Hereditary colorectal cancer

Colorectal cancer (CRC) is one of the most significant causes of cancer morbidity and mortality in the United States. CRC incidence rates increase with age with greater than 90 % of cases occurring in persons over the age of 50. Twin and family studies have shown that genetic risk factors influence CRC incidence in up to 35 % of cases, but within that 35 % the level of risk conferred by genetic factors that predispose to CRC varies enormously. The correlations between family history and CRC susceptibility are propelled by a range of genetic mechanisms, from high-risk, disease-causing mutations that ablate gene function to low-risk genetic variants that perturb gene function in subtler ways. In addition, genetic risk factors can interact with each other and with nongenetic factors to increase or decrease CRC risk. However, the impact of interaction on risk is poorly understood.