title: MSH2 118T>C and MSH6 159C>T promoter polymorphisms and the risk of colorectal cancer.
abstract: The most important indicator of colorectal cancer (CRC) 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 CRC risk. We investigated whether promoter polymorphisms in DNA mismatch repair (MMR) genes MSH2 and MSH6 are associated with the risk of CRC. We genotyped 929 CRC patients and 1098 control subjects from Ontario, and 467 patients and 344 controls from Newfoundland and Labrador, for two promoter polymorphisms in the MMR genes MSH2 and MSH6 using the fluorogenic 5' nuclease assay. We used unconditional logistic regression to evaluate the association between each polymorphism and CRC after adjusting for age and sex. The associations between polymorphisms and tumor clinicopathological features were evaluated with a Pearson's chi-squared test or Fisher's exact test. All statistical tests were two sided. We observed strong associations between the MSH2 -118T>C polymorphism and family history of CRC 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 CRC patients in Ontario (for Amsterdam criteria I, and I and II combined, P = 0.003 and P = 0.0001, respectively). The MSH2 -118T>C polymorphism was associated with strong family history of CRC in Ontario patients.
authors.affiliation: Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario M5T 3L9, Canada.
authors.forename: Miralem
authors.initials: M
authors.lastname: Mrkonjic
authors.forename: Stavroula
authors.initials: S
authors.lastname: Raptis
authors.forename: Roger C
authors.initials: RC
authors.lastname: Green
authors.forename: Neerav
authors.initials: N
authors.lastname: Monga
authors.forename: Darshana
authors.initials: D
authors.lastname: Daftary
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Dicks
authors.forename: H Banfield
authors.initials: HB
authors.lastname: Younghusband
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Parfrey
authors.forename: Steven S
authors.initials: SS
authors.lastname: Gallinger
authors.forename: John R
authors.initials: JR
authors.lastname: McLaughlin
authors.forename: Julia A
authors.initials: JA
authors.lastname: Knight
authors.forename: Bharati
authors.initials: B
authors.lastname: Bapat
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D000074081:MutS Homolog 3 Protein; D009523:Newfoundland and Labrador; D009864:Ontario; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
chemical_list: D004268:DNA-Binding Proteins; C078444:MSH3 protein, human; D000074081:MutS Homolog 3 Protein; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein