MSH2 −118T>C and MSH6 −159C>T promoter polymorphisms and the risk of colorectal cancer
Autor: | Neerav Monga, Steven S. Gallinger, Elizabeth Dicks, Roger C. Green, Stavroula Raptis, Miralem Mrkonjic, H. Banfield Younghusband, John R. McLaughlin, Darshana Daftary, Patrick S. Parfrey, Julia A. Knight, Bharati Bapat |
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Rok vydání: | 2007 |
Předmět: |
Adult
Male Oncology Cancer Research Candidate gene Amsterdam criteria medicine.medical_specialty Newfoundland and Labrador Single-nucleotide polymorphism Polymorphism Single Nucleotide Internal medicine Genotype medicine Humans Genetic Predisposition to Disease Family history Promoter Regions Genetic neoplasms Aged Ontario Genetics business.industry General Medicine Middle Aged digestive system diseases DNA-Binding Proteins MSH6 Exact test MutS Homolog 2 Protein MSH2 Case-Control Studies MutS Homolog 3 Protein Female Colorectal Neoplasms business |
Zdroj: | Carcinogenesis. 28:2575-2580 |
ISSN: | 1460-2180 0143-3334 |
Popis: | 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. |
Databáze: | OpenAIRE |
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