The cumulative effects of polymorphisms in the DNA mismatch repair genes and tobacco smoking in oesophageal cancer risk

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dc.contributor.authorVogelsang, Matjazen_ZA
dc.contributor.authorWang, Yabingen_ZA
dc.contributor.authorVeber, Nikaen_ZA
dc.contributor.authorMwapagha, Lamech Men_ZA
dc.contributor.authorParker, M Iqbalen_ZA
dc.date.accessioned2016-01-11T06:55:07Z
dc.date.available2016-01-11T06:55:07Z
dc.date.issued2012en_ZA
dc.description.abstractThe 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.en_ZA
dc.identifier.apacitationVogelsang, M., Wang, Y., Veber, N., Mwapagha, L. M., & Parker, M. I. (2012). The cumulative effects of polymorphisms in the DNA mismatch repair genes and tobacco smoking in oesophageal cancer risk. <i>PLoS One</i>, http://hdl.handle.net/11427/16293en_ZA
dc.identifier.chicagocitationVogelsang, Matjaz, Yabing Wang, Nika Veber, Lamech M Mwapagha, and M Iqbal Parker "The cumulative effects of polymorphisms in the DNA mismatch repair genes and tobacco smoking in oesophageal cancer risk." <i>PLoS One</i> (2012) http://hdl.handle.net/11427/16293en_ZA
dc.identifier.citationVogelsang, M., Wang, Y., Veber, N., Mwapagha, L. M., & Parker, M. I. (2012). The cumulative effects of polymorphisms in the DNA mismatch repair genes and tobacco smoking in oesophageal cancer risk. PLoS One, 7(5), e36962. doi:10.1371/journal.pone.0036962en_ZA
dc.identifier.ris TY - Journal Article AU - Vogelsang, Matjaz AU - Wang, Yabing AU - Veber, Nika AU - Mwapagha, Lamech M AU - Parker, M Iqbal AB - 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. DA - 2012 DB - OpenUCT DO - 10.1371/journal.pone.0036962 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2012 T1 - The cumulative effects of polymorphisms in the DNA mismatch repair genes and tobacco smoking in oesophageal cancer risk TI - The cumulative effects of polymorphisms in the DNA mismatch repair genes and tobacco smoking in oesophageal cancer risk UR - http://hdl.handle.net/11427/16293 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16293
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0036962
dc.identifier.vancouvercitationVogelsang M, Wang Y, Veber N, Mwapagha LM, Parker MI. The cumulative effects of polymorphisms in the DNA mismatch repair genes and tobacco smoking in oesophageal cancer risk. PLoS One. 2012; http://hdl.handle.net/11427/16293.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDivision of Medical Biochemistryen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis 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 credited.en_ZA
dc.rights.holder© 2012 Vogelsang et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherSmoking habitsen_ZA
dc.subject.otherEsophageal canceren_ZA
dc.subject.otherAfricansen_ZA
dc.subject.otherHaplotypesen_ZA
dc.subject.otherDNA repairen_ZA
dc.subject.otherMultiple alignment calculationen_ZA
dc.subject.otherVariant genotypesen_ZA
dc.subject.otherAllelesen_ZA
dc.titleThe cumulative effects of polymorphisms in the DNA mismatch repair genes and tobacco smoking in oesophageal cancer risken_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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