2A] and a higher dying risk (adjusted HR = 1.37 for XPC-LG and adjusted HR = 1.51 for XPC-GG; Table 5), particularly under high AFB1 exposure conditions (Fig. 2B,C). Furthermore, some evidence of multiplicative interaction was found for XPC genotypes Selleckchem Ku0059436 and AFB1 exposure years (Pinteraction = 0.012; Table 5). Because our previous study showed that the XPD codon 751 polymorphism, another DNA repair

gene involved in NER, modifies HCC risk in the Guangxi population,7 we explored possible interactions between XPC and XPD in 618 cases and 712 controls who had been previously studied.7 Because of the small number of subjects with both the homozygotes of the XPD codon 751 Gln alleles (XPD-GG) and XPC-GG, the combination

of these two genes was divided into four strata (Table 6). We found that individuals with both XPC-LG/GG and genotypes of the XPD codon 751 Gln alleles (XPD-LG/GG), in comparison with those with both XPC-LL and homozygotes of the XPD codon 751 Lys alleles (XPD-LL), might face a higher HCC risk (adjusted OR = 2.02, 95% CI = 1.42-2.87). A likelihood ratio test showed that there were multiplicatively interactive effects of XPC and XPD on the HCC risk (Pinteraction = 0.019). The most common cause of HCC is AFB1 exposure via the consumption of corn and groundnuts, which are Seliciclib primary food types for the Guangxi population, and HCC is one of the major cancer types in the Guangxi Zhuang Autonomous Region of China.1 Our previous studies5-7, 25, 27 and this study also show that HCC patients have more AFB1 exposure years and higher AFB1 exposure levels; moreover, we found that HCC risk is associated with different AFB1 exposure statuses. AFB1 is an important chemical carcinogen that is mainly metabolized by

cytochrome P450 into the genotoxic metabolic AFB1 epoxide; this selleck can bind to DNA, cause the formation of AFB1 guanine adducts, and induce DNA damage, including base damage and oxidative DNA damage that can be repaired by the NER pathway.2-4 XPC is an important DNA damage recognition molecule involved in the detection of a variety of DNA adducts formed by exogenous carcinogens such as AFB1.8-10 Some recent studies have shown that defects in XPC are related to many types of malignant tumors.21, 29 For example, Takebayashi et al.21 analyzed the loss of heterozygosity of XPC in sporadic ovarian, colon, and lung carcinomas. Their results showed that a deficiency of XPC results in the carcinogenesis of human tumors. Transgenic mouse studies have also revealed a predisposition to many types of tumors in XPC gene knockout mice.30 Our data also imply that a deficiency of XPC function promotes the carcinogenesis of HCC induced by AFB1 exposure. These results suggest that the XPC gene plays an important role in the prevention of DNA damage–mediated malignant tumor occurrence.