately less than 1.5 hours per week of brisk walking) and above the median BMI (i.e., at least 29 kg/m2).

In an RCT, 173 overweight, sedentary postmenopausal women were assigned to a moderate-intensity aerobic exercise, 45 minutes per day, 5 days per week for 12 months or to a control group. A significant decrease in estradiol, estrone, and free estradiol was seen from baseline to 3 months in exercisers versus controls, with an attenuation of the effect at 12 months (267). However, in those women who lost body fat, the exercise intervention resulted in a statistically significant reduction in these estrogens at both 3 and 12 months. Similarly, in women who lost body fat, a statistically significant decrease in testosterone and free testosterone occurred in exercisers compared with controls (268). These intervention and observational studies results suggest that both increased physical activity and reduced body fat will produce the greatest protection against breast cancer by producing the greatest decrease in serum sex hormones.

Men

Chronically lowered testosterone concentrations have been reported in athletes, but this finding may require a threshold amount or intensity of physical activity to occur (269), and the effects of moderate-intensity aerobic exercise on sex steroid hormones in men is not known. In a recent trial, 102 men aged 40 to 75 years were randomly assigned to a 12-month moderate to vigorous intensity aerobic exercise intervention (60 minutes per day, 6 days per week) or a control group (no change in activity) (270). Dihydrotestosterone (DHT) increased 14.5% in exercisers compared to 1.7% in controls at 3 months (P=0.04). At 12 months, DHT remained 8.6% above baseline in exercisers versus a 3.1% decrease in controls (P=0.03). Sex hormone binding globulin increased 14.3% in exercisers versus 5.7% in controls at 3 months (P=0.04), while at 12 months it remained 8.9% above baseline in exercisers compared to 4.0% in controls (P=0.13). No statistically significant differences were observed for testosterone, free testosterone, 3α-Diol-G, estradiol, or free estradiol in exercisers versus controls. Therefore, the association of physical activity with circulating hormone levels in men is still unclear.

Metabolic and Other Hormones

Insulin resistance has been linked to increased risk of breast, colon, pancreas, endometrial and stomach cancers (271). Higher cancer incidence and mortality also have been noted in those with type 2 diabetes or impaired glucose tolerance (271;272). Insulin can enhance tumor development by stimulating cell proliferation or inhibiting apoptosis (271). It also can regulate the synthesis and biological availability of sex steroid hormones, and inhibit hepatic synthesis of sex hormone binding globulin (271). Acute bouts of physical activity improve insulin sensitivity and increase glucose uptake by skeletal muscle for up to 12 hours (273), and chronic exercise training results in prolonged improvements in insulin sensitivity (274-276). Although body composition has been strongly associated with insulin sensitivity, exercise-induced changes in insulin sensitivity can occur from physical activity, independent of the changes in weight or body composition (273;274;277). An additive effect of resistance training to improve insulin sensitivity and glycemic control also has been proposed because skeletal muscle is a primary site of insulin resistance (273;278).

Women with elevated levels of prolactin are at increased risk of breast cancer (279), and a recent clinical trial found that increased physical activity levels as measured by increased VO2max over 1 year in a moderate-intensity exercise intervention was associated with statistically significant reductions in prolactin levels in postmenopausal, overweight women (280).

Inflammation

Elevated levels of pro-inflammatory factors, such as C-reactive protein (CRP), interleukin (IL)-6, tumor-necrosis factor-α (TNF-α), and decreased levels of anti-inflammatory factors, such as adiponectin, have been linked with increased cancer risk (281). Physical activity may reduce systemic inflammation alone or in combination with body weight or composition through reducing macrophage or adipose cell production of inflammatory cytokines in adipose tissue, although exact mechanisms are unknown (278;282).

Although cross-sectional studies support an association between chronic physical activity and lower levels of the inflammatory markers CRP, serum amyloid A (SAA), IL-6 and TNF-α in both men and women, intervention studies of exercise alone or exercise and diet combined have had inconsistent results, with some studies but not others showing reductions in these inflammatory markers (282).

Increases in adiponectin have been seen with physical activity interventions in the presence of significant weight loss (283). Shorter duration prospective physical activity and weight loss interventions have failed to alter adiponectin levels despite modest changes in body weight and body composition (278).

Immune Function

The immune system is thought to play a role in reducing cancer risk by recognizing and eliminating abnormal cells or through acquired and/or innate immune system components (284). The role of physical activity on immune factors related to cancer has been largely untested, but one hypothesis is that physical activity could improve the number or function of natural killer cells, which play a role in tumor suppression (282).

Bouts of physical activity have been shown to result in acute increases in a number of components of immune function (e.g., neutrophils, monocytes, eosinophils, and lymphocytes), followed by a dip below pre-exercise levels lasting up to 1 to 3 hours (285). For chronic physical activity, an inverted J-shaped dose-response relation between intensity of physical activity and immune function has been shown. Moderate physical activity results in enhanced immune function, but exhaustive exercise, overtraining, or high-intensity exercise may lead to immunosuppression, which may result in increased susceptibility to ailments such as upper respiratory infections (282). However, the current evidence on moderate-intensity physical activity from randomized controlled trials is inconclusive, with differences in components of the innate immune system noted in some, but not all, cross sectional studies that compare exercisers to non-exercisers. Randomized controlled trials of moderate physical activity show little effect on immune function (282).

Other Mechanisms

Physical activity also could mediate cancer risk through additional mechanisms, such as its effects on other body structures. For example, physical activity affects colon motility, leading to decreased transit time and, perhaps, reduced carcinogen exposure in the colon (254). In addition, physical activity has been hypothesized to affect various tissues leading to reduced carcinogenic prostaglandin (PG) production (286), although an RCT found no effect of a 12-month aerobic exercise intervention (1 hour per day, 6 day per week) on colon mucosal prostaglandins PGE2 or PGF2alpha in 202 men or women aged 40 to 75 years (287).

Overall Summary and Conclusions

Increased physical activity is associated with reduced risk of several cancers. Most evidence for this association is available for breast and colon cancers, although growing evidence suggests an association between increased physical activity and reduced risk of endometrial and lung cancers. Overall, data suggest that 30 to 60 minutes per day of moderate-to-vigorous intensity physical activity may be needed to significantly lower the risk of developing breast and colon cancers. The effect of physical activity is larger for colon cancer (median reduction in risk of 30% across reviewed studies) compared with breast cancer (median reduction in risk of 20% across studies). A large part of the effect of physical activity on cancer is likely mediated through obesity and other hormonal and metabolic mechanisms. Randomized controlled trials have demonstrated effects of physical activity interventions on cancer risk factors, which further support a role of physical activity in reducing risk for cancer.

Strong evidence links increased physical activity in cancer survivors with improved quality of life and increased fitness. Less evidence is available regarding the effect of physical activity on cancer recurrence and survival. A 2006 publication from the American Cancer Society (3) states that although the current public health guidelines of 30 to 60 minutes of moderate-intensity aerobic exercise 5 times per week have not been studied systematically in cancer survivors, there is no reason to think that this would not also benefit survivors. Overall, results indicate that guidelines for cardiovascular exercise for cancer survivors who have completed treatment need not be different from those of the general population, and that particular physiologic and psychosocial effects of cancer and its treatments are positively affected by cardiovascular exercise, resistance training, and flexibility training.

Research Needs

Knowledge about the role of physical activity in reducing the risk of common cancers would benefit from additional evidence gathered from clinical trials. In the survivorship setting, clinical trials showing a benefit of physical activity interventions on reducing deaths, recurrences, and reducing the impact of late or long-term treatment effects, also would make a valuable contribution to our understanding of the needs of this growing population.

Other research needs include studies to clarify biological mechanisms linking physical activity to specific cancers in order to identify associations with less commonly studied cancers, define the shape of dose-response curve of the physical activity-cancer relation, determine the effect of low-intensity activities and accumulated bouts, and assess the effect of physical activity within specific population subgroups.

Additional observational epidemiologic research to identify the dose, type, and frequency of physical activity on risk of various cancer sites and subtypes is needed, in addition to identifying the effect of physical activity on risk of specific cancers within particular population subgroups including various race/ethnic, age, sex, and groups at elevated risk of cancer.

Reference List

  1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ. Cancer statistics, 2008. CA Cancer J.Clin. 2008 Mar;58(2):71-96.
  2. Vainio H, Bianchini F, International Agency for Research on Cancer. Weight control and physical activity. Lyon: IARC Press; 2002.
  3. Doyle C, Kushi LH, Byers T, Courneya KS, mark-Wahnefried W, Grant B, McTiernan A, Rock CL, Thompson C, Gansler T, et al. Nutrition and physical activity during and after cancer treatment: an American Cancer Society guide for informed choices. CA Cancer J.Clin. 2006 Nov;56(6):323-53.
  4. Thune I, Furberg AS. Physical activity and cancer risk: dose-response and cancer, all sites and site-specific. Med.Sci.Sports Exerc. 2001 Jun;33(6 Suppl):S530-S550.
  5. Lee IM. Physical activity and cancer prevention--data from epidemiologic studies. Med.Sci.Sports Exerc. 2003 Nov;35(11):1823-7.
  6. Friedenreich CM. Physical activity and prostate cancer risk. In: McTiernan A, editor. Cancer prevention and management through exercise and weight control. Boca Raton: CRC Press; 2006. p. 91-120.
  7. Slattery ML. Physical activity and colorectal cancer. In: McTiernan A, editor. Cancer prevention and management through exercise and weight control. Boca Raton: CRC Press; 2006. p. 75-90.
  8. Patel AV, Bernstein L. Physical activity and cancer incidence: breast cancer. In: McTiernan A, editor. Cancer prevention and management through exercise and weight control. Boca Raton: CRC Press; 2006. p. 49-74.
  9. Dorgan JF, Brown C, Barrett M, Splansky GL, Kreger BE, D'Agostino RB, Albanes D, Schatzkin A. Physical activity and risk of breast cancer in the Framingham Heart Study. Am.J.Epidemiol. 1994 Apr 1;139(7):662-9.
  10. Fraser GE, Shavlik D. Risk factors, lifetime risk, and age at onset of breast cancer. Ann.Epidemiol. 1997 Aug;7(6):375-82.
  11. Thune I, Brenn T, Lund E, Gaard M. Physical activity and the risk of breast cancer. N.Engl.J.Med. 1997 May 1;336(18):1269-75.
  12. Cerhan JR, Chiu BC-H, Wallace RB, Lemke JH, Lynch CF, Torner JC, Rubenstein LM. Physical activity, physical function, and the risk of breast cancer in a prospective study among elderly women. J.Gerontol.A.Biol.Sci.Med.Sci. 1998 Jul;53(4):M251-m256.
  13. Sesso HD, Paffenbarger RS, Jr., Lee IM. Physical activity and breast cancer risk in the College Alumni Health Study (United States). Cancer Causes Control 1998 Aug;9(4):433-9.
  14. Rockhill B, Willett WC, Hunter DJ, Manson JE, Hankinson SE, Colditz GA. A prospective study of recreational physical activity and breast cancer risk. Arch.Intern.Med. 1999 Oct 25;159(19):2290-6.
  15. Wyshak G, Frisch RE. Breast cancer among former college athletes compared to non-athletes: a 15-year follow-up. Br.J.Cancer 2000 Feb;82(3):726-30.
  16. Moore DB, Folsom AR, Mink PJ, Hong CP, Anderson KE, Kushi LH. Physical activity and incidence of postmenopausal breast cancer. Epidemiology 2000 May;11(3):292-6.
  17. Dirx MJ, Voorrips LE, Goldbohm RA, van den Brandt PA. Baseline recreational physical activity, history of sports participation, and postmenopausal breast carcinoma risk in the Netherlands Cohort Study. Cancer 2001 Sep 15;92(6):1638-49.
  18. Lee IM, Rexrode KM, Cook NR, Hennekens CH, Burin JE. Physical activity and breast cancer risk: the Women's Health Study (United States). Cancer Causes Control 2001 Feb;12(2):137-45.
  19. Luoto R, Latikka P, Pukkala E, Hakulinen T, Vihko V. The effect of physical activity on breast cancer risk: a cohort study of 30,548 women. Eur.J.Epidemiol. 2000;16(10):973-80.
  20. Breslow RA, Ballard-Barbash R, Munoz K, Graubard BI. Long-term recreational physical activity and breast cancer in the National Health and Nutrition Examination Survey I epidemiologic follow-up study. Cancer Epidemiol.Biomarkers Prev. 2001 Jul;10(7):805-8.
  21. Moradi T, Adami HO, Ekbom A, Wedren S, Terry P, Floderus B, Lichtenstein P. Physical activity and risk for breast cancer a prospective cohort study among Swedish twins. Int.J.Cancer 2002 Jul 1;100(1):76-81.
  22. Patel AV, Callel EE, Bernstein L, Wu AH, Thun MJ. Recreational physical activity and risk of postmenopausal breast cancer in a large cohort of US women. Cancer Causes Control 2003 Aug;14(6):519-29.
  23. Colditz GA, Feskanich D, Chen WY, Hunter DJ, Willett WC. Physical activity and risk of breast cancer in premenopausal women. Br.J.Cancer 2003 Sep 1;89(5):847-51.
  24. McTiernan A, Kooperberg C, White E, Wilcox S, Coates R, ms-Campbell LL, Woods N, Ockene J. Recreational physical activity and the risk of breast cancer in postmenopausal women: the Women's Health Initiative Cohort Study. JAMA 2003 Sep 10;290(10):1331-6.
  25. Margolis KL, Mucci L, Braaten T, Kumle M, Trolle LY, Adami HO, Lund E, Weiderpass E. Physical activity in different periods of life and the risk of breast cancer: the Norwegian-Swedish Women's Lifestyle and Health cohort study. Cancer Epidemiol.Biomarkers Prev. 2005 Jan;14(1):27-32.
  26. Silvera SA, Jain M, Howe GR, Miller AB, Rohan TE. Energy balance and breast cancer risk: a prospective cohort study. Breast Cancer Res.Treat. 2006 May;97(1):97-106.
  27. Rintala P, Pukkala E, Laara E, Vihko V. Physical activity and breast cancer risk among female physical education and language teachers: a 34-year follow-up. Int.J.Cancer 2003 Nov 1;107(2):268-70.
  28. Schnohr P, Gronbaek M, Petersen L, Hein HO, Sorensen TI. Physical activity in leisure-time and risk of cancer: 14-year follow-up of 28,000 Danish men and women. Scand.J.Public Health 2005;33(4):244-9.
  29. Bardia A, Hartmann LC, Vachon CM, Vierkant RA, Wang AH, Olson JE, Sellers TA, Cerhan JR. Recreational physical activity and risk of postmenopausal breast cancer based on hormone receptor status. Arch.Intern.Med. 2006 Dec 11;166(22):2478-83.
  30. Mertens AJ, Sweeney C, Shahar E, Rosamond WD, Folsom AR. Physical activity and breast cancer incidence in middle-aged women: a prospective cohort study. Breast Cancer Res.Treat. 2006 May;97(2):209-14.
  31. Chang SC, Ziegler RG, Dunn B, Stolzenberg-Solomon R, Lacey JV, Jr., Huang WY, Schatzkin A, Reding D, Hoover RN, Hartge P, et al. Association of energy intake and energy balance with postmenopausal breast cancer in the prostate, lung, colorectal, and ovarian cancer screening trial. Cancer Epidemiol.Biomarkers Prev. 2006 Feb;15(2):334-41.
  32. Tehard B, Friedenreich CM, Oppert JM, Clavel-Chapelon F. Effect of physical activity on women at increased risk of breast cancer: results from the E3N cohort study. Cancer Epidemiol.Biomarkers Prev. 2006 Jan;15(1):57-64.
  33. Lahmann PH, Friedenreich C, Schuit AJ, Salvini S, Allen NE, Key TJ, Khaw KT, Bingham S, Peeters PH, Monninkhof E, et al. Physical activity and breast cancer risk: the European Prospective Investigation into Cancer and Nutrition. Cancer Epidemiol.Biomarkers Prev. 2007 Jan;16(1):36-42.
  34. Dallal CM, Sullivan-Halley J, Ross RK, Wang Y, Deapen D, Horn-Ross PL, Reynolds P, Stram DO, Clarke CA, nton-Culver H, et al. Long-term recreational physical activity and risk of invasive and in situ breast cancer: the California teachers study. Arch.Intern.Med. 2007 Feb 26;167(4):408-15.
  35. Bernstein L, Henderson BE, Hanisch R, Sullivan-Halley J, Ross RK. Physical exercise and reduced risk of breast cancer in young women. J.Natl.Cancer Inst. 1994 Sep 21;86(18):1403-8.
  36. Friedenreich CM, Rohan TE. Physical activity and risk of breast cancer. Eur.J.Cancer Prev. 1995 Apr;4(2):145-51.
  37. McTiernan A, Stanford JL, Weiss NS, Daling JR, Voigt LF. Occurrence of breast cancer in relation to recreational exercise in women age 50-64 years. Epidemiology 1996 Nov;7(6):598-604.
  38. Chen CL, White E, Malone KE, Daling JR. Leisure-time physical activity in relation to breast cancer among young women (Washington, United States). Cancer Causes Control 1997 Jan;8(1):77-84.
  39. Hu YH, Nagata C, Shimizu H, Kaneda N, Kashiki Y. Association of body mass index, physical activity, and reproductive histories with breast cancer: a case-control study in Gifu, Japan. Breast Cancer Res.Treat. 1997 Mar;43(1):65-72.
  40. Gammon MD, Schoenberg JB, Britton JA, Kelsey JL, Coates RJ, Brogan D, Potischman N, Swanson CA, Daling JR, Stanford JL, et al. Recreational physical activity and breast cancer risk among women under age 45 years. Am.J.Epidemiol. 1998 Feb 1;147(3):273-80.
  41. Ueji M, Ueno E, Osei-Hyiaman D, Takahashi H, Kano K. Physical activity and the risk of breast cancer: a case-control study of Japanese women. J.Epidemiol. 1998 Jun;8(2):116-22.
  42. Marcus PM, Newman B, Moorman PG, Millikan RC, Baird DD, Qaqish B, Sternfeld B. Physical activity at age 12 and adult breast cancer risk (United States). Cancer Causes Control 1999 Aug;10(4):293-302.
  43. Verloop J, Rookus MA, van der KK, van Leeuwen FE. Physical activity and breast cancer risk in women aged 20-54 years. J.Natl.Cancer Inst. 2000 Jan 19;92(2):128-35.
  44. Moradi T, Nyren O, Zack M, Magnusson C, Persson I, Adami HO. Breast cancer risk and lifetime leisure-time and occupational physical activity (Sweden). Cancer Causes Control 2000 Jul;11(6):523-31.
  45. Shoff SM, Newcomb PA, Trentham-Dietz A, Remington PL, Mittendorf R, Greenberg ER, Willett WC. Early-life physical activity and postmenopausal breast cancer: effect of body size and weight change. Cancer Epidemiol.Biomarkers Prev. 2000 Jun;9(6):591-5.
  46. Adams-Campbell LL, Rosenberg L, Rao RS, Palmer JR. Strenuous physical activity and breast cancer risk in African-American women. J.Natl.Med.Assoc. 2001 Jul;93(7-8):267-75.
  47. Matthews CE, Shu XO, Jin F, Dai Q, Hebert JR, Ruan ZX, Gao YT, Zheng W. Lifetime physical activity and breast cancer risk in the Shanghai Breast Cancer Study. Br.J.Cancer 2001 Apr 6;84(7):994-1001.
  48. Friedenreich CM, Bryant HE, Courneya KS. Case-control study of lifetime physical activity and breast cancer risk. Am.J.Epidemiol. 2001 Aug 15;154(4):336-47.
  49. Gilliland FD, Li YF, Baumgartner K, Crumley D, Samet JM. Physical activity and breast cancer risk in hispanic and non-hispanic white women. Am.J.Epidemiol. 2001 Sep 1;154(5):442-50.
  50. Lee IM, Cook NR, Rexrode KM, Buring JE. Lifetime physical activity and risk of breast cancer. Br.J.Cancer 2001 Sep 28;85(7):962-5.
  51. Carpenter CL, Ross RK, Paganini-Hill A, Bernstein L. Effect of family history, obesity and exercise on breast cancer risk among postmenopausal women. Int.J.Cancer 2003 Aug 10;106(1):96-102.
  52. Dorn J, Vena J, Brasure J, Freudenheim J, Graham S. Lifetime physical activity and breast cancer risk in pre- and postmenopaus">al women. Med.Sci.Sports Exerc. 2003 Feb;35(2):278-85.
  53. John EM, Horn-Ross PL, Koo J. Lifetime physical activity and breast cancer risk in a multiethnic population: the San Francisco Bay area breast cancer study. Cancer Epidemiol.Biomarkers Prev. 2003 Nov;12(11 Pt 1):1143-52.
  54. Patel AV, Press MF, Meeske K, Calle EE, Bernstein L. Lifetime recreational exercise activity and risk of breast carcinoma in situ. Cancer 2003 Nov 15;98(10):2161-9.
  55. Steindorf K, Schmidt M, Kropp S, Chang-Claude J. Case-control study of physical activity and breast cancer risk among premenopausal women in Germany. Am.J.Epidemiol. 2003 Jan 15;157(2):121-30.
  56. Yang D, Bernstein L, Wu AH. Physical activity and breast cancer risk among Asian-American women in Los Angeles: a case-control study. Cancer 2003 May 15;97(10):2565-75.
  57. Taioli E, Barone J, Wynder EL. A case-control study on breast cancer and body mass. The American Health Foundation--Division of Epidemiology. Eur.J.Cancer 1995;31A(5):723-8.
  58. Mezzetti M, La VC, Decarli A, Boyle P, Talamini R, Franceschi S. Population attributable risk for breast cancer: diet, nutrition, and physical exercise. J.Natl.Cancer Inst. 1998 Mar 4;90(5):389-94.
  59. Levi F, Pasche C, Lucchini F, La VC. Occupational and leisure time physical activity and the risk of breast cancer. Eur.J.Cancer 1999 May;35(5):775-8.
  60. Hirose K, Hamajima N, Takezaki T, Miura S, Tajima K. Physical exercise reduces risk of breast cancer in Japanese women. Cancer Sci. 2003 Feb;94(2):193-9.
  61. Coogan PF, Newcomb PA, Clapp RW, Trentham-Dietz A, Baron JA, Longnecker MP. Physical activity in usual occupation and risk of breast cancer (United States). Cancer Causes Control 1997 Jul;8(4):626-31.
  62. Kumar NB, Riccardi D, Cantor A, Dalton K, Allen K. A case-control study evaluating the association of purposeful physical activity, body fat distribution, and steroid hormones on premenopausal breast cancer risk. Breast J. 2005 Jul;11(4):266-72.
  63. Malin A, Matthews CE, Shu XO, Cai H, Dai Q, Jin F, Gao YT, Zheng W. Energy balance and breast cancer risk. Cancer Epidemiol.Biomarkers Prev. 2005 Jun;14(6):1496-501.
  64. Friedenreich CM, Courneya KS, Bryant HE. Influence of physical activity in different age and life periods on the risk of breast cancer. Epidemiology 2001 Nov;12(6):604-12.
  65. Friedenreich CM, Courneya KS, Bryant HE. Relation between intensity of physical activity and breast cancer risk reduction. Med.Sci.Sports Exerc. 2001 Sep;33(9):1538-45.
  66. Magnusson CM, Roddam AW, Pike MC, Chilvers C, Crossley B, Hermon C, McPherson K, Peto J, Vessey M, Beral V. Body fatness and physical activity at young ages and the risk of breast cancer in premenopausal women. Br.J.Cancer 2005 Oct 3;93(7):817-24.
  67. Adams SA, Matthews CE, Hebert JR, Moore CG, Cunningham JE, Shu XO, Fulton J, Gao Y, Zheng W. Association of physical activity with hormone receptor status: the Shanghai Breast Cancer Study. Cancer Epidemiol.Biomarkers Prev. 2006 Jun;15(6):1170-8.
  68. Mittendorf R, Longnecker MP, Newcomb PA, Dietz AT, Greenberg ER, Bogdan GF, Clapp RW, Willett WC. Strenuous physical activity in young adulthood and risk of breast cancer (United States). Cancer Causes Control 1995 Jul;6(4):347-53.
  69. Sprague BL, Trentham-Dietz A, Newcomb PA, Titus-Ernstoff L, Hampton JM, Egan KM. Lifetime recreational and occupational physical activity and risk of in situ and invasive breast cancer. Cancer Epidemiol.Biomarkers Prev. 2007 Feb;16(2):236-43.
  70. Bernstein L, Patel AV, Ursin G, Sullivan-Halley J, Press MF, Deapen D, Berlin JA, Daling JR, McDonald JA, Norman SA, et al. Lifetime recreational exercise activity and breast cancer risk among black women and white women. J.Natl.Cancer Inst. 2005 Nov 16;97(22):1671-9.
  71. Slattery ML, Edwards S, Murtaugh MA, Sweeney C, Herrick J, Byers T, Giuliano AR, Baumgartner KB. Physical activity and breast cancer risk among women in the southwestern United States. Ann.Epidemiol. 2007 May;17(5):342-53.
  72. Lagerros YT, Hsieh SF, Hsieh CC. Physical activity in adolescence and young adulthood and breast cancer risk: a quantitative review. Eur.J.Cancer Prev. 2004 Feb;13(1):5-12.
  73. Monninkhof EM, Elias SG, Vlems FA, van dT, I, Schuit AJ, Voskuil DW, van Leeuwen FE. Physical activity and breast cancer: a systematic review. Epidemiology 2007 Jan;18(1):137-57.
  74. Carpenter CL, Ross RK, Paganini-Hill A, Bernstein L. Lifetime exercise activity and breast cancer risk among post-menopausal women. Br.J.Cancer 1999 Aug;80(11):1852-8.
  75. Enger SM, Ross RK, Paganini-Hill A, Carpenter CL, Bernstein L. Body size, physical activity, and breast cancer hormone receptor status: results from two case-control studies. Cancer Epidemiol.Biomarkers Prev. 2000 Jul;9(7):681-7.
  76. Moradi T, Adami HO, Bergstrom R, Gridley G, Wolk A, Gerhardsson M, Dosemeci M, Nyren O. Occupational physical activity and risk for breast cancer in a nationwide cohort study in Sweden. Cancer Causes Control 1999 Oct;10(5):423-30.
  77. Coogan PF, Aschengrau A. Occupational physical activity and breast cancer risk in the upper Cape Cod cancer incidence study. Am.J.Ind.Med. 1999 Aug;36(2):279-85.
  78. Polednak AP. College athletics, body size, and cancer mortality. Cancer 1976 Jul;38(1):382-7.
  79. Whittemore AS, Paffenbarger RS, Jr., Anderson K, Lee JE. Early precursors of site-specific cancers in college men and women. J.Natl.Cancer Inst. 1985 Jan;74(1):43-51.
  80. Paffenbarger RS, Jr., Hyde RT, Wing AL. Physical activity and incidence of cancer in diverse populations: a preliminary report. Am.J.Clin.Nutr. 1987 Jan;45(1 Suppl):312-7.
  81. Vena JE, Graham S, Zielezny M, Brasure J, Swanson MK. Occupational exercise and risk of cancer. Am.J.Clin.Nutr. 1987 Jan;45(1 Suppl):318-27.
  82. Severson RK, Nomura AM, Grove JS, Stemmermann GN. A prospective analysis of physical activity and cancer. Am.J.Epidemiol. 1989 Sep;130(3):522-9.
  83. Albanes D, Blair A, Taylor PR. Physical activity and risk of cancer in the NHANES I population. Am.J.Public Health 1989 Jun;79(6):744-50.
  84. Lee IM, Paffenbarger RS, Jr., Hsieh CC. Physical activity and risk of prostatic cancer among college alumni. Am.J.Epidemiol. 1992 Jan 15;135(2):169-79.
  85. Paffenbarger RS, Lee IM, Wong AL. The influence of phsyical activity on the incidence of site-specific cancers in college alumni. In: Jacobs MM, editor. Exercise, calories, fat, and cancer. New York: Plenum Press; 1992. p. 7-15.
  86. Lee IM, Paffenbarger RS, Jr. Physical activity and its relation to cancer risk: a prospective study of college alumni. Med.Sci.Sports Exerc. 1994 Jul;26(7):831-7.
  87. Thune I, Lund E. Physical activity and the risk of prostate and testicular cancer: a cohort study of 53,000 Norwegian men. Cancer Causes Control 1994 Nov;5(6):549-56.
  88. Hsing AW, McLaughlin JK, Zheng W, Gao YT, Blot WJ. Occupation, physical activity, and risk of prostate cancer in Shanghai, People's Republic of China. Cancer Causes Control 1994 Mar;5(2):136-40.
  89. Steenland K, Nowlin S, Palu S. Cancer incidence in the National Health and Nutrition Survey I. Follow-up data: diabetes, cholesterol, pulse and physical activity. Cancer Epidemiol.Biomarkers Prev. 1995 Dec;4(8):807-11.
  90. Ilic M, Vlajinac H, Marinkovic J. Case-control study of risk factors for prostate cancer. Br.J.Cancer 1996 Nov;74(10):1682-6.
  91. Oliveria SA, Kohl HW, III, Trichopoulos D, Blair SN. The association between cardiorespiratory fitness and prostate cancer. Med.Sci.Sports Exerc. 1996 Jan;28(1):97-104.
  92. Cerhan JR, Torner JC, Lynch CF, Rubenstein LM, Lemke JH, Cohen MB, Lubaroff DM, Wallace RB. Association of smoking, body mass, and physical activity with risk of prostate cancer in the Iowa 65+ Rural Health Study (United States). Cancer Causes Control 1997 Mar;8(2):229-38.
  93. Hartman TJ, Albanes D, Rautalahti M, Tangrea JA, Virtamo J, Stolzenberg R, Taylor PR. Physical activity and prostate cancer in the Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study (Finland). Cancer Causes Control 1998 Jan;9(1):11-8.
  94. Giovannucci EL, Liu Y, Leitzmann MF, Stampfer MJ, Willett WC. A prospective study of physical activity and incident and fatal prostate cancer. Arch.Intern.Med. 2005 May 9;165(9):1005-10.
  95. Liu S, Lee IM, Linson P, Ajani U, Buring JE, Hennekens CH. A prospective study of physical activity and risk of prostate cancer in US physicians. Int.J.Epidemiol. 2000 Feb;29(1):29-35.
  96. Lund Nilsen TI, Johnsen R, Vatten LJ. Socio-economic and lifestyle factors associated with the risk of prostate cancer. Br.J.Cancer 2000 Apr;82(7):1358-63.
  97. Clarke G, Whittemore AS. Prostate cancer risk in relation to anthropometry and physical activity: the National Health and Nutrition Examination Survey I Epidemiological Follow-Up Study. Cancer Epidemiol.Biomarkers Prev. 2000 Sep;9(9):875-81.
  98. Putnam SD, Cerhan JR, Parker AS, Bianchi GD, Wallace RB, Cantor KP, Lynch CF. Lifestyle and anthropometric risk factors for prostate cancer in a cohort of Iowa men. Ann.Epidemiol. 2000 Aug;10(6):361-9.
  99. Pukkala E, Kaprio J, Koskenvuo M, Kujala U, Sarna S. Cancer incidence among Finnish world class male athletes. Int.J.Sports Med. 2000 Apr;21(3):216-20.
  100. Lee IM, Sesso HD, Paffenbarger RS, Jr. A prospective cohort study of physical activity and body size in relation to prostate cancer risk (United States). Cancer Causes Control 2001 Feb;12(2):187-93.
  101. Wannamethee SG, Shaper AG, Walker M. Physical activity and risk of cancer in middle-aged men. Br.J.Cancer 2001 Nov 2;85(9):1311-6.
  102. Norman A, Moradi T, Gridley G, Dosemeci M, Rydh B, Nyren O, Wolk A. Occupational physical activity and risk for prostate cancer in a nationwide cohort study in Sweden. Br.J.Cancer 2002 Jan 7;86(1):70-5.
  103. Platz EA, Leitzmann MF, Michaud DS, Willett WC, Giovannucci E. Interrelation of energy intake, body size, and physical activity with prostate cancer in a large prospective cohort study. Cancer Res. 2003 Dec 1;63(23):8542-8.
  104. Yu H, Harris RE, Wynder EL. Case-control study of prostate cancer and socioeconomic factors. Prostate 1988;13(4):317-25.
  105. Brownson RC, Chang JC, Davis JR, Smith CA. Physical activity on the job and cancer in Missouri. Am.J.Public Health 1991 May;81(5):639-42.
  106. Le Marchand L, Kolonel LN, Yoshizawa CN. Lifetime occupational physical activity and prostate cancer risk. Am.J.Epidemiol. 1991 Jan 15;133(2):103-11.
  107. West DW, Slattery ML, Robison LM, French TK, Mahoney AW. Adult dietary intake and prostate cancer risk in Utah: a case-control study with special emphasis on aggressive tumors. Cancer Causes Control 1991 Mar;2(2):85-94.
  108. Dosemeci M, Hayes RB, Vetter R, Hoover RN, Tucker M, Engin K, Unsal M, Blair A. Occupational physical activity, socioeconomic status, and risks of 15 cancer sites in Turkey. Cancer Causes Control 1993 Jul;4(4):313-21.
  109. Andersson SO, Baron J, Wolk A, Lindgren C, Bergstrom R, Adami HO. Early life risk factors for prostate cancer: a population-based case-control study in Sweden. Cancer Epidemiol.Biomarkers Prev. 1995 Apr;4(3):187-92.
  110. Whittemore AS, Kolonel LN, Wu AH, John EM, Gallagher RP, Howe GR, Burch JD, Hankin J, Dreon DM, West DW, et al. Prostate cancer in relation to diet, physical activity, and body size in blacks, whites, and Asians in the United States and Canada. J.Natl.Cancer Inst. 1995 May 3;87(9):652-61.
  111. Sung JF, Lin RS, Pu YS, Chen YC, Chang HC, Lai MK. Risk factors for prostate carcinoma in Taiwan: a case-control study in a Chinese population. Cancer 1999 Aug 1;86(3):484-91.
  112. Villeneuve PJ, Johnson KC, Kreiger N, Mao Y. Risk factors for prostate cancer: results from the Canadian National Enhanced Cancer Surveillance System. The Canadian Cancer Registries Epidemiology Research Group. Cancer Causes Control 1999 Oct;10(5):355-67.
  113. Bairati I, Larouche R, Meyer F, Moore L, Fradet Y. Lifetime occupational physical activity and incidental prostate cancer (Canada). Cancer Causes Control 2000 Sep;11(8):759-64.
  114. Lacey JV, Jr., Deng J, Dosemeci M, Gao YT, Mostofi FK, Sesterhenn IA, Xie T, Hsing AW. Prostate cancer, benign prostatic hyperplasia and physical activity in Shanghai, China. Int.J.Epidemiol. 2001 Apr;30(2):341-9.
  115. Friedenreich CM, McGregor SE, Courneya KS, Angyalfi SJ, Elliott FG. Case-control study of lifetime total physical activity and prostate cancer risk. Am.J.Epidemiol. 2004 Apr 15;159(8):740-9.
  116. Pierotti B, Altieri A, Talamini R, Montella M, Tavani A, Negri E, Franceschi S, La VC. Lifetime physical activity and prostate cancer risk. Int.J.Cancer 2005 Apr 20;114(4):639-42.
  117. Patel AV, Rodriguez C, Jacobs EJ, Solomon L, Thun MJ, Calle EE. Recreational physical activity and risk of prostate cancer in a large cohort of U.S. men. Cancer Epidemiol.Biomarkers Prev. 2005 Jan;14(1):275-9.
  118. Jian L, Shen ZJ, Lee AH, Binns CW. Moderate physical activity and prostate cancer risk: a case-control study in China. Eur.J.Epidemiol. 2005;20(2):155-60.
  119. Zeegers MP, Dirx MJ, van den Brandt PA. Physical activity and the risk of prostate cancer in the Netherlands cohort study, results after 9.3 years of follow-up. Cancer Epidemiol.Biomarkers Prev. 2005 Jun;14(6):1490-5.
  120. Nilsen TI, Romundstad PR, Vatten LJ. Recreational physical activity and risk of prostate cancer: A prospective population-based study in Norway (the HUNT study). Int.J.Cancer 2006 Dec 15;119(12):2943-7.
  121. Littman AJ, Kristal AR, White E. Recreational physical activity and prostate cancer risk (United States). Cancer Causes Control 2006 Aug;17(6):831-41.
  122. Giovannucci E, Liu Y, Platz EA, Stampfer MJ, Willett WC. Risk factors for prostate cancer incidence and progression in the health professionals follow-up study. Int.J.Cancer 2007 Oct 1;121(7):1571-8.
  123. Darlington GA, Kreiger N, Lightfoot N, Purdham J, Sass-Kortsak A. Prostate cancer risk and diet, recreational physical activity and cigarette smoking. Chronic.Dis.Can. 2007;27(4):145-53.
  124. Giovannucci E, Ascherio A, Rimm EB, Colditz GA, Stampfer MJ, Willett WC. Physical activity, obesity, and risk for colon cancer and adenoma in men. Ann.Intern.Med. 1995 Mar 1;122(5):327-34.
  125. Calton BA, Lacey JV, Jr., Schatzkin A, Schairer C, Colbert LH, Albanes D, Leitzmann MF. Physical activity and the risk of colon cancer among women: a prospective cohort study (United States). Int.J.Cancer 2006 Jul 15;119(2):385-91.
  126. Chao A, Connell CJ, Jacobs EJ, McCullough ML, Patel AV, Calle EE, Cokkinides VE, Thun MJ. Amount, type, and timing of recreational physical activity in relation to colon and rectal cancer in older adults: the Cancer Prevention Study II Nutrition Cohort. Cancer Epidemiol.Biomarkers Prev. 2004 Dec;13(12):2187-95.
  127. Colbert LH, Hartman TJ, Malila N, Limburg PJ, Pietinen P, Virtamo J, Taylor PR, Albanes D. Physical activity in relation to cancer of the colon and rectum in a cohort of male smokers. Cancer Epidemiol.Biomarkers Prev. 2001 Mar;10(3):265-8.
  128. Larsson SC, Rutegard J, Bergkvist L, Wolk A. Physical activity, obesity, and risk of colon and rectal cancer in a cohort of Swedish men. Eur.J.Cancer 2006 Oct;42(15):2590-7.
  129. Lee IM, Manson JE, Ajani U, Paffenbarger RS, Jr., Hennekens CH, Buring JE. Physical activity and risk of colon cancer: the Physicians' Health Study (United States). Cancer Causes Control 1997 Jul;8(4):568-74.
  130. Lee KJ, Inoue M, Otani T, Iwasaki M, Sasazuki S, Tsugane S. Physical activity and risk of colorectal cancer in Japanese men and women: the Japan Public Health Center-based prospective study. Cancer Causes Control 2007 Mar;18(2):199-209.
  131. Mai PL, Sullivan-Halley J, Ursin G, Stram DO, Deapen D, Villaluna D, Horn-Ross PL, Clarke CA, Reynolds P, Ross RK, et al. Physical activity and colon cancer risk among women in the California Teachers Study. Cancer Epidemiol.Biomarkers Prev. 2007 Mar;16(3):517-25.
  132. Martinez ME, Giovannucci E, Spiegelman D, Hunter DJ, Willett WC, Colditz GA. Leisure-time physical activity, body size, and colon cancer in women. Nurses' Health Study Research Group. J.Natl.Cancer Inst. 1997 Jul 2;89(13):948-55.
  133. Thune I, Lund E. Physical activity and risk of colorectal cancer in men and women. Br.J.Cancer 1996 May;73(9):1134-40.
  134. Hou L, Ji BT, Blair A, Dai Q, Gao YT, Chow WH. Commuting physical activity and risk of colon cancer in Shanghai, China. Am.J.Epidemiol. 2004 Nov 1;160(9):860-7.
  135. Isomura K, Kono S, Moore MA, Toyomura K, Nagano J, Mizoue T, Mibu R, Tanaka M, Kakeji Y, Maehara Y, et al. Physical activity and colorectal cancer: the Fukuoka Colorectal Cancer Study. Cancer Sci. 2006 Oct;97(10):1099-104.
  136. Levi F, Pasche C, Lucchini F, Tavani A, La VC. Occupational and leisure-time physical activity and the risk of colorectal cancer. Eur.J.Cancer Prev. 1999 Dec;8(6):487-93.
  137. Slattery ML, Edwards SL, Ma KN, Friedman GD, Potter JD. Physical activity and colon cancer: a public health perspective. Ann.Epidemiol. 1997 Feb;7(2):137-45.
  138. Slattery ML, Potter J, Caan B, Edwards S, Coates A, Ma KN, Berry TD. Energy balance and colon cancer--beyond physical activity. Cancer Res. 1997 Jan 1;57(1):75-80.
  139. Slattery ML, Potter JD. Physical activity and colon cancer: confounding or interaction? Med.Sci.Sports Exerc. 2002 Jun;34(6):913-9.
  140. Slattery ML, Edwards S, Curtin K, Ma K, Edwards R, Holubkov R, Schaffer D. Physical activity and colorectal cancer. Am.J.Epidemiol. 2003 Aug 1;158(3):214-24.
  141. White E, Jacobs EJ, Daling JR. Physical activity in relation to colon cancer in middle-aged men and women. Am.J.Epidemiol. 1996 Jul 1;144(1):42-50.
  142. Zhang Y, Cantor KP, Dosemeci M, Lynch CF, Zhu Y, Zheng T. Occupational and leisure-time physical activity and risk of colon cancer by subsite. J.Occup.Environ.Med. 2006 Mar;48(3):236-43.
  143. Tavani A, Braga C, La VC, Conti E, Filiberti R, Montella M, Amadori D, Russo A, Franceschi S. Physical activity and risk of cancers of the colon and rectum: an Italian case-control study. Br.J.Cancer 1999 Apr;79(11-12):1912-6.
  144. Tang R, Wang JY, Lo SK, Hsieh LL. Physical activity, water intake and risk of colorectal cancer in Taiwan: a hospital-based case-control study. Int.J.Cancer 1999 Aug 12;82(4):484-9.
  145. Lee IM, Oguma Y. Physical activity. In: Schottenfeld D, Fraumeni JF, editors. Cancer epidemiology and prevention. 3rd ed. New York: Oxford University Press; 2006. p. 449-67.
  146. Mao Y, Pan S, Wen SW, Johnson KC. Physical inactivity, energy intake, obesity and the risk of rectal cancer in Canada. Int.J.Cancer 2003 Jul 20;105(6):831-7.
  147. Steindorf K, Friedenreich C, Linseisen J, Rohrmann S, Rundle A, Veglia F, Vineis P, Johnsen NF, Tjonneland A, Overvad K, et al. Physical activity and lung cancer risk in the European Prospective Investigation into Cancer and Nutrition Cohort. Int.J.Cancer 2006 Nov 15;119(10):2389-97.
  148. Sinner P, Folsom AR, Harnack L, Eberly LE, Schmitz KH. The association of physical activity with lung cancer incidence in a cohort of older women: the Iowa Women's Health Study. Cancer Epidemiol.Biomarkers Prev. 2006 Dec;15(12):2359-63.
  149. Thune I, Lund E. The influence of physical activity on lung-cancer risk: A prospective study of 81,516 men and women. Int.J.Cancer 1997 Jan 6;70(1):57-62.
  150. Lee IM, Sesso HD, Paffenbarger RS, Jr. Physical activity and risk of lung cancer. Int.J.Epidemiol. 1999 Aug;28(4):620-5.
  151. Colbert LH, Hartman TJ, Tangrea JA, Pietinen P, Virtamo J, Taylor PR, Albanes D. Physical activity and lung cancer risk in male smokers. Int.J.Cancer 2002 Apr 10;98(5):770-3.
  152. Bak H, Christensen J, Thomsen BL, Tjonneland A, Overvad K, Loft S, Raaschou-Nielsen O. Physical activity and risk for lung cancer in a Danish cohort. Int.J.Cancer 2005 Sep 1;116(3):439-44.
  153. Alfano CM, Klesges RC, Murray DM, Bowen DJ, McTiernan A, Vander Weg MW, Robinson LA, Cartmel B, Thornquist MD, Barnett M, et al. Physical activity in relation to all-site and lung cancer incidence and mortality in current and former smokers. Cancer Epidemiol.Biomarkers Prev. 2004 Dec;13(12):2233-41.
  154. Kubik A, Zatloukal P, Tomasek L, Pauk N, Petruzelka L, Plesko I. Lung cancer risk among nonsmoking women in relation to diet and physical activity. Neoplasma 2004;51(2):136-43.
  155. Kubik AK, Zatloukal P, Tomasek L, Pauk N, Havel L, Krepela E, Petruzelka L. Dietary habits and lung cancer risk among non-smoking women. Eur.J.Cancer Prev. 2004 Dec;13(6):471-80.
  156. Mao Y, Pan S, Wen SW, Johnson KC. Physical activity and the risk of lung cancer in Canada. Am.J.Epidemiol. 2003 Sep 15;158(6):564-75.
  157. Moradi T, Nyren O, Bergstrom R, Gridley G, Linet M, Wolk A, Dosemeci M, Adami HO. Risk for endometrial cancer in relation to occupational physical activity: a nationwide cohort study in Sweden. Int.J.Cancer 1998 May 29;76(5):665-70.
  158. Terry P, Baron JA, Weiderpass E, Yuen J, Lichtenstein P, Nyren O. Lifestyle and endometrial cancer risk: a cohort study from the Swedish Twin Registry. Int.J.Cancer 1999 Jul 2;82(1):38-42.
  159. Colbert LH, Lacey JV, Jr., Schairer C, Albert P, Schatzkin A, Albanes D. Physical activity and risk of endometrial cancer in a prospective cohort study (United States). Cancer Causes Control 2003 Aug;14(6):559-67.
  160. Friberg E, Mantzoros CS, Wolk A. Physical activity and risk of endometrial cancer: a population-based prospective cohort study. Cancer Epidemiol.Biomarkers Prev. 2006 Nov;15(11):2136-40.
  161. Friedenreich C, Cust A, Lahmann PH, Steindorf K, Boutron-Ruault MC, Clavel-Chapelon F, Mesrine S, Linseisen J, Rohrmann S, Pischon T, et al. Physical activity and risk of endometrial cancer: the European prospective investigation into cancer and nutrition. Int.J.Cancer 2007 Jul 15;121(2):347-55.
  162. Furberg AS, Thune I. Metabolic abnormalities (hypertension, hyperglycemia and overweight), lifestyle (high energy intake and physical inactivity) and endometrial cancer risk in a Norwegian cohort. Int.J.Cancer 2003 May 10;104(6):669-76.
  163. Schouten LJ, Goldbohm RA, van den Brandt PA. Anthropometry, physical activity, and endometrial cancer risk: results from the Netherlands Cohort Study. J.Natl.Cancer Inst. 2004 Nov 3;96(21):1635-8.
  164. Hirose K, Tajima K, Hamajima N, Takezaki T, Inoue M, Kuroishi T, Kuzuya K, Nakamura S, Tokudome S. Subsite (cervix/endometrium)-specific risk and protective factors in uterus cancer. Jpn.J.Cancer Res. 1996 Sep;87(9):1001-9.
  165. Kalandidi A, Tzonou A, Lipworth L, Gamatsi I, Filippa D, Trichopoulos D. A case-control study of endometrial cancer in relation to reproductive, somatometric, and life-style variables. Oncology 1996 Sep;53(5):354-9.
  166. Goodman MT, Hankin JH, Wilkens LR, Lyu LC, McDuffie K, Liu LQ, Kolonel LN. Diet, body size, physical activity, and the risk of endometrial cancer. Cancer Res. 1997 Nov 15;57(22):5077-85.
  167. Olson SH, Vena JE, Dorn JP, Marshall JR, Zielezny M, Laughlin R, Graham S. Exercise, occupational activity, and risk of endometrial cancer. Ann.Epidemiol. 1997 Jan;7(1):46-53.
  168. Moradi T, Weiderpass E, Signorello LB, Persson I, Nyren O, Adami HO. Physical activity and postmenopausal endometrial cancer risk (Sweden). Cancer Causes Control 2000 Oct;11(9):829-37.
  169. Salazar-Martinez E, Lazcano-Ponce EC, Lira-Lira GG, Escudero-De los RP, Salmeron-Castro J, Larrea F, Hernandez-Avila M. Case-control study of diabetes, obesity, physical activity and risk of endometrial cancer among Mexican women. Cancer Causes Control 2000 Sep;11(8):707-11.
  170. Littman AJ, Voigt LF, Beresford SA, Weiss NS. Recreational physical activity and endometrial cancer risk. Am.J.Epidemiol. 2001 Nov 15;154(10):924-33.
  171. Matthews CE, Xu WH, Zheng W, Gao YT, Ruan ZX, Cheng JR, Xiang YB, Shu XO. Physical activity and risk of endometrial cancer: a report from the Shanghai endometrial cancer study. Cancer Epidemiol.Biomarkers Prev. 2005 Apr;14(4):779-85.
  172. Olsen CM, Green AC, Whiteman DC, Sadeghi S, Kolahdooz F, Webb PM. Obesity and the risk of epithelial ovarian cancer: a systematic review and meta-analysis. Eur.J.Cancer 2007 Mar;43(4):690-709.
  173. Sinner PJ, Schmitz KH, Anderson KE, Folsom AR. Lack of association of physical activity and obesity with incident pancreatic cancer in elderly women. Cancer Epidemiol.Biomarkers Prev. 2005 Jun;14(6):1571-3.
  174. Lee IM, Sesso HD, Oguma Y, Paffenbarger RS, Jr. Physical activity, body weight, and pancreatic cancer mortality. Br.J.Cancer 2003 Mar 10;88(5):679-83.
  175. Michaud DS, Giovannucci E, Willett WC, Colditz GA, Stampfer MJ, Fuchs CS. Physical activity, obesity, height, and the risk of pancreatic cancer. JAMA 2001 Aug 22;286(8):921-9.
  176. Patel AV, Rodriguez C, Bernstein L, Chao A, Thun MJ, Calle EE. Obesity, recreational physical activity, and risk of pancreatic cancer in a large U.S. Cohort. Cancer Epidemiol.Biomarkers Prev. 2005 Feb;14(2):459-66.
  177. Berrington de Gonzalez A, Spencer EA, Bueno-de-Mesquita HB, Roddam A, Stolzenberg-Solomon R, Halkjaer J, Tjonneland A, Overvad K, Clavel-Chapelon F, Boutron-Ruault MC, et al. Anthropometry, physical activity, and the risk of pancreatic cancer in the European prospective investigation into cancer and nutrition. Cancer Epidemiol.Biomarkers Prev. 2006 May;15(5):879-85.
  178. Luo J, Iwasaki M, Inoue M, Sasazuki S, Otani T, Ye W, Tsugane S. Body mass index, physical activity and the risk of pancreatic cancer in relation to smoking status and history of diabetes: a large-scale population-based cohort study in Japan--the JPHC study. Cancer Causes Control 2007 Aug;18(6):603-12.
  179. Lin Y, Kikuchi S, Tamakoshi A, Yagyu K, Obata Y, Inaba Y, Kurosawa M, Kawamura T, Motohashi Y, Ishibashi T. Obesity, physical activity and the risk of pancreatic cancer in a large Japanese cohort. Int.J.Cancer 2007 Jun 15;120(12):2665-71.
  180. Nothlings U, Wilkens LR, Murphy SP, Hankin JH, Henderson BE, Kolonel LN. Body mass index and physical activity as risk factors for pancreatic cancer: the Multiethnic Cohort Study. Cancer Causes Control 2007 Mar;18(2):165-75.
  181. Hanley AJ, Johnson KC, Villeneuve PJ, Mao Y. Physical activity, anthropometric factors and risk of pancreatic cancer: results from the Canadian enhanced cancer surveillance system. Int.J.Cancer 2001 Oct 1;94(1):140-7.
  182. Eberle CA, Bracci PM, Holly EA. Anthropometric factors and pancreatic cancer in a population-based case-control study in the San Francisco Bay area. Cancer Causes Control 2005 Dec;16(10):1235-44.
  183. Giovannucci E, Michaud D. The role of obesity and related metabolic disturbances in cancers of the colon, prostate, and pancreas. Gastroenterology 2007 May;132(6):2208-25.
  184. Hewitt ME, Greenfield S, Stovall E, National Cancer Policy Board (U.S.). From cancer patient to cancer survivor : lost in transition. Washington, D.C.: National Academies Press; 2006.
  185. Aziz NM, Rowland JH. Trends and advances in cancer survivorship research: challenge and opportunity. Semin.Radiat.Oncol. 2003 Jul;13(3):248-66.
  186. Carver JR, Shapiro CL, Ng A, Jacobs L, Schwartz C, Virgo KS, Hagerty KL, Somerfield MR, Vaughn DJ. American Society of Clinical Oncology clinical evidence review on the ongoing care of adult cancer survivors: cardiac and pulmonary late effects. J.Clin.Oncol. 2007 Sep 1;25(25):3991-4008.
  187. Schmitz KH, Cappola AR, Stricker CT, Sweeney C, Norman SA. The intersection of cancer and aging: establishing the need for breast cancer rehabilitation. Cancer Epidemiol.Biomarkers Prev. 2007 May;16(5):866-72.
  188. Schmitz KH, Holtzman J, Courneya KS, Masse LC, Duval S, Kane R. Controlled physical activity trials in cancer survivors: a systematic review and meta-analysis. Cancer Epidemiol.Biomarkers Prev. 2005 Jul;14(7):1588-95.
  189. Markes M, Brockow T, Resch KL. Exercise for women receiving adjuvant therapy for breast cancer. Cochrane.Database.Syst.Rev. 2006;(4):CD005001.
  190. Holmes MD, Chen WY, Feskanich D, Kroenke CH, Colditz GA. Physical activity and survival after breast cancer diagnosis. JAMA 2005 May 25;293(20):2479-86.
  191. Chlebowski RT, Aiello E, McTiernan A. Weight loss in breast cancer patient management. J.Clin.Oncol. 2002 Feb 15;20(4):1128-43.
  192. Kroenke CH, Rosner B, Chen WY, Kawachi I, Colditz GA, Holmes MD. Functional impact of breast cancer by age at diagnosis. J.Clin.Oncol. 2004 May 15;22(10):1849-56.
  193. Trentham-Dietz A, Newcomb PA, Nichols HB, Hampton JM. Breast cancer risk factors and second primary malignancies among women with breast cancer. Breast Cancer Res.Treat. 2007 Oct;105(2):195-207.
  194. Meyerhardt JA, Giovannucci EL, Holmes MD, Chan AT, Chan JA, Colditz GA, Fuchs CS. Physical activity and survival after colorectal cancer diagnosis. J.Clin.Oncol. 2006 Aug 1;24(22):3527-34.
  195. Meyerhardt JA, Heseltine D, Niedzwiecki D, Hollis D, Saltz LB, Mayer RJ, Thomas J, Nelson H, Whittom R, Hantel A, et al. Impact of physical activity on cancer recurrence and survival in patients with stage III colon cancer: findings from CALGB 89803. J.Clin.Oncol. 2006 Aug 1;24(22):3535-41.
  196. Bicego D, Brown K, Ruddick M, Storey D, Wong C, Harris SR. Exercise for women with or at risk for breast cancer-related lymphedema. Phys.Ther. 2006 Oct;86(10):1398-405.
  197. Ingram C, Courneya KS, Kingston D. The effects of exercise on body weight and composition in breast cancer survivors: an integrative systematic review. Oncol.Nurs.Forum 2006 Sep;33(5):937-47.
  198. Hewitt JA, Mokbel K, van Someren KA, Jewell AP, Garrod R. Exercise for breast cancer survival: the effect on cancer risk and cancer-related fatigue (CRF). Int.J.Fertil.Womens Med. 2005 Sep;50(5 Pt 1):231-9.
  199. Knols R, Aaronson NK, Uebelhart D, Fransen J, Aufdemkampe G. Physical exercise in cancer patients during and after medical treatment: a systematic review of randomized and controlled clinical trials. J.Clin.Oncol. 2005 Jun 1;23(16):3830-42.
  200. Galvao DA, Newton RU. Review of exercise intervention studies in cancer patients. J.Clin.Oncol. 2005 Feb 1;23(4):899-909.
  201. Stevinson C, Lawlor DA, Fox KR. Exercise interventions for cancer patients: systematic review of controlled trials. Cancer Causes Control 2004 Dec;15(10):1035-56.
  202. Stricker CT, Drake D, Hoyer KA, Mock V. Evidence-based practice for fatigue management in adults with cancer: exercise as an intervention. Oncol.Nurs.Forum 2004 Sep;31(5):963-76.
  203. Courneya KS, Friedenreich CM, Quinney HA, Fields AL, Jones LW, Fairey AS. Predictors of adherence and contamination in a randomized trial of exercise in colorectal cancer survivors. Psychooncology. 2004 Dec;13(12):857-66.
  204. Oldervoll LM, Kaasa S, Hjermstad MJ, Lund JA, Loge JH. Physical exercise results in the improved subjective well-being of a few or is effective rehabilitation for all cancer patients? Eur.J.Cancer 2004 May;40(7):951-62.
  205. Irwin ML, Ainsworth BE. Physical activity interventions following cancer diagnosis: methodologic challenges to delivery and assessment. Cancer Invest 2004;22(1):30-50.
  206. Shamley DR, Barker K, Simonite V, Beardshaw A. Delayed versus immediate exercises following surgery for breast cancer: a systematic review. Breast Cancer Res.Treat. 2005 Apr;90(3):263-71.
  207. Burnham TR, Wilcox A. Effects of exercise on physiological and psychological variables in cancer survivors. Med.Sci.Sports Exerc. 2002 Dec;34(12):1863-7.
  208. Schmitz KH, Ahmed RL, Hannan PJ, Yee D. Safety and efficacy of weight training in recent breast cancer survivors to alter body composition, insulin, and insulin-like growth factor axis proteins. Cancer Epidemiol.Biomarkers Prev. 2005 Jul;14(7):1672-80.
  209. Thorsen L, Skovlund E, Stromme SB, Hornslien K, Dahl AA, Fossa SD. Effectiveness of physical activity on cardiorespiratory fitness and health-related quality of life in young and middle-aged cancer patients shortly after chemotherapy. J.Clin.Oncol. 2005 Apr 1;23(10):2378-88.
  210. Pinto BM, Frierson GM, Rabin C, Trunzo JJ, Marcus BH. Home-based physical activity intervention for breast cancer patients. J.Clin.Oncol. 2005 May 20;23(15):3577-87.
  211. Mustian KM, Katula JA, Zhao H. A pilot study to assess the influence of tai chi chuan on functional capacity among breast cancer survivors. J.Support.Oncol. 2006 Mar;4(3):139-45.
  212. Hutnick NA, Williams NI, Kraemer WJ, Orsega-Smith E, Dixon RH, Bleznak AD, Mastro AM. Exercise and lymphocyte activation following chemotherapy for breast cancer. Med.Sci.Sports Exerc. 2005 Nov;37(11):1827-35.
  213. Herrero F, San Juan AF, Fleck SJ, Balmer J, Perez M, Canete S, Earnest CP, Foster C, Lucia A. Combined aerobic and resistance training in breast cancer survivors: A randomized, controlled pilot trial. Int.J.Sports Med. 2006 Jul;27(7):573-80.
  214. Daley AJ, Crank H, Saxton JM, Mutrie N, Coleman R, Roalfe A. Randomized trial of exercise therapy in women treated for breast cancer. J.Clin.Oncol. 2007 May 1;25(13):1713-21.
  215. Culos-Reed SN, Carlson LE, Daroux LM, Hately-Aldous S. A pilot study of yoga for breast cancer survivors: physical and psychological benefits. Psychooncology. 2006 Oct;15(10):891-7.
  216. Bennett JA, Lyons KS, Winters-Stone K, Nail LM, Scherer J. Motivational interviewing to increase physical activity in long-term cancer survivors: a randomized controlled trial. Nurs.Res. 2007 Jan;56(1):18-27.
  217. Basen-Engquist K, Taylor CL, Rosenblum C, Smith MA, Shinn EH, Greisinger A, Gregg X, Massey P, Valero V, Rivera E. Randomized pilot test of a lifestyle physical activity intervention for breast cancer survivors. Patient.Educ.Couns. 2006 Dec;64(1-3):225-34.
  218. Demark-Wahnefried W, Peterson BL, Winer EP, Marks L, Aziz N, Marcom PK, Blackwell K, Rimer BK. Changes in weight, body composition, and factors influencing energy balance among premenopausal breast cancer patients receiving adjuvant chemotherapy. J.Clin.Oncol. 2001 May 1;19(9):2381-9.
  219. Irwin ML, Crumley D, McTiernan A, Bernstein L, Baumgartner R, Gilliland FD, Kriska A, Ballard-Barbash R. Physical activity levels before and after a diagnosis of breast carcinoma: the Health, Eating, Activity, and Lifestyle (HEAL) study. Cancer 2003 Apr 1;97(7):1746-57.
  220. Sprod LK, Drum SN, Bentz AT, Carter SD, Schneider CM. The effects of walking poles on shoulder function in breast cancer survivors. Integr.Cancer Ther. 2005 Dec;4(4):287-93.
  221. Ahmed RL, Thomas W, Yee D, Schmitz KH. Randomized controlled trial of weight training and lymphedema in breast cancer survivors. J.Clin.Oncol. 2006 Jun 20;24(18):2765-72.
  222. Courneya KS, Friedenreich CM, Sela RA, Quinney HA, Rhodes RE, Handman M. The group psychotherapy and home-based physical exercise (group-hope) trial in cancer survivors: physical fitness and quality of life outcomes. Psychooncology. 2003 Jun;12(4):357-74.
  223. Cho OH, Yoo YS, Kim NC. Efficacy of comprehensive group rehabilitation for women with early breast cancer in South Korea. Nurs.Health Sci. 2006 Sep;8(3):140-6.
  224. Sandel SL, Judge JO, Landry N, Faria L, Ouellette R, Majczak M. Dance and movement program improves quality-of-life measures in breast cancer survivors. Cancer Nurs. 2005 Jul;28(4):301-9.
  225. Mansel RE, Fallowfield L, Kissin M, Goyal A, Newcombe RG, Dixon JM, Yiangou C, Horgan K, Bundred N, Monypenny I, et al. Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial. J.Natl.Cancer Inst. 2006 May 3;98(9):599-609.
  226. Paskett ED, Naughton MJ, McCoy TP, Case LD, Abbott JM. The epidemiology of arm and hand swelling in premenopausal breast cancer survivors. Cancer Epidemiol.Biomarkers Prev. 2007 Apr;16(4):775-82.
  227. Petrek JA, Naughton MJ, Case LD, Paskett ED, Naftalis EZ, Singletary SE, Sukumvanich P. Incidence, time course, and determinants of menstrual bleeding after breast cancer treatment: a prospective study. J.Clin.Oncol. 2006 Mar 1;24(7):1045-51.
  228. van Akkooi AC, Bouwhuis MG, van Geel AN, Hoedemaker R, Verhoef C, Grunhagen DJ, Schmitz PI, Eggermont AM, de Wilt JH. Morbidity and prognosis after therapeutic lymph node dissections for malignant melanoma. Eur.J.Surg.Oncol. 2007 Feb;33(1):102-8.
  229. Wrightson WR, Wong SL, Edwards MJ, Chao C, Reintgen DS, Ross MI, Noyes RD, Viar V, Cerrito PB, McMasters KM. Complications associated with sentinel lymph node biopsy for melanoma. Ann.Surg.Oncol. 2003 Jul;10(6):676-80.
  230. Karakousis CP, Driscoll DL, Rose B, Walsh DL. Groin dissection in malignant melanoma. Ann.Surg.Oncol. 1994 Jul;1(4):271-7.
  231. Okeke AA, Bates DO, Gillatt DA. Lymphoedema in urological cancer. Eur.Urol. 2004 Jan;45(1):18-25.
  232. Werngren-Elgstrom M, Lidman D. Lymphoedema of the lower extremities after surgery and radiotherapy for cancer of the cervix. Scand.J.Plast.Reconstr.Surg.Hand Surg. 1994 Dec;28(4):289-93.
  233. Haberthur F, Almendral AC, Ritter B. Therapy of vulvar carcinoma. Eur.J.Gynaecol.Oncol. 1993;14(3):218-27.
  234. Karakousis CP, Heiser MA, Moore RH. Lymphedema after groin dissection. Am.J.Surg. 1983 Feb;145(2):205-8.
  235. Ingvar C, Erichsen C, Jonsson PE. Morbidity following prophylactic and therapeutic lymph node dissection for melanoma--a comparison. Tumori 1984 Dec 31;70(6):529-33.
  236. Urist MM, Maddox WA, Kennedy JE, Balch CM. Patient risk factors and surgical morbidity after regional lymphadenectomy in 204 melanoma patients. Cancer 1983 Jun 1;51(11):2152-6.
  237. de Vries M, Vonkeman WG, van Ginkel RJ, Hoekstra HJ. Morbidity after inguinal sentinel lymph node biopsy and completion lymph node dissection in patients with cutaneous melanoma. Eur.J.Surg.Oncol. 2006 Sep;32(7):785-9.
  238. McKenzie DC, Kalda AL. Effect of upper extremity exercise on secondary lymphedema in breast cancer patients: a pilot study. J.Clin.Oncol. 2003 Feb 1;21(3):463-6.
  239. Courneya KS, Mackey JR, Bell GJ, Jones LW, Field CJ, Fairey AS. Randomized controlled trial of exercise training in postmenopausal breast cancer survivors: cardiopulmonary and quality of life outcomes. J.Clin.Oncol. 2003 May 1;21(9):1660-8.
  240. Demark-Wahnefried W, Clipp EC, Morey MC, Pieper CF, Sloane R, Snyder DC, Cohen HJ. Lifestyle intervention development study to improve physical function in older adults with cancer: outcomes from Project LEAD. J.Clin.Oncol. 2006 Jul 20;24(21):3465-73.
  241. Matthews CE, Wilcox S, Hanby CL, Der AC, Heiney SP, Gebretsadik T, Shintani A. Evaluation of a 12-week home-based walking intervention for breast cancer survivors. Support.Care Cancer 2007 Feb;15(2):203-11.
  242. Ohira T, Schmitz KH, Ahmed RL, Yee D. Effects of weight training on quality of life in recent breast cancer survivors: the Weight Training for Breast Cancer Survivors (WTBS) study. Cancer 2006 May 1;106(9):2076-83.
  243. Ryan JL, Carroll JK, Ryan EP, Mustian KM, Fiscella K, Morrow GR. Mechanisms of cancer-related fatigue. Oncologist. 2007;12 Suppl 1:22-34.
  244. Pinto BM, Clark MM, Maruyama NC, Feder SI. Psychological and fitness changes associated with exercise participation among women with breast cancer. Psychooncology. 2003 Mar;12(2):118-26.
  245. McTiernan A. Mechanisms linking physical activity with cancer. Nat.Rev.Cancer 2008 Jan 31.
  246. Bernstein L. Epidemiology of endocrine-related risk factors for breast cancer. J.Mammary.Gland.Biol.Neoplasia. 2002 Jan;7(1):3-15.
  247. Roddam AW, Allen NE, Appleby P, Key TJ. Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. J.Natl.Cancer Inst. 2008 Feb 6;100(3):170-83.
  248. Eliassen AH, Missmer SA, Tworoger SS, Spiegelman D, Barbieri RL, Dowsett M, Hankinson SE. Endogenous steroid hormone concentrations and risk of breast cancer among premenopausal women. J.Natl.Cancer Inst. 2006 Oct 4;98(19):1406-15.
  249. Kaaks R, Berrino F, Key T, Rinaldi S, Dossus L, Biessy C, Secreto G, Amiano P, Bingham S, Boeing H, et al. Serum sex steroids in premenopausal women and breast cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC). J.Natl.Cancer Inst. 2005 May 18;97(10):755-65.
  250. Winer EP, Hudis C, Burstein HJ, Wolff AC, Pritchard KI, Ingle JN, Chlebowski RT, Gelber R, Edge SB, Gralow J, et al. American Society of Clinical Oncology technology assessment on the use of aromatase inhibitors as adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer: status report 2004. J.Clin.Oncol. 2005 Jan 20;23(3):619-29.
  251. Lukanova A, Lundin E, Micheli A, Arslan A, Ferrari P, Rinaldi S, Krogh V, Lenner P, Shore RE, Biessy C, et al. Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women. Int.J.Cancer 2004 Jan 20;108(3):425-32.
  252. Tammela T. Endocrine treatment of prostate cancer. J.Steroid Biochem.Mol.Biol. 2004 Nov;92(4):287-95.
  253. Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, Lieber MM, Cespedes RD, Atkins JN, Lippman SM, et al. The influence of finasteride on the development of prostate cancer. N.Engl.J.Med. 2003 Jul 17;349(3):215-24.
  254. McTiernan A, Ulrich C, Slate S, Potter J. Physical activity and cancer etiology: associations and mechanisms. Cancer Causes Control 1998 Oct;9(5):487-509.
  255. Loucks AB. Energy availability, not body fatness, regulates reproductive function in women. Exerc.Sport Sci.Rev. 2003 Jul;31(3):144-8.
  256. Loucks AB, Redman LM. The effect of stress on menstrual function. Trends Endocrinol.Metab 2004 Dec;15(10):466-71.
  257. Williams NI, Helmreich DL, Parfitt DB, Caston-Balderrama A, Cameron JL. Evidence for a causal role of low energy availability in the induction of menstrual cycle disturbances during strenuous exercise training. J.Clin.Endocrinol.Metab 2001 Nov;86(11):5184-93.
  258. Bonen A. Recreational exercise does not impair menstrual cycles: a prospective study. Int.J.Sports Med. 1992 Feb;13(2):110-20.
  259. Rogol AD, Weltman A, Weltman JY, Seip RL, Snead DB, Levine S, Haskvitz EM, Thompson DL, Schurrer R, Dowling E, et al. Durability of the reproductive axis in eumenorrheic women during 1 yr of endurance training. J.Appl.Physiol 1992 Apr;72(4):1571-80.
  260. Bullen BA, Skrinar GS, Beitins IZ, Carr DB, Reppert SM, Dotson CO, Fencl MD, Gervino EV, McArthur JW. Endurance training effects on plasma hormonal responsiveness and sex hormone excretion. J.Appl.Physiol 1984 Jun;56(6):1453-63.
  261. Bullen BA, Skrinar GS, Beitins IZ, von MG, Turnbull BA, McArthur JW. Induction of menstrual disorders by strenuous exercise in untrained women. N.Engl.J.Med. 1985 May 23;312(21):1349-53.
  262. Keizer HA, Kuipers H, de HJ, Janssen GM, Beckers E, Habets L, van KG, Geurten P. Effect of a 3-month endurance training program on metabolic and multiple hormonal responses to exercise. Int.J.Sports Med. 1987 Dec;8 Suppl 3:154-60.
  263. Tworoger SS, Missmer SA, Eliassen AH, Barbieri RL, Dowsett M, Hankinson SE. Physical activity and inactivity in relation to sex hormone, prolactin, and insulin-like growth factor concentrations in premenopausal women - exercise and premenopausal hormones. Cancer Causes Control 2007 Sep;18(7):743-52.
  264. Chan MF, Dowsett M, Folkerd E, Bingham S, Wareham N, Luben R, Welch A, Khaw KT. Usual physical activity and endogenous sex hormones in postmenopausal women: the European prospective investigation into cancer-norfolk population study. Cancer Epidemiol.Biomarkers Prev. 2007 May;16(5):900-5.
  265. McTiernan A, Wu L, Chen C, Chlebowski R, Mossavar-Rahmani Y, Modugno F, Perri MG, Stanczyk FZ, Van HL, Wang CY. Relation of BMI and physical activity to sex hormones in postmenopausal women. Obesity.(Silver.Spring) 2006 Sep;14(9):1662-77.
  266. Verkasalo PK, Thomas HV, Appleby PN, Davey GK, Key TJ. Circulating levels of sex hormones and their relation to risk factors for breast cancer: a cross-sectional study in 1092 pre- and postmenopausal women (United Kingdom). Cancer Causes Control 2001 Jan;12(1):47-59.
  267. McTiernan A, Tworoger SS, Ulrich CM, Yasui Y, Irwin ML, Rajan KB, Sorensen B, Rudolph RE, Bowen D, Stanczyk FZ, et al. Effect of exercise on serum estrogens in postmenopausal women: a 12-month randomized clinical trial. Cancer Res. 2004 Apr 15;64(8):2923-8.
  268. McTiernan A, Tworoger SS, Rajan KB, Yasui Y, Sorenson B, Ulrich CM, Chubak J, Stanczyk FZ, Bowen D, Irwin ML, et al. Effect of exercise on serum androgens in postmenopausal women: a 12-month randomized clinical trial. Cancer Epidemiol.Biomarkers Prev. 2004 Jul;13(7):1099-105.
  269. De Souza MJ, Miller BE. The effect of endurance training on reproductive function in male runners. A 'volume threshold' hypothesis. Sports Med. 1997 Jun;23(6):357-74.
  270. Hawkins VN, Foster-Schubert K, Chubak J, Sorensen B, Ulrich CM, Stancyzk FZ, Plymate S, Stanford J, White E, Potter JD, et al. Effect of Exercise on Serum Sex Hormones in Men: A 12-Month Randomized Clinical Trial. Med.Sci.Sports Exerc. 2008 Feb;40(2):223-33.
  271. Kaaks R, Lukanova A. Energy balance and cancer: the role of insulin and insulin-like growth factor-I. Proc.Nutr.Soc. 2001 Feb;60(1):91-106.
  272. Wolf I, Sadetzki S, Catane R, Karasik A, Kaufman B. Diabetes mellitus and breast cancer. Lancet Oncol. 2005 Feb;6(2):103-11.
  273. Boule NG, Haddad E, Kenny GP, Wells GA, Sigal RJ. Effects of exercise on glycemic control and body mass in type 2 diabetes mellitus: a meta-analysis of controlled clinical trials. JAMA 2001 Sep 12;286(10):1218-27.
  274. Frank LL, Sorensen BE, Yasui Y, Tworoger SS, Schwartz RS, Ulrich CM, Irwin ML, Rudolph RE, Rajan KB, Stanczyk F, et al. Effects of exercise on metabolic risk variables in overweight postmenopausal women: a randomized clinical trial. Obes.Res. 2005 Mar;13(3):615-25.
  275. Ross R, Dagnone D, Jones PJ, Smith H, Paddags A, Hudson R, Janssen I. Reduction in obesity and related comorbid conditions after diet-induced weight loss or exercise-induced weight loss in men. A randomized, controlled trial. Ann.Intern.Med. 2000 Jul 18;133(2):92-103.
  276. Ross R, Janssen I, Dawson J, Kungl AM, Kuk JL, Wong SL, Nguyen-Duy TB, Lee S, Kilpatrick K, Hudson R. Exercise-induced reduction in obesity and insulin resistance in women: a randomized controlled trial. Obes.Res. 2004 May;12(5):789-98.
  277. Duncan GE, Perri MG, Theriaque DW, Hutson AD, Eckel RH, Stacpoole PW. Exercise training, without weight loss, increases insulin sensitivity and postheparin plasma lipase activity in previously sedentary adults. Diabetes Care 2003 Mar;26(3):557-62.
  278. Campbell KL, McTiernan A. Exercise and biomarkers for cancer prevention studies. J.Nutr. 2007 Jan;137(1 Suppl):161S-9S.
  279. Tworoger SS, Eliassen AH, Sluss P, Hankinson SE. A prospective study of plasma prolactin concentrations and risk of premenopausal and postmenopausal breast cancer. J.Clin.Oncol. 2007 Apr 20;25(12):1482-8.
  280. Tworoger SS, Sorensen B, Chubak J, Irwin M, Stanczyk FZ, Ulrich CM, Potter J, McTiernan A. Effect of a 12-month randomized clinical trial of exercise on serum prolactin concentrations in postmenopausal women. Cancer Epidemiol.Biomarkers Prev. 2007 May;16(5):895-9.
  281. Il'yasova D, Colbert LH, Harris TB, Newman AB, Bauer DC, Satterfield S, Kritchevsky SB. Circulating levels of inflammatory markers and cancer risk in the health aging and body composition cohort. Cancer Epidemiol.Biomarkers Prev. 2005 Oct;14(10):2413-8.
  282. Wetmore CM, Ulrich CM. Mechanisms associating physical activity with cancer incidence: exercise and immune function. In: McTiernan A, editor. Cancer prevention and management through exercise and weight control. Boca Raton: CRC Press; 2006. p. 157-76.
  283. Esposito K, Pontillo A, Di PC, Giugliano G, Masella M, Marfella R, Giugliano D. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA 2003 Apr 9;289(14):1799-804.
  284. Jakobisiak M, Lasek W, Golab J. Natural mechanisms protecting against cancer. Immunol.Lett. 2003 Dec 15;90(2-3):103-22.
  285. Nieman DC. Exercise immunology: practical applications. Int.J.Sports Med. 1997 Mar;18 Suppl 1:S91-100.
  286. Martinez ME, Heddens D, Earnest DL, Bogert CL, Roe D, Einspahr J, Marshall JR, Alberts DS. Physical activity, body mass index, and prostaglandin E2 levels in rectal mucosa. J.Natl.Cancer Inst. 1999 Jun 2;91(11):950-3.
  287. Abrahamson PE, King IB, Ulrich CM, Rudolph RE, Irwin ML, Yasui Y, Surawicz C, Lampe JW, Lampe PD, Morgan A, et al. No effect of exercise on colon mucosal prostaglandin concentrations: a 12-month randomized controlled trial. Cancer Epidemiol.Biomarkers Prev. 2007 Nov;16(11):2351-6.

top of page

Continue to G8. Mental Health
Back to G6. Functional Health
Back to Physical Activity Guidelines Advisory Committee Report

HHS | Accessibility | Privacy Policy | Freedom of Information Act | Disclaimer | Contact Us

This page last updated on: 10/7/2008

Content for this site is maintained by the
Office of Disease Prevention & Health Promotion, U.S. Department of Health and Human Services.