Common genetic variations of the cytochrome P450 1A1 gene and risk of hepatocellular carcinoma in a Chinese population |
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| Authors: | Rui Li Yin Yao Shugart Weiping Zhou Yu An Yuan Yang Yun Zhou Beibei Zhang Daru Lu Hongyang Wang Ji Qian Li Jin |
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| Affiliation: | 1. State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, 220 Handan Rd., Shanghai 200433, PR China;2. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States;3. Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States;4. The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, PR China;5. International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Shanghai, PR China;1. Department of Hepatic Surgery III, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, PR China;2. Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region;3. National Innovation Alliance for Hepatitis & Liver Cancer, Shanghai, PR China;1. Institution of Medical Management and Policy Research, College of Public Policy and Management, Xi''an Jiao Tong University, Xi''an, China;2. Department of Radiotherapy Oncology, The First Affiliated Hospital of Medical College of Xi''an Jiao Tong University, Xi''an, China;3. Department of Pediatrics Baoji Central Hospital of Shaanxi Province, Baoji, China;2. National Center of Occupational Safety and Health, Beijing 102308, China;4. Wugang Institute for Occupational Health, Wugang 462500, Henan, China |
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| Abstract: | Cytochrome P450 1A1 is a major enzyme in the bioactivation of exogenous procarcinogens of hepatocellular carcinoma (HCC). However, the contribution of common genetic variants in CYP1A1 to the HCC risk in Chinese populations has not been thoroughly investigated. In this study, we examined the association between HCC and four selected tagging single nucleotide polymorphisms (SNPs) of CYP1A1, and the risk of CYP1A1 haplotypes/diplotypes in 1006 pathologically confirmed HCC patients and 1015 cancer-free controls, from a Han Chinese population. Haplotypes/diplotypes were constructed from observed genotypes using the Haplo.Stats program. Relative risk was estimated by using multivariable logistic regression method. To summarise, we detected an increased HCC risk in rs4646421 variant carriers (OR 1.30, 95% CI 1.05–1.61) and rs2198843 variant carriers (OR 1.33, 95% CI 1.05-1.69), and a reduced risk of HCC (OR 0.70. 95% CI 0.52–0.94) associated with homozygote carriers of rs4886605 variant. These association signals were also observed in non-smokers with rs4646421 (OR 1.56, 95% CI 1.16–2.08) and rs4886605 (OR 0.61, 95% CI 0.40–0.91). Compared to the most common CYP1A1 haplotype CCAG, the haplotype TTGC conferred an increased risk of HCC (OR 1.26, 95% CI 1.04–1.52). Similarly, the TTGC/TTGC diplotype conferred an increased risk of HCC compared with diplotype CCAG/CCAG (OR 2.06, 95% CI 1.23–3.45, P = 0.006). Interestingly, the diplotype TTAC/CCAG also conferred an increased risk of HCC (OR 1.76, 95% CI 1.22–2.54, P = 0.003). Our results suggested that common genetic variants in CYP1A1 may modulate the risk of developing HCC in the study population, particularly in non-smokers. However, our findings need to be validated in at least one independent study of Han Chinese population. |
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