UDP-glucuronosyltransferase 1A7 genetic polymorphisms are associated with hepatocellular carcinoma risk and onset age

• Published in: The American journal of gastroenterology Vol. 100; no. 8; pp. 1758 - 1763
• Main Authors: TSENG, Chien-Sen, TANG, Kung-Sheng, LO, Hoi-Wan, KER, Chen-Guo, TENG, Hsiu-Chen, HUANG, Ching-Shan
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell Publishing 01.08.2005; Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins
• Subjects: Adult; Age of Onset; Aged; Aged, 80 and over; Alleles; Biological and medical sciences; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - virology; Case-Control Studies; Female; Gastroenterology; Gastroenterology. Liver. Pancreas. Abdomen; Gene Frequency; Genetic Predisposition to Disease; Genotype; Glucuronosyltransferase - genetics; Humans; Liver Neoplasms - genetics; Liver Neoplasms - virology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Middle Aged; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Risk Factors; Taiwan; Tumors; Taiwan; UDP-glucuronosyltransferase; Enzyme; Transferases; Glycosyltransferases; Hepatic disease; Hepatocellular carcinoma; Malignant tumor; Risk factor; Digestive diseases; Genetics; Hexosyltransferases; Age; Polymorphism
• ISSN: 0002-9270; 1572-0241
• DOI: 10.1111/j.1572-0241.2005.41857.x

It has been demonstrated that the UDP-glucuronosyltransferase (UGT) 1A7*3 allele is a risk factor for hepatocellular carcinoma (HCC) in German and Japanese populations. In this study, therefore, we evaluated the association between UGT1A7 genetic polymorphisms and HCC risk in southern Taiwan, where hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are endemic. The 217 HCC patients and 291 controls enrolled in this case-control study were genotyped for UGT1A7 polymorphisms using polymerase chain reaction-restriction fragment length polymorphism. Univariate logistic regression analysis revealed that presence of UGT1A7*2 and *3 alleles was associated with HCC risk [odds ratio (OR) = 1.50, 95% confidence interval (CI): 1.04 approximately 2.16 and OR = 1.73, 95% CI: 1.19 approximately 2.52, respectively]. Multiple logistic regression analysis demonstrated that significant independent risk factors for HCC were male gender (OR = 2.53, 95% CI: 1.42 approximately 4.52), HBV infection (OR = 13.73, 95% CI: 8.04 approximately 23.46), HCV infection (OR = 83.93, 95% CI: 37.01 approximately 190.32), and low-activity UGT1A7 genotype [high/low (H/L) genotype: OR = 1.93, 95% CI: 1.12 approximately 3.32; low/low (L/L) genotype: OR = 3.06, 95% CI: 1.50 approximately 6.24]. For male HCC patients, significantly earlier onset age was observed for those bearing the UGT1A7 low-activity genotype as opposed to those with the high-activity analogue (median age: 50 vs 59 yr; p < 0.05). An inverse dose-response relationship was demonstrated between the detoxifying activity of the UGT1A7 genotypes and HCC. Of the male HCC patients, median onset age for those carrying an UGT1A7 low-activity genotype was 9 yr lower than those bearing the high-activity variant.