Borentain Patrick, Gérolami Victoria, Ananian Pascal, Garcia Stéphane, Noundou Anderson, Botta-Fridlund Daniele, Le Treut Yves Patrice, Bergé-Lefranc Jean Louis, Gérolami René
Service d'hépatogastroentérologie, CHU Conception, 147 Bd Baille, 13005 Marseille, France.
Eur J Cancer. 2007 Nov;43(17):2479-86. doi: 10.1016/j.ejca.2007.08.006. Epub 2007 Sep 17.
We studied polymorphisms of three genes, UDP-glucuronosyltransferase1A7 (UGT1A7), Glutathione-S-transferaseM1 (GSTM1) and X-Ray Cross Complementing group 1 (XRCC1), involved in detoxification of xenobiotics or DNA-repair in a population of 133 liver-transplanted patients, including 56 patients with hepatocellular carcinoma (HCC) and 77 without HCC, and in 89 healthy controls originating from the south of France. Multiple logistic regression analysis showed that, among liver-transplanted patients, interactions between XRCC1-G/G or -G/A and GSTM1-nul polymorphisms were independently associated with hepatocellular carcinoma (p interaction=0.027) concurrently with increasing age (p<0.001), male sex (p=0.037) and chronic hepatitis B or C virus infection (p=0.018 and p=0.001 respectively). On the contrary, no relationship was observed between UGT1A7 polymorphisms considered alone or in interaction with GSTM1 or XRCC1 polymorphisms and HCC. This suggests that concomitant impaired metabolism of carcinogenic compounds and impaired DNA-repair function play an important role in liver carcinogenesis in high-risk cirrhotic patients originating from the south of France.
我们研究了参与外源性物质解毒或DNA修复的三个基因，即尿苷二磷酸葡萄糖醛酸基转移酶1A7（UGT1A7）、谷胱甘肽 - S - 转移酶M1（GSTM1）和X射线交叉互补组1（XRCC1）的多态性，研究对象为133例肝移植患者，其中包括56例肝细胞癌（HCC）患者和77例无HCC患者，以及89名来自法国南部的健康对照者。多因素逻辑回归分析表明，在肝移植患者中，XRCC1 - G/G或 - G/A与GSTM1 - 无效多态性之间的相互作用与肝细胞癌独立相关（p相互作用 = 0.027），同时年龄增加（p < 0.001）、男性（p = 0.037）以及慢性乙型或丙型肝炎病毒感染（分别为p = 0.018和p = 0.001）也与之相关。相反，单独考虑UGT1A7多态性或其与GSTM1或XRCC1多态性的相互作用与HCC之间未观察到相关性。这表明致癌化合物代谢受损和DNA修复功能受损同时存在，在来自法国南部的高危肝硬化患者的肝癌发生中起重要作用。
