Combination of DNA repair gene single nucleotide polymorphisms and increased levels of DNA adducts in a population-based study

摘要: Inherited single nucleotide polymorphisms (SNPs) of DNA repair genes may contribute to variations in capacity and susceptibility cancer. We investigated the role SNPs three ( X-ray cross-complementing group 1-Arg399Gln , exon 10; 3-Thr241Met 7; xeroderma pigmentosum-D-Lys751Gln 23) their combination, modulating levels “bulky” adducts a population sample 628 Italian healthy individuals belonging prospective European project “European Prospective Investigation into Cancer Nutrition.” DNA-adduct were measured as relative adduct level per 109 nucleotides by 32P-post labeling assay WBCs from peripheral blood. Genotyping was performed PCR-RFLP analysis or primer extension/denaturing high-performance liquid chromatography technique. found dose-response relationship between number at-risk alleles P = 0.0046). Individuals with at least variant had statistically significant odds ratio (OR) for being highest tertile compared those undetectable [three alleles, adjusted OR 5.07, 95% confidence interval (CI) 1.29–19.9; four 5.03, CI 1.18–21.45; five 7.65, 0.94–62.2]. Our study suggests that combined effect multiple be more important than investigation SNP capacity.