Genetic link of hepatocellular carcinoma with polymorphisms of the UDP-glucuronosyltransferase UGT1A7 gene

Gastroenterology. 2001 Nov;121(5):1136-44. doi: 10.1053/gast.2001.28655.


Background & aims: Hepatocellular carcinoma is associated with risk factors including hepatitis C, hepatitis B, cirrhosis, genetic liver diseases, and environmental carcinogens. Uridine 5'-diphosphate-glucuronosyltransferases are a superfamily of detoxifying enzymes capable of tobacco-borne carcinogen detoxification and cellular protection. This study examines the association of UGT1A7 and UGT1A9 gene polymorphisms with hepatocellular carcinoma.

Methods: Genomic DNA from the blood of 59 patients with hepatocellular carcinoma and 70 control subjects without evidence of cancer was analyzed by UGT1A7- and UGT1A9-specific PCR, sequencing analysis, and temperature gradient gel electrophoresis.

Results: Three UGT1A7 missense mutations were detected defining the UGT1A7*2, UGT1A7*3, and UGT1A7*4 alleles. Wild-type UGT1A7 alleles were present in 41.4% of controls but only in 6.8% of cancer patients (P < 0.001; odds ratio [OR], 9.73; 95% confidence interval [CI], 3.17-29.83). UGT1A7 polymorphisms were present in 93.2% of hepatocellular cancer patients, 74.5% carried the UGT1A7*3 allele (P < 0.001; OR, 10.76; 95% CI, 4.75-24.38), which combines the W208R, N129K, and R131K mutations and encodes a protein with low carcinogen detoxification activity. No UGT1A9 polymorphisms were detected.

Conclusions: The significant association of hepatocellular carcinoma with the UGT1A7*3 allele encoding a low detoxification activity protein is identified and implicates UGT1A7 as a risk gene of hepatocarcinogenesis in addition to a role as potential marker for cancer risk assessment in chronic liver disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Hepatocellular / enzymology
  • Carcinoma, Hepatocellular / genetics*
  • Exons
  • Female
  • Glucuronosyltransferase / genetics*
  • Humans
  • Liver Neoplasms / enzymology
  • Liver Neoplasms / genetics*
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*


  • Glucuronosyltransferase