MICROSATELLITE INSTABILITY IN HUMAN COLONIC-CANCER IS NOT A USEFUL CLINICAL INDICATOR OF FAMILIAL COLORECTAL-CANCER

Background & Aims: Microsatellite instability is a property of most tu mors occurring in the context of hereditary nonpolyposis colon cancer. Instability also occurs in 10%-15% of apparently sporadic colorectal cancers, and it has been hypothesized that this instability may indica te a genetic predisposition to colonic cancer. This study evaluated wh ether there is a clinically useful association between colon cancer in stability and a family history of cancer. Methods: Colon cancer cases (n = 188) from a population-based study were evaluated for microsatell ite instability with 10 polymerase chain reaction primer sets. Instabi lity results were compared with family history and other clinical and biological characteristics. Results: Microsatellite instability was fo und in 16.5% of tumors. It was predominantly a feature of right-sided tumors (P = 0.003) and was associated with the youngest and oldest age s at diagnosis (P = 0.01). Instability was not associated with family history of cancer, sex of the individual, or the glutathione-S-transfe rase mu 1 null genotype. Conclusions: Although some very small, and as yet undefined, proportion of colon cancer may be caused by inherited mutations leading to microsatellite instability, tumoral instability b y itself is not a marker for familiality and should not be considered as evidence for an inherited syndrome.