Clinical and Experimental Pharmacology, CRO-National Cancer Institute, Aviano, PN, Italy.
Unit of Cancer Epidemiology, CRO-National Cancer Institute, Aviano, PN, Italy.
Liver Int. 2017 Sep;37(9):1345-1353. doi: 10.1111/liv.13411. Epub 2017 Apr 6.
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.
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.
UGT1A73 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). UGT1A128 (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.
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.
肝细胞癌（HCC）风险的新型生物标志物的定义，特别是在高危 HBV/HCV 阳性人群中，迫切需要提高 HCC 的临床管理水平。本研究集中于 UDP-葡糖醛酸基转移酶 1A（UGT1A）酶的变体，这些变体催化葡糖醛酸化反应，这是身体最重要的化学防御途径之一。本研究的目的是阐明 UGT1A 多态性在预测高加索人群 HCC 易感性中的作用。
在这项回顾性病例对照分析中，192 名 HCC 肝移植患者代表研究组。使用两个年龄/性别匹配的组作为对照，一组由 167 名 HBV 和/或 HCV 感染个体组成，另一组由 192 名健康受试者组成。所有病例均进行了 UGT1A1、UGT1A7 和 UGT1A9 变体的检测。研究终点是 UGT1A 标志物与 HCC 发病之间的关联。
UGT1A73 等位基因是高危 HBV/HCV 阳性患者（OR=0.64，P=.0026）和健康受试者（OR=0.47，P=.0051）中 HCC 发展的保护标志物。UGT1A128（OR=0.61，P=.0013）和 UGT1A9*22（OR=2.18，P=.0003）等位基因也与 HCC 发生有关，尤其是在健康受试者中。总结 UGT1A 遗传改变的 UGT1A 单倍型证实了低活性等位基因对 HCC 发展的保护作用。观察到的关联可能与有益健康的分子（包括游离胆红素）血清水平的增加有关。
UGT1A 多态性对 HCC 风险具有预测作用。如果得到证实，这些发现可能有助于提高 HCC 监测、治疗个体化和患者护理水平。
