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The Cumulative Effects of Polymorphisms in the DNA Mismatch Repair Genes and Tobacco Smoking in Oesophageal Cancer Risk

The DNA mismatch repair (MMR) enzymes repair errors in DNA that occur during normal DNA metabolism or are induced by certain cancer-contributing exposures. We assessed the association between 10 single-nucleotide polymorphisms (SNPs) in 5 MMR genes and oesophageal cancer risk in South Africans. Prio...

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Autores principales: Vogelsang, Matjaz, Wang, Yabing, Veber, Nika, Mwapagha, Lamech M., Parker, M. Iqbal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3356375/
https://www.ncbi.nlm.nih.gov/pubmed/22623965
http://dx.doi.org/10.1371/journal.pone.0036962
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author Vogelsang, Matjaz
Wang, Yabing
Veber, Nika
Mwapagha, Lamech M.
Parker, M. Iqbal
author_facet Vogelsang, Matjaz
Wang, Yabing
Veber, Nika
Mwapagha, Lamech M.
Parker, M. Iqbal
author_sort Vogelsang, Matjaz
collection PubMed
description The DNA mismatch repair (MMR) enzymes repair errors in DNA that occur during normal DNA metabolism or are induced by certain cancer-contributing exposures. We assessed the association between 10 single-nucleotide polymorphisms (SNPs) in 5 MMR genes and oesophageal cancer risk in South Africans. Prior to genotyping, SNPs were selected from the HapMap database, based on their significantly different genotypic distributions between European ancestry populations and four HapMap populations of African origin. In the Mixed Ancestry group, the MSH3 rs26279 G/G versus A/A or A/G genotype was positively associated with cancer (OR = 2.71; 95% CI: 1.34–5.50). Similar associations were observed for PMS1 rs5742938 (GG versus AA or AG: OR = 1.73; 95% CI: 1.07–2.79) and MLH3 rs28756991 (AA or GA versus GG: OR = 2.07; 95% IC: 1.04–4.12). In Black individuals, however, no association between MMR polymorhisms and cancer risk was observed in individual SNP analysis. The interactions between MMR genes were evaluated using the model-based multifactor-dimensionality reduction approach, which showed a significant genetic interaction between SNPs in MSH2, MSH3 and PMS1 genes in Black and Mixed Ancestry subjects, respectively. The data also implies that pathogenesis of common polymorphisms in MMR genes is influenced by exposure to tobacco smoke. In conclusion, our findings suggest that common polymorphisms in MMR genes and/or their combined effects might be involved in the aetiology of oesophageal cancer.
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spelling pubmed-33563752012-05-23 The Cumulative Effects of Polymorphisms in the DNA Mismatch Repair Genes and Tobacco Smoking in Oesophageal Cancer Risk Vogelsang, Matjaz Wang, Yabing Veber, Nika Mwapagha, Lamech M. Parker, M. Iqbal PLoS One Research Article The DNA mismatch repair (MMR) enzymes repair errors in DNA that occur during normal DNA metabolism or are induced by certain cancer-contributing exposures. We assessed the association between 10 single-nucleotide polymorphisms (SNPs) in 5 MMR genes and oesophageal cancer risk in South Africans. Prior to genotyping, SNPs were selected from the HapMap database, based on their significantly different genotypic distributions between European ancestry populations and four HapMap populations of African origin. In the Mixed Ancestry group, the MSH3 rs26279 G/G versus A/A or A/G genotype was positively associated with cancer (OR = 2.71; 95% CI: 1.34–5.50). Similar associations were observed for PMS1 rs5742938 (GG versus AA or AG: OR = 1.73; 95% CI: 1.07–2.79) and MLH3 rs28756991 (AA or GA versus GG: OR = 2.07; 95% IC: 1.04–4.12). In Black individuals, however, no association between MMR polymorhisms and cancer risk was observed in individual SNP analysis. The interactions between MMR genes were evaluated using the model-based multifactor-dimensionality reduction approach, which showed a significant genetic interaction between SNPs in MSH2, MSH3 and PMS1 genes in Black and Mixed Ancestry subjects, respectively. The data also implies that pathogenesis of common polymorphisms in MMR genes is influenced by exposure to tobacco smoke. In conclusion, our findings suggest that common polymorphisms in MMR genes and/or their combined effects might be involved in the aetiology of oesophageal cancer. Public Library of Science 2012-05-18 /pmc/articles/PMC3356375/ /pubmed/22623965 http://dx.doi.org/10.1371/journal.pone.0036962 Text en Vogelsang et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Vogelsang, Matjaz
Wang, Yabing
Veber, Nika
Mwapagha, Lamech M.
Parker, M. Iqbal
The Cumulative Effects of Polymorphisms in the DNA Mismatch Repair Genes and Tobacco Smoking in Oesophageal Cancer Risk
title The Cumulative Effects of Polymorphisms in the DNA Mismatch Repair Genes and Tobacco Smoking in Oesophageal Cancer Risk
title_full The Cumulative Effects of Polymorphisms in the DNA Mismatch Repair Genes and Tobacco Smoking in Oesophageal Cancer Risk
title_fullStr The Cumulative Effects of Polymorphisms in the DNA Mismatch Repair Genes and Tobacco Smoking in Oesophageal Cancer Risk
title_full_unstemmed The Cumulative Effects of Polymorphisms in the DNA Mismatch Repair Genes and Tobacco Smoking in Oesophageal Cancer Risk
title_short The Cumulative Effects of Polymorphisms in the DNA Mismatch Repair Genes and Tobacco Smoking in Oesophageal Cancer Risk
title_sort cumulative effects of polymorphisms in the dna mismatch repair genes and tobacco smoking in oesophageal cancer risk
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3356375/
https://www.ncbi.nlm.nih.gov/pubmed/22623965
http://dx.doi.org/10.1371/journal.pone.0036962
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