Lack of Association between the Functional Polymorphisms in the Estrogen-Metabolizing Genes and Risk for Hepatocellular Carcinoma
- Xiaoyan Yuan1,2,
- Gangqiao Zhou1,2,
- Yun Zhai1,2,
- Weimin Xie3,
- Ying Cui3,
- Jia Cao1,2,
- Lianteng Zhi1,2,
- Hongxing Zhang1,2,
- Hao Yang1,2,
- Xiaoai Zhang1,2,
- Wei Qiu1,2,
- Yong Peng3,
- Xiumei Zhang1,2,
- Ling Yu1,2,
- Xia Xia1,2 and
- Fuchu He1,2,4
- 1The State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China; 2Department of Hygienic Toxicology, Preventive Medical College, Third Military Medical University, Chongqing, China; 3Cancer Institute of Guangxi, Nanning, Guangxi, China; and 4Institute of Biomedical Sciences, Fudan University, Shanghai, China
- Requests for reprints:
Gangqiao Zhou and Fuchu He, The State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China. Phone/Fax: 86-10-80705255 or 86-10-68177417. E-mail: zhougq{at}chgb.org.cn and hefc{at}nic.bmi.ac.cn
Abstract
Estrogens have been proposed to act as tumor promoters and induce hepatocarcinogenesis. Recently, we observed a significant association between the risk for hepatocellular carcinoma and the polymorphisms of the estrogen receptor (ESR) α (ESR1) gene, supporting the hypothesis of involvement for the estrogen-ESR axis in the estrogen-induced hepatocarcinogenesis. In this study, based on another hypothesis in which estrogen metabolites can directly cause DNA damage and affect tumor initiation, we examined whether the polymorphisms of the estrogen-metabolizing enzymes (EME), which are involved in biogenesis (CYP17, CYP19), bioavailability (CYP1A1, CYP1B1), and degradation (catechol-O-methyltransferase) of the estrogens, have any bearing on the risk for hepatocellular carcinoma. Seven functional polymorphisms in five EMEs (CYP17 MspAI site, CYP19 Trp39Arg, Ile462Val and MspI site in CYP1A1, CYP1B1 Val432Leu, and Ala72Ser and Val158Met in catechol-O-methyltransferase) were genotyped in 434 patients with hepatocellular carcinoma and 480 controls by PCR-RFLP analysis. The associations between the polymorphisms and hepatocellular carcinoma risk were evaluated while controlling for confounding factors. No significant association with the risk for hepatocellular carcinoma was observed with the seven polymorphisms in hepatitis B virus carriers and non–hepatitis B virus carriers after correction for multiple comparisons. After stratification by common confounding factors of hepatocellular carcinoma, the EME polymorphism remained no significant association with the hepatocellular carcinoma risk. Furthermore, no signs of gene-gene interactions were observed for each combination of the seven polymorphisms. Our findings suggest that the polymorphisms of EMEs may not contribute significantly to the risk for hepatocellular carcinoma. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3621–7)
Footnotes
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Grant support: Chinese National Science Fund for Creative Research Groups Program grant 30621063 (F. He) and Chinese High-tech Program grant 2006AA02A412, Chinese National Basic Research Program grant 2006CB910803, Beijing Science & Technology NOVA Program grant 2006A54, and Chinese Key Project for the Infectious Diseases 2008ZX10002-016 (G. Zhou).
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- Accepted September 29, 2008.
- Received August 10, 2008.
- Revision received September 19, 2008.
