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Molecular Epidemiology of Cancer

Dr. Chen is Research Fellow, Brigham and Women’s Hospital, Department of Medicine, Harvard Medical School, Boston, MA.
Dr. Hunter is Director, Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, MA.

Epidemiology is very successful in identifying environmental and lifestyle factors that increase or reduce risk of specific cancers, leading to cancer prevention strategies. However, the etiology of many types of cancer is still poorly understood, despite extensive use of questionnaires and interview-based approaches in conventional epidemiologic studies. The integration of molecular techniques into epidemiology studies may provide new insights and has been referred to as molecular epidemiology. For instance, our ability to make connections between lifestyle and cancer risk is limited by difficulty in accurately measuring exposure to many carcinogens—newer molecular markers of exposure may provide better information. The completion of the Human Genome Project gives us knowledge of the genetic variations that presumably underlie the fact that a family history of cancer is a risk factor for most cancer types. Some of this excess risk has been explained over the last decade by identification of mutations in genes that give rise to a very high familial risk. Molecular epidemiologists are searching for genes that may give rise to much smaller increases in individual risk, but account for much of the residual risk associated with family history. These genes may also interact with environment and lifestyle factors such that cancer risk is not equally elevated in all persons exposed to an environmental factor (but not genetically susceptible), or all gene carriers (but not exposed to the environmental factor). Molecular markers may help to differentiate tumors with the same histologic appearance into different etiologic subtypes. Finally, response to treatment may be determined by molecular subtypes of the tumor, or inherited variation in drug metabolism. Examples will be given of how use of molecular techniques is informative in epidemiological studies of cancer and is predicted to lead to improvements in cancer incidence, early detection, and mortality.

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