Microsatellite instability in human colonic cancer is not a useful clinical indicator of familial colorectal cancer.
OBJECTIVE
Microsatellite instability is a property of most tumors 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 indicate a genetic predisposition to colonic cancer. This study evaluated whether there is a clinically useful association between colon cancer instability and a family history of cancer.


METHODS
Colon cancer cases (n = 188) from a population-based study were evaluated for microsatellite instability with 10 polymerase chain reaction primer sets. Instability results were compared with family history and other clinical and biological characteristics.


RESULTS
Microsatellite instability was found 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 ages at diagnosis (P = 0.01). Instability was not associated with family history of cancer, sex of the individual, or the glutathione-S-transferase 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 by itself is not a marker for familiality and should not be considered as evidence for an inherited syndrome.
D000328:Adult; D000368:Aged; D001483:Base Sequence; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003110:Colonic Neoplasms / Q000201:enzymology / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D005192:Family Health; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests
D005982:Glutathione Transferase