These authors contributed equally to this work.
Polymorphism in xeroderma pigmentosum complementation group C codon 939 and aflatoxin B1–related hepatocellular carcinoma in the Guangxi population†
Article first published online: 16 JUN 2010
Copyright © 2010 American Association for the Study of Liver Diseases
Volume 52, Issue 4, pages 1301–1309, October 2010
How to Cite
Long, X.-D., Ma, Y., Zhou, Y.-F., Ma, A.-M. and Fu, G.-H. (2010), Polymorphism in xeroderma pigmentosum complementation group C codon 939 and aflatoxin B1–related hepatocellular carcinoma in the Guangxi population. Hepatology, 52: 1301–1309. doi: 10.1002/hep.23807
Potential conflict of interest: Nothing to report.
- Issue published online: 16 JUN 2010
- Article first published online: 16 JUN 2010
- Manuscript Accepted: 8 JUN 2010
- Manuscript Received: 14 APR 2010
- Youth Science Foundation of Guangxi. Grant Number: 0833097
- Science Foundation of Youjiang Medical College for Nationalities (2005 and 2008)
- National High Technology Research and Development Program of China through the 863 Program. Grant Number: 2008AA02Z120
Genetic polymorphisms in DNA repair genes may influence individual variations in DNA repair capacity, and this may be associated with the risk and outcome of hepatocellular carcinoma (HCC) related to aflatoxin B1 (AFB1) exposure. In this study, we focused on the polymorphism of xeroderma pigmentosum complementation group C (XPC) codon 939 (rs#2228001), which is involved in nucleotide excision repair. We conducted a case-control study including 1156 HCC cases and 1402 controls without any evidence of hepatic disease to evaluate the associations between this polymorphism and HCC risk and prognosis in the Guangxi population. AFB1 DNA adduct levels, XPC genotypes, and XPC protein levels were tested with a comparative enzyme-linked immunosorbent assay, TaqMan polymerase chain reaction for XPC genotypes, and immunohistochemistry, respectively. Higher AFB1 exposure was observed among HCC patients versus the control group [odds ratio (OR) = 9.88 for AFB1 exposure years and OR = 6.58 for AFB1 exposure levels]. The XPC codon 939 Gln alleles significantly increased HCC risk [OR = 1.25 (95% confidence interval = 1.03-1.52) for heterozygotes of the XPC codon 939 Lys and Gln alleles (XPC-LG) and OR = 1.81 (95% confidence interval = 1.36-2.40) for homozygotes of the XPC codon 939 Gln alleles (XPC-GG)]. Significant interactive effects between genotypes and AFB1 exposure status were also observed in the joint-effects analysis. This polymorphism, moreover, was correlated with XPC expression levels in cancerous tissues (r = −0.369, P < 0.001) and with the overall survival of HCC patients (the median survival times were 30, 25, and 19 months for patients with homozygotes of the XPC codon 939 Lys alleles, XPC-LG, and XPC-GG, respectively), especially under high AFB1 exposure conditions. Like AFB1 exposure, the XPC codon 939 polymorphism was an independent prognostic factor influencing the survival of HCC. Additionally, this polymorphism multiplicatively interacted with the xeroderma pigmentosum complementation group D codon 751 polymorphism with respect to HCC risk (ORinteraction = 1.71). Conclusion: These results suggest that the XPC codon 939 polymorphism may be associated with the risk and outcome of AFB1-related HCC in the Guangxi population and may interact with AFB1 exposure in the process of HCC induction by AFB1. (HEPATOLOGY 2010;)