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Polymorphism in xeroderma pigmentosum complementation group C codon 939 and aflatoxin B1–related hepatocellular carcinoma in the Guangxi population
Author(s) -
Long XiDai,
Ma Yun,
Zhou YuanFeng,
Ma AiMin,
Fu GuoHui
Publication year - 2010
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.23807
Subject(s) - xeroderma pigmentosum , hepatocellular carcinoma , genotype , odds ratio , biology , allele , population , dna repair , genetics , nucleotide excision repair , gastroenterology , cancer research , medicine , oncology , microbiology and biotechnology , gene , environmental health
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 (OR interaction = 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. (H EPATOLOGY 2010;)