Cancer population genetics and tumour prevention: an unfulfilled paradigm

The molecular approach to cancer has identified specific abnormalities that contribute to malignant pathogenesis in an aetiological manner and define individuals who are at higher risk for specific malignancies. Studies of cancer distribution in families suggest that 15-20% of all malignancies may have a significant germ line hereditable mutation that directly or indirectly contributes to tumour development. Additionally, the identification of many genetically-determined polymorphisms that regulate carcinogen metabolism indicate that their assessment may contribute to selecting individuals for preventive surveillance or intervention as well. Locating individuals in the population who have moderate to high risk germ line mutations in critical oncogenic regulatory genes and assessing a panel of polymorphisms that underlie a significant attributable risk for cancer development may allow the recruitment of individuals at high risk for a particular malignancy and, therefore, represent good candidates for either directed organ surveillance and/or chemoprevention trials.