U.S National Institutes fo Health | cancer.gov NCI Logo

Cancer Intervention and Surveillance Modeling Network

Modeling to guide public health research and priorities

Other Achievements: Highlights

How do smoking habits influence the initiation and promotion of lung carcinogenesis?

A two-stage clonal expansion (TSCE) model was used to analyze data from five large cohorts. The TSCE model, which is based on the biological paradigm of initiation, promotion, and progression in carcinogenesis, recognizes that carcinogenesis is a process of mutation accumulation and clonal expansion of partially altered cells on the pathway to malignancy. The model may be used to generate biological hypotheses regarding the mechanism of tobacco-induced lung cancer and to explore the extent to which projected risks depend on the mechanism of smoking-induced lung cancer. The first study, using data from the British Doctors' cohort and two American Cancer Society Cohorts (Cancer Prevention Studies I and II), indicated that clonal expansion (promotion) of partially altered (initiated) cells by cigarette smoke is the dominant model mechanism (Hazelton 2005). A second study, based on analyses of data from the Nurses' Health and Health Professionals Follow-up Studies, confirmed these findings (Meza 2008). The second study showed also that lung cancer incidence among non-smokers, continuing smokers, and ex-smokers was similar in the two cohorts, suggesting that there is little difference in lung cancer risk between men and women, whether related to smoking or not. These two studies show that the importance of smoking duration on lung cancer risk is a direct consequence of smoking-related promotion.

Return to Top

How can the growth rates of lung cancers be estimated using data from incomplete observations?

Estimates of the growth rates of tumors based on two measurements, one of which is based on retrospective review of previous scans or films, are biased toward lower growth rates. Prospective tumor measurements can only occur, for ethical reasons, when the initial tumor is very small, and when it is thought to be benign, so it can be watched instead of being removed. Tumors found between screens (interval cases) tend to be enriched in faster growing tumors since they were so small at the previous screen that they were missed or they did not exist at all. A method was developed to estimate the population variability in tumor growth rate using data with selectively missing or selectively included observations (Gorlova 2005). Methods of this type are useful in making optimal use of available data to characterize the natural history of lung cancer.

Return to Top

What is the effect of state and national tobacco control programs in reducing smoking prevalence and tobacco-related mortality?

The Pacific Institute for Research and Evaluation CISNET lung model (SimSmoke) can be used to retrospectively estimate the impact of various tobacco control policies on observed declines in smoking rates and on tobacco-related mortality, as well as to project the potential effect of tobacco control policies in reducing these rates. The model was applied to estimate:

Results consistently showed that price increases and media policies had the largest impact on smoking rates, with substantially smaller components attributable to telephone quit lines, youth access policies, and clear air laws. Models of this type can assist policy makers at the state and national level by demonstrating the progress of specific states, explaining the policies that have contributed to those declines, and determining the potential impact of enhanced tobacco control efforts in other regions of the country.

Return to Top

What are the potential benefits associated with the use of low-nitrosamine smokeless tobacco products?

CISNET investigators from the Pacific Institute for Research and Evaluation convened expert panels to predict the mortality risks (Levy 2004) and impact on tobacco use (Levy, Mumford et al. 2006) in the United States of a "harm reduction" policy requiring that smokeless tobacco products meet low nitrosamine standards, but could be marketed with a warning label consistent with the evidence of relative health risks. The panel concluded that low-nitrosamine smokeless tobacco products may have a substantially lower risk than smoking, and that the new policy could produce a modest acceleration in the decline in smoking prevalence over 5 years. Efforts to quantify the impact of policies of this type provide starting values for tobacco control modeling efforts, and provide a basis to initiate the public policy debate.

Return to Top

What is the potential of screening high risk population based on their genetic susceptibility?

In a modeling study, Gorlova (2003) identified a subgroup of former, current, and never smokers at high risk for developing lung cancer based on their genetic susceptibility profiles. The study estimated the high-risk group’s lifetime probability of the disease and assessed the potential mortality reduction that could be achieved by screening. The high-risk group was defined as the 12.5% of the population above the third quartile for bleomycin sensitivity and below the median for DNA-repair capacity. Another modeling study (Deng 2008), using the two-stage clonal expansion stochastic model framework, investigated the role of both genetic susceptibility and smoking history in the initiation, clonal expansion, and malignant transformation processes in lung carcinogenesis, integrating information collected by a case-control study and a large-scale prospective cohort.

Return to Top