Association of body mass, smoking and microsatellite status in colorectal cancer: A population-based case-control study (DACHS)

Abstract

Introduction: Colorectal cancer is a heterogeneous disease with different pathologic subtypes. In recent studies, body mass index (BMI) was associated with an increased risk of microsatellite-stable (MSS) tumors, but not with microsatellite-instable (MSI-high) tumors. However, after stratification for gender, results were not consistent. Thus, we analysed the association of common risk factors of colorectal cancer with MSI. Methods: We conducted a population-based case-control study in the Rhine-Neckar region (DACHS study), including 1262 patients with colorectal cancer and 1891 controls. MSI status in colorectal cancer was determined by immunohistological evaluation of MSH2 and MLH1 in tissue microarrays (TMAs). Information on weight and height (BMI), smoking and other risk or protective factors of colorectal cancer were obtained in standardized in-person interviews. Multiple logistic regression analyses were performed to investigate the association of BMI and smoking with microsatellite status. Results: In TMAs of 1262 patients, we identified 951 MSS tumors (75%) and 109 MSI-high (9%). 203 tumors (16%) were not classifiable. MSS tumors were more often prevalent in the distal colorectum (69%), and MSI-high tumors more often prevalent in the proximal colon (79%). There was a strong association of BMI ≥30kg/m2 with MSI-high tumors among women (adjusted odds ratio 3.50, 95% confidence interval 1.66–7.36), but not among men (OR 1.01, 0.43–2.34). Obesity was associated with a slight, however non-significant increase in the risk of MSS tumors (OR 1.16, 0.91–1.47). Smoking was associated with higher risk of MSS tumors (OR 1.26, 1.05–1.51), but not of MSI-high tumors (OR 1.07, 0.69–1.66). Conclusions: Unlike previous studies, we found a strong association of obesity with MSI-high tumors in women. The underlying reasons for the patterns observed deserve further investigation and will be discussed at the congress.