The Polymorphism of XRCC3 Codon 241 and the Hotspot Mutation in the TP53 Gene in Hepatocellular Carcinoma Induced by Aflatoxin B1

Abstract

AIM: DNA repair gene X-ray repair cross-complementary group 3 (XRCC3) Thr241Met polymorphism (rs861539) is related to AFB1-DNA adducts and hepatocellular carcinoma (HCC). However, the association between this polymorphism and the hotspot mutation in codon 249 of TP53 gene (TP53M) is unclear. METHODS: A total of 585 HCCs were included in this study to investigate the role of the XRCC3 codon 241 polymorphism on TP53M risk. The genotypes of XRCC3 codon 241 and p53 codon 249 were examined by TaqMan-PCR technique. RESULTS: We found AFB1-DNA adduct levels were significantly correlated with increasing TP53M risk [adjusted odds ratio (OR)=3.30, 95% confidence interval (CI)=2.26-4.82]. The HCC patients with XRCC3 genotypes with 241 Met (namely: XRCC3-TM/MM) exhibited a significantly higher risk of TP53M than those with the wild-type homozygote of XRCC3 (namely: XRCC3-TT, OR=4.96, 95% CI=3.46-7.11). Compared with those individuals who did express XRCC3-MM as reference (OR=1), moreover, individuals featuring XRCC3-TM/MM and AFB1-DNA adducts did experience a significantly increasing risk of TP53M (OR=19.70, 95% CI=9.90-39.18, P<0.01). DISCUSSION: This study suggests that the XRCC3 Thr241Met polymorphism and AFB1-DNA adducts are associated with the increased TP53M risk.