MSH2 118T>C and MSH6 159C>T Promoter Polymorphisms and the Risk of Colorectal Cancer

• Published in: Carcinogenesis
• Main Authors: Mrkonjic, Miralem, Raptis, Stavroula, Green, Roger C., Monga, Neerav, Daftary, Darshana, Dicks, Elizabeth, Younghusband, H. Banfield, Parfrey, Patrick S., Gallinger, Steven S., McLaughlin, John R., Knight, Julia A., Bapat, Bharati
• Format: Text
• Language: English
• Published: Oxford University Press 2007
• Subjects: MOLECULAR EPIDEMIOLOGY; Newfoundland
• Online Access: http://carcin.oxfordjournals.org/cgi/content/short/bgm229v1; https://doi.org/10.1093/carcin/bgm229

Background and Aims : The most important indicator of colorectal cancer risk is the presence of family history of the disease. Inherited genetic changes, such as single nucleotide polymorphisms, in key candidate genes may contribute to colorectal cancer risk. We investigated whether promoter polymorphisms in DNA mismatch repair genes MSH2 and MSH6 are associated with the risk of colorectal cancer. Methods: We genotyped 929 colorectal cancer patients and 1098 control subjects from Ontario, and 467 patients and 344 controls from Newfoundland and Labrador, for two promoter polymorphisms in the mismatch repair genes MSH2 and MSH6 using the fluorogenic 5′ nuclease assay. We used unconditional logistic regression to evaluate the association between each polymorphism and colorectal cancer after adjusting for age and sex. The associations between polymorphisms and tumor clinicopathologic features were evaluated with a Pearson's chi-squared or Fisher's exact test. All statistical tests were two-sided. Results: We observed strong associations between the MSH2 -118T>C polymorphism and family history of colorectal cancer, based on the Amsterdam criteria I ( P =0.005), and Amsterdam criteria I and II ( P =0.036) among cases from Ontario. This association was especially evident among female colorectal cancer patients in Ontario (for Amsterdam criteria I, and I and II combined, P =0.003 and P =0.0001, respectively). Conclusion: The MSH2 -118T>C polymorphism was associated with strong family history of colorectal cancer in Ontario patients.