Associations between cigarette smoking, lifestyle factors, and microsatellite instability in colon tumors

Background: Microsatellite instability (MSI) has been reported to occur in approximately 10%-15% of colon tumors. MSI is characterized by the presence of mutations in tandemly repeated DNA sequences known as microsatellites. Some individuals with unstable tumors have inherited mutations in mismatch repair genes, but MSI is also observed in sporadic colon cancer. It is unkn own whether lifestyle factors associated with colon cancer, such as physica l activity, body size, cigarette smoking, or use of aspirin and/or nonstero idal anti-inflammatory drugs, contribute to MSI in sporadic tumors. Methods : Data from a population-based, case-control study of colon cancer were use d. Case subjects were between 30 and 79 years of age at the time of diagnos is and included both men and women. Questionnaire data were used to obtain information on lifestyle factors. Tumor MSI was determined with the use of a panel of 10 tetranucleotide repeats and two mononucleotide repeats. A tot al of 1510 case subjects had valid questionnaire data and tumor DNA from wh ich we were able to obtain MSI status. Questionnaire data were compared wit h lifestyle factors reported by 2410 population-based control subjects. All statistical tests were two-sided. Results: MSI-positive (MSI+) tumors were most common in older people and women and in the proximal colon. Patients with MSI+ tumors were more likely to smoke 20 or more cigarettes a day than case subjects with MSI-negative (MSI-) tumors (odds ratio for being a smok er = 1.6 [95% confidence interval = 1.0-2.5] for men and 2.2 [95% confidenc e interval = 1.4-3.5] for women). The association between MSI+ tumors and c igarette smoking was strongest among case subjects who started to smoke at a young age, smoked for 35 or more years, and were either current smokers o r had stopped fewer than 15 years before diagnosis. A statistically signifi cant linear trend of increased risk of MSI+ tumors was observed with increa sing amount smoked (P<.01), Conclusions: This study suggests that smoking c igarettes statistically significantly contributes to MSI in colon tumors, W e estimate that approximately 21% of MSI in colon tumors may be attributabl e to cigarette smoking.