Are There Genetic Underpinnings of Cancer Disparities?

Map of NCIs Cancer Surveillance Sites

Map of NCI's Cancer Surveillance Sites

Since sequencing of the human genome was completed in 2001, scientists have found that people are more alike than they are different. However, certain genetic factors, like susceptibility to disease, can vary from one population to another. This month, BenchMarks discusses how inherent genomic variations can provide new insight into the genetic underpinnings of cancer.

Cancer Disparities

For decades, scientists have observed that some racial and ethnic groups in the U.S. bear a heavier burden of disease than others. According to the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute (NCI), African American men are nearly 56 percent more likely to develop prostate cancer than white men, and at a younger age. Furthermore, once diagnosed with prostate cancer, African Americans are more than twice as likely as white men to die of the disease. While more data exists for African Americans, similar disparities exist in other cancers and for other minority groups.

What drives this inequality? Scientists at NCI and elsewhere are investigating the underlying causes of cancer disparities. There are hundreds of environmental variables that differ between groups of people, such as economic status, access to health care and health insurance, education, social inequalities, cultural barriers, and cultural traditions that affect behaviors like smoking. Any combination of factors may influence a person’s risk of cancer.

Even accounting for factorslikeincome, education, and insurance, discrepancies in cancer rates still exist between racial and ethnic groups, pointing to a role for genetics in the basis for disproportionate disease burden. However, using race as a factor in explaining the biology of disease is controversial. Race and ethnicity are often used to categorize people based on shared characteristics such as physical features, culture, and language. Moreover, race is viewed by some as a social classification of people, not a scientific designation.

Race and Genetics

Indeed, genomic mapping has shown that race means very little when it comes to genetic variation. “If you look at random genotypes from an individual, it is impossible to categorize them into ethnic categories,” explained Matthew Freedman, M.D., cancer genetics researcher at the Dana-Farber Cancer Institute in Boston, Mass.

Genetic variation in a population is usually measured by estimating the number of differences in the DNA sequence between two inherited copies of a gene. Using this method, scientists estimate there are 10 million to 11 million genetic variations (in the form of single base changes) in the human population. Out of all these variants, only one variant, which helps determine susceptibility to malaria, is known to exist in one form in African descendents and in a different form in European descendents. Research has unequivocally shown that most genetic variation occurs within ethnic groups (93 percent to 95 percent) rather than between ethnic groups (three percent to five percent). 

Although genomic diversity is greatest within a group, predispositions to diseases like sickle cell anemia in African Americans, and Tay-Sachs disease in Ashkenazi Jews, are well known.  However, these diseases are the result of geographic origin, patterns of inheritance, and selective pressure by environmental factors, rather than the result of genetic differences inherent in all members of a particular group. There is a distinction between rare mutations with strong correlations to diseases, like Tay-Sachs, and common variants in a population that more modestly impact risk. Variations can be found in all types of people, but at different frequencies in different ethnic groups, and are thought to be the most common basis for disease. Yet they are also the more difficult genetic factors to detect. 

In a search for common variants associated with prostate cancer, Freedman used the power of the Multiethnic Cohort Study (MEC) at the University of Southern California and the University of Hawaii. In 1993, the MEC enrolled over 215,000 African American, Latino, Asian, and white men and women to track links between risk of cancer and environmental factors, such as diet, demographics, and family disease history.

The unusually large size of the MEC study, coupled with admixture mapping—a new technique for tracing variants that differ in frequency across populations—provided Freedman and his colleagues with the opportunity to sift for genetic clues in the genomes of nearly 1,600 African American men with prostate cancer and over 850 cancer-free African American men. By doing so, they found that a segment of chromosome 8 containing nine known genes can account for a substantial portion of the increased prostate cancer risk observed in African American men under the age of 72.

Genetics in Cancer Prevention and Treatment

Other types of cancer also disproportionately affect African Americans. Death rates due to breast cancer are decreasing over the entire U.S. population, but African American women are still more likely to die of the disease than white women. If race had not been taken into account when examining these statistics, then it might have been assumed that reductions in breast cancer mortality applied to everyone.

“Even though race is a social concept, it is still an important issue for other reasons,” said Claudia Baquet, M.D., M.P.H., professor and director at the University of Maryland Comprehensive Center for Health Disparities in Balto., Md. “Examining breast cancer rates by race, for example, allows us to identify the populations that are not benefiting from the advances in breast cancer therapy at the same rate as the general population. These data are important for designing new therapies and prevention strategies which benefit high risk disparity populations.”

Understanding differences in the underlying genetics responsible for different types of cancers might also influence treatment options. For example, the breast cancer drug tamoxifen acts by blocking the ability of estrogen hormones to promote the growth of breast tissue. Tamoxifen is most effective for women with breast cancer that tests positive for the estrogen receptor. Yet a higher proportion of African American women than white women are estrogen receptor-negative. Thus, the use of standard therapies based on the presence of hormone receptors may be ineffective for some African American women.

Valuable Research

The roots of cancer are multi-factorial and complex. Genetic variations alone rarely cause cancer, but teasing out discrepancies will help reveal the big picture of how cancer works. Any research that hunts out a genetic factor that will stop the progression of cancer, while benefiting the populations that have the disparity, will ultimately benefit all cancer patients.

“We’re entering a stage of research where we want to explore genes, the environment, and the interactions between them, because we think both sides of the equation will prove to be important,” commented Freedman. “Taking all factors into account will hopefully provide a comprehensive view of the cancer.”

Baquet concluded, “No matter who the patient is, understanding biological underpinnings of cancer and gene-environment interactions is essential to our efforts to eliminate cancer disparities.”

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