Genome integrity is maintained by an intricate network of DNA repair proteins [33, 34]. Organisms have developed several DNA-repair pathways as well as DNA-damage checkpoints. Defects in this complex machinery are associated with genotoxic susceptibility and familial predispositions VEGFR inhibitor to cancer [35]. Increasing evidence links environmental exposures, subtle modification in DNA repair efficiency, and cancer risk [36]. XRCC1 participates in DNA single strand break and base excision repair to protect genome stability in mammalian cells. One of the common polymorphisms of XRCC1

the Arg399Gln is located in the BRCT1 domain responsible for interacting with other repair components of BER. It was reported that Arg→Gln substitution produces significant conformational changes at BRCT1 domain that may be critical for DNA repair protein-protein interactions [37], thus absence or impairment repair

may cause genome instability and cancer occurrence. It is also important to Buparlisib integrate DNA-repair process with DNA-damage checkpoints and cell survival, to evaluate the role of DNA repair at both cellular and organismic levels. Therefore, protective effects of XRCC1 polymorphisms in cancer may also be observed by the enhanced efficiency of apoptosis at a cellular level as a result of diminished DNA repair capacity secondary to the genetic polymorphisms [38, Branched chain aminotransferase 39]. In our study, neither of these SNPs was found to individually contribute to head and neck cancer risk. There were no differences between the distribution of the genotypes or alleles frequences in patients and controls. However, we found statistically non-significant increase of Arg194Trp genotype frequency (OR, 1.37; 95% CI, 0.70–2.68) and Trp194 allele (OR, 1.32; 95% CI, 0.70–2.49) according to wild-type of Arg194Arg

reference genotype and Arg194 allele frequency (table 2). Non-statistical increase of Arg399Gln (OR, 1.10; 95% CI, 0.61–1.97) according to reference genotype of Arg399Arg was also found. (table 3). While, no altered risk has been found individually for the XRCC1 Arg194Trp or Arg399Gln polymorphisms, the halophyte analysis according to wild-type of Arg194Arg-Arg399Arg showed high association with head and neck cancer (table 4). The findings indicated that a statistically non-significantly increased risk of HNSCC was associated with the combined Arg194Arg-Arg399Gln genotype (OR, 1.33; 95% CI, 0.70–2.56). The higher risk of head and neck cancer occurrence was associated with the combined Arg194Trp-Arg399Arg genotype (OR, 2.96; 95% CI, 1.01–8.80) but no altered risk was associated with others haplotypes. For Tyr165Tyr genotype we also observed positive correlation with cancer progression assessed by tumor size (OR 4.56; 95% CI 1.60–12.95).