MSH2 −118T>C and MSH6 −159C>T promoter polymorphisms and the risk of colorectal cancer
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...
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| Veröffentlicht in: | Carcinogenesis (New York) 2007-12, Vol.28 (12), p.2575-2580 |
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| creator | 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 |
| description | 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. |
| doi_str_mv | 10.1093/carcin/bgm229 |
| format | Article |
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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.</description><identifier>ISSN: 0143-3334</identifier><identifier>EISSN: 1460-2180</identifier><identifier>DOI: 10.1093/carcin/bgm229</identifier><identifier>PMID: 17942459</identifier><identifier>CODEN: CRNGDP</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Adult ; Aged ; Biological and medical sciences ; Carcinogenesis, carcinogens and anticarcinogens ; Case-Control Studies ; Colorectal Neoplasms - genetics ; DNA-Binding Proteins - genetics ; Female ; Gastroenterology. Liver. Pancreas. Abdomen ; Genetic Predisposition to Disease ; Humans ; Male ; Medical sciences ; Middle Aged ; MutS Homolog 2 Protein - genetics ; MutS Homolog 3 Protein ; Newfoundland and Labrador ; Ontario ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Stomach. Duodenum. Small intestine. Colon. Rectum. 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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.</description><subject>Adult</subject><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>Carcinogenesis, carcinogens and anticarcinogens</subject><subject>Case-Control Studies</subject><subject>Colorectal Neoplasms - genetics</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Female</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Genetic Predisposition to Disease</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>MutS Homolog 2 Protein - genetics</subject><subject>MutS Homolog 3 Protein</subject><subject>Newfoundland and Labrador</subject><subject>Ontario</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Promoter Regions, Genetic</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. 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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.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>17942459</pmid><doi>10.1093/carcin/bgm229</doi><tpages>6</tpages></addata></record> |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adult Aged Biological and medical sciences Carcinogenesis, carcinogens and anticarcinogens Case-Control Studies Colorectal Neoplasms - genetics DNA-Binding Proteins - genetics Female Gastroenterology. Liver. Pancreas. Abdomen Genetic Predisposition to Disease Humans Male Medical sciences Middle Aged MutS Homolog 2 Protein - genetics MutS Homolog 3 Protein Newfoundland and Labrador Ontario Polymorphism, Single Nucleotide Promoter Regions, Genetic Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Tumors |
| title | MSH2 −118T>C and MSH6 −159C>T promoter polymorphisms and the risk of colorectal cancer |
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