UGT1A polymorphisms as genetic biomarkers for hepatocellular carcinoma risk in Caucasian population

Background & Aims: The definition of new biomarkers of hepatocellular carcinoma (HCC) risk, especially in high-risk HBV/HCV-positive population, is urgently needed to improve HCC clinical management. This study focused on variants of UDP-glucuronosyltransferase 1A (UGT1A) enzymes that catalyse the reaction of glucuronidation, one of the most important chemical defence pathway of the body. The aim of this study was to elucidate the contribution of UGT1A polymorphisms in predicting HCC susceptibility in Caucasians. Methods: In this retrospective case-control analysis, 192 HCC liver transplanted patients represent the study group. Two age/sex-matched groups were used as control, one composed of 167 HBV- and/or HCV-infected individuals, and the other of 192 healthy subjects. All the cases were characterized for a panel of UGT1A1, UGT1A7 and UGT1A9 variants. The study end-point was the association between UGT1A markers and HCC onset. Results: UGT1A7*3 allele emerged as a protective marker for HCC development among both high-risk HBV/HCV-positive patients (OR=0.64, P=.0026), and healthy subjects (OR=0.47, P=.0051). UGT1A1*28 (OR=0.61, P=.0013) and UGT1A9*22 (OR=2.18, P=.0003) alleles were also associated to HCC occurrence, especially among healthy subjects. UGT1A haplotype, summarizing the UGT1A genetic alterations, confirmed the protective role against HCC development emerged for low-activity alleles. The observed associations could probably be linked to an increase of serum levels of health-beneficial molecules including free bilirubin. Conclusion: A predictive effect of UGT1A polymorphisms on HCC risk was identified. If confirmed, these findings could contribute to improve the HCC surveillance, treatment tailoring and patients care.