The Polymorphism of XRCC3 Codon 241 and AFB1-Related Hepatocellular Carcinoma in Guangxi Population, China
Purpose
The relationship between aflatoxin B1 (AFB1) exposure and hepatocellular carcinoma (HCC) has been previously demonstrated and supported with strong epidemiological evidence. However, the role of genetic polymorphism of X-ray cross-complementing group 3 (XRCC3) codon 241 (namely: Thr241Met), which may be involved in the repair of DNA double-strand breaks caused by carcinogens such as AFB1, been less well elaborated.
Methods
We conducted a case–control study including 491 cases and 862 controls to evaluate the associations between this polymorphism and HCC risk for Guangxi population by means of polymerase chain reaction-restriction fragment length polymorphism analysis.
Results
We found that individuals with the XRCC3 genotypes with codon 241 Met (namely XRCC3-TM or XRCC3-MM) had an increased risk of HCC than those with the homozygote of XRCC3 codon 241 Thr alleles (namely XRCC3-TT, adjusted odds ratios 2.22 and 7.19; 95% confidence intervals 1.72–2.88 and 4.52–11.42, respectively). The risk of HCC, moreover, did appear to differ more significantly among individuals featuring high-level AFB1-DNA adducts, whose adjusted odds ratios (95% confidence intervals) were 11.59 (5.73–23.47) and 37.54 (16.32–86.32), respectively.
Conclusions
These findings support the hypothesis that the XRCC3 Thr241Met polymorphism may be associated with the risk of AFB1-related HCC among the Guangxi population.
Key Words: HCC, XRCC3, Polymorphism, AFB1
Selected Abbreviations and Acronyms: HCC, hepatocellular carcinoma, AFB1, aflatoxin B1, SSB, single-strand breaks, DSB, double-strand breaks, HRR, homologous recombination repair, XRCC3, X-ray repair cross-complementing group 3, XRCC3-MM, the homozygotes of XRCC3 codon 241 Met alleles, XRCC3-TM, the heterozygotes of XRCC3 codon 241 Met and Thy allele, XRCC3-TM/MM, the XRCC3 genotypes with codon 241 Met alleles, XRCC3-TT, the homozygote of XRCC3 codon 241Thr alleles, HBV, hepatic B virus, HCV, hepatic C virus, HBsAg, hepatitis B surface antigen, PCR, polymerase chain reaction, RFLP, restriction fragment length polymorphism, 95% CI, confidence interval, OR, odds ratio
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Drs. Long and Ma contributed equally to this work.
This study is supported by the Science Foundation of Youjiang Medical College for Nationalities (NO. 2005 and 2008) and the National Nature & Science Foundation of China (NO. 39860032).
PII: S1047-2797(08)00058-6
doi:10.1016/j.annepidem.2008.03.003
© 2008 Elsevier Inc. All rights reserved.
