ABSTRACT
This chapter discusses hereditary colorectal cancer disorders that have been characterized to date and the implications for clinical practice. It describes low-penetrance alleles that, collectively, are likely to contribute more to overall colorectal cancer incidence than the known dominant disorders. Heritable genetic defects make a major contribution to the overall incidence of colorectal cancer. Systematic analysis of DNA mismatch repair mutation carriers in the population has shown that there is a 74% risk of developing colorectal cancer for males and 30% risk for females. With greater clinical awareness and predictive genetic testing, the majority of cases are detected early and undergo prophlylactic colectomy; less than 0.07% of colorectal carcinoma incident cases are attributed to familial adenomatous polyposis. A number of genetic polymorphisms have been identified in genes that are known to be involved in the metabolism of polycyclic aromatic hydrocarbons and other tobacco-related carcinogens.
