title: Polymorphisms of estrogen-metabolizing genes and risk of hepatocellular carcinoma in Taiwan females.
abstract: Estrogen has been related to the development of hepatocellular carcinoma (HCC). In this molecular epidemiological study, we used logistic regression to compare the genotype frequencies of estrogen-metabolizing genes that are involved in estrogen biogenesis (CYP17), hydroxylation (CYP1A1) and inactivation of the reactive metabolites (catechol-O-methyltransferase, COMT) in HCC patients and control subjects, and determined their relationship with the risk of female HCC. The heterozygous or homozygous variants of high activity CYP17 (A2), high inducibility CYP1A1(m1), and low activity COMT (L) alleles were considered as high-risk genotypes. We found that the risk of HCC was elevated in women harboring either heterozygous or homozygous variants of the CYP1A1 gene and the respective OR (and 95% confidence interval) were 6.61 (1.35, 32.43) and 12.00 (1.73, 83.46). Moreover, we found that the risk of HCC was increased in the female subjects harboring higher numbers of high-risk genotypes, but not in male subjects. The OR for female HCC associated with two putative high-risk genotypes was 12.63 (1.50, 106.37), and the OR for three putative high-risk genotypes was 16.67 (1.82, 152.77). These findings strongly suggest that estrogen play a critical role in female hepatocarcinogenesis.
authors.affiliation: Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Pen-Hui
authors.initials: PH
authors.lastname: Yin
authors.forename: Hsin-Chen
authors.initials: HC
authors.lastname: Lee
authors.forename: Gar-Yang
authors.initials: GY
authors.lastname: Chau
authors.forename: Tsung-Yun
authors.initials: TY
authors.lastname: Liu
authors.forename: Hsiu-Chih
authors.initials: HC
authors.lastname: Liu
authors.forename: Wing-Yiu
authors.initials: WY
authors.lastname: Lui
authors.forename: Chin-Wen
authors.initials: CW
authors.lastname: Chi
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D002394:Catechol O-Methyltransferase / Q000235:genetics; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D004247:DNA / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011960:Receptors, Estrogen / Q000235:genetics*; D012306:Risk; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics; D013624:Taiwan
chemical_list: D004967:Estrogens; D011960:Receptors, Estrogen; D004247:DNA; D019363:Cytochrome P-450 CYP1A1; D013254:Steroid 17-alpha-Hydroxylase; D002394:Catechol O-Methyltransferase