UGT1A7 haplotype is associated with an increased risk of hepatocellular carcinoma in hepatitis B carriers

The UGT1A7 gene encodes UDP-glucuronosyltransferase, a key enzyme catalyzing the glucuronidation of various carcinogens. In this study, we investigated the association between haplotypes of the whole UGT1A7 gene and the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B. Sequence analysis of exon1 and the promoter region of the UGT1A7 gene was carried out to determine haplotype profiles for 244 patients with hepatocellular carcinoma, 223 hepatitis B carriers, and 314 healthy control subjects. Hepatitis B carriers with haplotypes other than haplotype 1 (Ht1; CTCTCGTG at –341, –57, 33, 387, 391, 392, 622, and 756) had a significantly greater risk of developing HCC with odds ratios (OR) of 1.67 (95% confidence interval [CI]; 1.11–2.52) for Ht1/others and 1.85 (95% CI; 1.09–3.14) for others/others. In multivariate logistic regression analysis including age and haplotypes from Ht1 to Ht4, the presence of Ht2 (CGAGAACG) or Ht4 (CTCGAATG) was associated with HCC risk (OR = 1.45 [95% CI; 1.03–2.03] and 4.95 [95% CI; 1.75–13.98], respectively). The results of this study show that the UGT1A7 haplotype is a suitable susceptibility marker for the development of HCC in hepatitis B carriers. ( Cancer Sci 2008; 99: 340–344)