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Patient and Tumor Characteristics of Colon Cancers with Microsatellite Instability: A Population-based Study¹

New Mexico Tumor Registry [A. C., N. S., C. K.], Center for Molecular and Cellular Diagnostics [C. W., I-M. C., J. R., D. V.], and Department of Pathology [N. J.], University of New Mexico, Albuquerque, New Mexico 87131; Department of Preventive Medicine, University of Southern California, Los Angeles, California 90033 [F. G.]; Saint Joseph Healthcare Systems [P. D.], Lovelace Medical Center [R. M.], Department of Veterans Affairs Medical Center [R. H.], and Presbyterian Healthcare Services [E. F.], Albuquerque, New Mexico 87125

Molecular screening for microsatellite instability (MSI) in colon cancers has been proposed to identify individuals with hereditary nonpolyposis colorectal cancer. To date, most reports of MSI in colorectal cancer have been based on studies of clinical case series or high-risk families. We examined the proportion of incident colon cancers in the general population that exhibit MSI by patient and tumor characteristics. We interviewed 201 colon cancer cases ascertained by the New Mexico Tumor Registry in the metropolitan Albuquerque area for demographic information, lifestyle factors, medical history, and family cancer history. Paired normal and tumor tissue specimens were obtained for each case. Three microsatellite markers were used; instability was defined as observed alteration at two or more loci. Overall, 37 of 201 (18%) colon cancers exhibited instability. MSI was more common among cases >70 years (26%) and most common among cases >80 years (38%). MSI was significantly associated with tumors in the proximal colon and with later stage and poor differentiation among cases >70 years. MSI was not associated with a history of polyps. Family history of colorectal cancer was associated with MSI only among cases <50 years. When all factors were analyzed jointly in a regression model, proximal subsite and poor differentiation remained significantly associated with MSI. One patient, whose tumor exhibited MSI, fulfilled the Amsterdam Criteria for hereditary nonpolyposis colorectal cancer. Our study provides a population-based estimate of MSI in colon tumors and a representative estimate of the proportion of colorectal cancer patients in the general population who consent to be interviewed for family cancer history and to have biological samples analyzed.

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