In recent months, 2 genes were identified for the common form of hereditary colorectal cancer (hereditary non-polyposis colon cancer; HNPCC). Based on small numbers of highly selected families, as much as 90% of HNPCC might be attributable to these genes and carriers have an estimated 70-90% lifetime risk of colorectal cancer. However, HNPCC accounts for 4% or less of all colorectal cancers. The frequency of inherited MSH2 and MLH1 mutations is unknown among the other 96% of all colorectal cancers. Therefore, the aims of this population-based epidemiological study are to determine the frequencies of germline MSH2 and MLH1 mutations (carriers) in a population-based, stratified sample of 400 colorectal cancer patients randomly selected from the Cancer Surveillance Program of Orange, Imperial and San Diego Counties, California. Study subjects will be sampled from strata defined by family history of colorectal cancer (hereditary non-polyposis colon cancer, familial cases but not HNPCC, and sporadic cases), and age at cancer diagnosis (0-64 years, and 65 years and over). The results of mutational status (its presence or absence, and mutation site and type within the MSH2/MSH1 genes) will be correlated with data collated on family history, age at diagnosis, and RER status, as well as clinical, demographic and risk factor data from the questionnaire interview. The data from this population-based study will facilitate strategic planning for translation cancer control research that targets family members of subsets of colorectal cancer cases.
