title: The cumulative effects of polymorphisms in the DNA mismatch repair genes and tobacco smoking in oesophageal cancer risk.
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 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.
authors.affiliation: 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.
authors.forename: Matjaz
authors.initials: M
authors.lastname: Vogelsang
authors.forename: Yabing
authors.initials: Y
authors.lastname: Wang
authors.forename: Nika
authors.initials: N
authors.lastname: Veber
authors.forename: Lamech M
authors.initials: LM
authors.lastname: Mwapagha
authors.forename: M Iqbal
authors.initials: MI
authors.lastname: Parker
mesh_terms: D044383:Black People / Q000235:genetics; D016022:Case-Control Studies; D045643:DNA Repair Enzymes / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D056726:Genetic Association Studies; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D013019:South Africa / Q000453:epidemiology; D044465:White People / Q000235:genetics
chemical_list: D045643:DNA Repair Enzymes