title: Common genetic variations of the cytochrome P450 1A1 gene and risk of hepatocellular carcinoma in a Chinese population.
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.
authors.affiliation: 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.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
authors.forename: Yin Yao
authors.initials: YY
authors.lastname: Shugart
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, PR China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: Yu
authors.initials: Y
authors.lastname: An
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, PR China; International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Shanghai, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Shanghai, PR China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Shanghai, PR China.
authors.forename: Beibei
authors.initials: B
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Daru
authors.initials: D
authors.lastname: Lu
authors.affiliation: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Shanghai, PR China. Electronic address: hywangk@vip.sina.com.
authors.forename: Hongyang
authors.initials: H
authors.lastname: Wang
authors.affiliation: 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. Electronic address: jiqian@fudan.edu.cn.
authors.forename: Ji
authors.initials: J
authors.lastname: Qian
authors.affiliation: 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.
authors.forename: Li
authors.initials: L
authors.lastname: Jin
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics*; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012306:Risk; D012907:Smoking
chemical_list: D019363:Cytochrome P-450 CYP1A1