Polymorphism Of The DNA Repair Gene XRCC1 And Risk Of Aflatoxin B₁-related Hepatocellular Carcinoma

Backgrounds and Aims: Hepatocellular carcinoma (HCC) is a very common cancer that causes serious damage to human health. Aflatoxin B, (AFB1 as a chemical carcinogen that produces much DNA damage including DNA-base-damage (DBD) and single-strand break (SSB), has been well documented as a major etiologic factor of HCC. XRCC1 (x-ray repair cross-complementing group 1) is a base excision repair protein that plays a central role in the repair of DNA base damage and single-strand break, because it serves as a scaffold for the two repair proteins, DNA ligase III and DNA polymerase bata , and also serves as a single-strand break sensor by its interaction with poly(ADP-ribose)polymerase (PARP). There are three codingpolymorphisms in the XRCC1 gene at the exon 6, codon 194 C→T, Arg →Trp; exon 9, codon 280G→A, Arg→His; and exon 10, codon 399, G → A, Arg→Gln. In particular, the codon 399 Gln polymorphism resulting from a guanine to adenine nucleotide transition occurs in the PARP and PNK binding domain and may affect complex assembly or repair efficiency. To determine whether the XRCC1 codon 399 Gln allele is a risk factor for HCC in Guangxi population, we have examinated the role of XRCC1 as a candidate susceptible gene for HCC.Methods: The hospital-base case-control study population consist of 140 cases (HCC) and 536 controls from the First Affiliated Hospital for Guangxi Medical University. Controls were frequently matched to cases on sex, age and race. PCR-RFLP was used to detect the polymorphism of the peripheral blood white blood cells DNA obtained from all the subjects.Results:1. The distribution of XRCC1 399 codon polymorphism is not significantly different between Southwest Guangxi population from high AFBl-exposure area and the other Guangxi population from low/median AFBl-exposure area (x2=1.651, P=0.438);2. The XRCC1 coden 399 Arg/Arg is associated with decreasing HCC risk;3. The XRCC1 codon 399 (Gln/Gln+Arg/Gln) is associated with increasing HCC risk (adjusted OR=2.18, 95%CI=1. 27-3.74);4. In the cohort of having low/median level of AFBi exposure, the codon 399 Gln allele is great significance which increase in risk of HCC (adjustd OR=2. 06, 95%CI=1. 01-4. 19).Conclusion: The XRCC1 codon 399 polymorphism is associated withthe risk of HCC. There is evidence for interaction between XRCC1 codon 399 Gln allele and AFB1 exposure, especially with low/median degrees of AFB1 exposure.