Body mass index and microsatellite instability in colorectal cancer: a population-based study.

BACKGROUND Previous studies reported a positive association of body mass index (BMI) with microsatellite-stable (MSS) but not with microsatellite-instable (MSI-high) colorectal cancer. However, information from population-based studies conducted in representative age groups is so far limited. METHODS We conducted a population-based case-control study (DACHS) in Southern Germany, including 1,215 patients with incident colorectal cancer and 1,891 matched controls with no upper age limit. Information on risk factors of colorectal cancer was obtained in standardized interviews. Microsatellite instability was analyzed using a mononucleotide marker panel. RESULTS Median age among cases was 69 years, and 115 cases were classified MSI-high (9.5%). In multivariate analyses, BMI was positively associated with both risk of MSI-high colorectal cancer [per 5 kg/m(2): OR, 1.71; 95% confidence interval (CI), 1.35-2.17] and risk of MSS colorectal cancer (OR, 1.20; 95% CI, 1.07-1.33). The association with MSI-high colorectal cancer was limited to women (OR, 2.04; 95% CI, 1.50-2.77; P interaction = 0.02) and most pronounced among ever users of postmenopausal hormone replacement therapy (OR, 4.68; 95% CI, 2.36-9.30; P interaction = 0.01). In case-only analyses, BMI was more strongly associated with MSI-high colorectal cancer than with MSS colorectal cancer among women (OR, 1.84; 95% CI, 1.13-1.82; P interaction = 0.01). CONCLUSIONS This population-based study confirms previous findings of increased risk of MSS colorectal cancer with obesity between both sexes and suggests that overweight and obesity may also be associated with increased risk of MSI-high colorectal cancer among women. IMPACT These findings extend available data on the association of BMI and microsatellite instability in colorectal cancer and may suggest a link between overweight and obesity with sporadic MSI-high colorectal cancer in women.