Polymorphisms of estrogen-metabolizing genes and risk of hepatocellular carcinoma in Taiwan females.
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.
Yin
Pen-Hui
PH
Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Lee
Hsin-Chen
HC
Chau
Gar-Yang
GY
Liu
Tsung-Yun
TY
Liu
Hsiu-Chih
HC
Lui
Wing-Yiu
WY
Chi
Chin-Wen
CW
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
D004967:Estrogens; D011960:Receptors, Estrogen; D004247:DNA; D019363:Cytochrome P-450 CYP1A1; D013254:Steroid 17-alpha-Hydroxylase; D002394:Catechol O-Methyltransferase