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.pdf

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.