Genetic polymorphisms in DNA base‐excision repair genes ADPRT, XRCC1, and APE1 and the risk of squamous cell carcinoma of the head and neck

Abstract

Tobacco smoke contains numerous carcinogens that cause DNA damage, including oxidative lesions that are removed effectively by the base-excision repair (BER) pathway, in which adenosine diphosphate ribosyl transferase (ADPRT), x-ray repair cross-complementing 1 (XRCC1), and apurinic/apyimidinic endonuclease (APE1) play key roles. Genetic variations in the genes encoding for these DNA repair enzymes may alter their functions. Although there have been several studies that generated mixed results on the association between XRCC1 variants and the risk of squamous cell carcinoma of the head and neck (SCCHN), no reported studies have investigated the association between ADPRT and APE1 variants and SCCHN risk. In a hospital-based, case-control study of 830 non-Hispanic white patients with SCCHN and 854 cancer-free, matched control participants, the authors genotyped the ADPRT alanine 762 valine (Ala762Val) single-nucleotide polymorphism (SNP), the XRCC1 arginine 399 glutamine (Arg399Gln) SNP, and the APE aspartic acid 148 glutamic acid (Asp148Glu) SNP and assessed their associations with the risk of SCCHN in multivariate logistic regression models. The findings indicated that a significantly decreased risk of SCCHN was associated with the ADPRT 762Ala/Ala genotype (adjusted odds ratio [OR], 0.51; 95% confidence interval [95% CI], 0.27-0.97) and the combined ADPRT 762Ala/Val and Ala/Ala genotypes (OR, 0.79; 95% CI; 0.63-1.00) compared with the ADPRT 762Val/Val genotype, but no altered risk was associated with the XRCC1 Arg399Gln or APE Asp148Glu polymorphisms, and no evidence of interactions was observed between the 3 selected SNPs and age, sex, smoking status, drinking status, or tumor site. The ADPRT Ala762Val polymorphism may play a role in the etiology of SCCHN or in linkage disequilibrium with other untyped protective alleles. Larger studies with more SNPs in the BER genes will be needed to verify these findings.