Cargando…
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...
Autores principales: | , , , , |
---|---|
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 |
_version_ | 1782233554687623168 |
---|---|
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. |
format | Online Article Text |
id | pubmed-3356375 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT vogelsangmatjaz thecumulativeeffectsofpolymorphismsinthednamismatchrepairgenesandtobaccosmokinginoesophagealcancerrisk AT wangyabing thecumulativeeffectsofpolymorphismsinthednamismatchrepairgenesandtobaccosmokinginoesophagealcancerrisk AT vebernika thecumulativeeffectsofpolymorphismsinthednamismatchrepairgenesandtobaccosmokinginoesophagealcancerrisk AT mwapaghalamechm thecumulativeeffectsofpolymorphismsinthednamismatchrepairgenesandtobaccosmokinginoesophagealcancerrisk AT parkermiqbal thecumulativeeffectsofpolymorphismsinthednamismatchrepairgenesandtobaccosmokinginoesophagealcancerrisk AT vogelsangmatjaz cumulativeeffectsofpolymorphismsinthednamismatchrepairgenesandtobaccosmokinginoesophagealcancerrisk AT wangyabing cumulativeeffectsofpolymorphismsinthednamismatchrepairgenesandtobaccosmokinginoesophagealcancerrisk AT vebernika cumulativeeffectsofpolymorphismsinthednamismatchrepairgenesandtobaccosmokinginoesophagealcancerrisk AT mwapaghalamechm cumulativeeffectsofpolymorphismsinthednamismatchrepairgenesandtobaccosmokinginoesophagealcancerrisk AT parkermiqbal cumulativeeffectsofpolymorphismsinthednamismatchrepairgenesandtobaccosmokinginoesophagealcancerrisk |