Familial risk factors are known to play an important role in colorectal cancer (CRC) risk, particularly when the relatives are affected by early-onset cancer. Part of this familial aggregation can be accounted for by inherited forms of colorectal cancer, i.e. familial adenomatous polyposis (less than 1% of all CRC) and hereditary nonpolyposis colorectal cancer (about 3%). Other genetic factors may be involved in the development of adenoma or in the transformation of adenoma into carcinoma. That the existence of polymorphisms of the adenomatous polyposis coli gene increase susceptibility to both adenomas and cancer favours this hypothesis. Interactions between environmental factors, and most of all dietary factors, and polymorphisms of carcinogen-metabolizing enzymes may also be involved. Better knowledge of these mechanisms will substantially widen the scope of colorectal cancer prevention.