原创力文档the cumulative effects of polymorphisms in the dna mismatch repair genes and tobacco smoking in oesophageal cancer risk的累积影响dna错配修复基因的多态性和吸烟在食道癌的风险.pdfVIP
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the cumulative effects of polymorphisms in the dna mismatch repair genes and tobacco smoking in oesophageal cancer risk的累积影响dna错配修复基因的多态性和吸烟在食道癌的风险
The Cumulative Effects of Polymorphisms in the DNA
Mismatch Repair Genes and Tobacco Smoking in
Oesophageal Cancer Risk
1,2 1 1 1 1
Matjaz Vogelsang , Yabing Wang , Nika Veber , Lamech M. Mwapagha , M. Iqbal Parker *
1 International Centre for Genetic Engineering and Biotechnology, Cape Town Component, South Africa and Division of Medical Biochemistry, and IIDMM, University of
Cape Town, Cape Town, South Africa, 2 Department for Biosynthesis and Biotransformation, National Institute of Chemistry, Ljubljana, Slovenia
Abstract
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 r(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.
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