Liu Fei, Luo Li-Mei, Wei Yong-Gang, Li Bo, Wang Wen-Tao, Wen Tian-Fu, Yang Jia-Yin, Xu Ming-Qing, Yan Lv-Nan
Department of Liver Surgery & Liver Transplantation Center, West China Hospital of Sichuan University, 37 Guo Xue Road, Chengdu 610041, Sichuan Province, China.
Department of Clinical Immunological Laboratory, West China Hospital of Sichuan University, 37 Guo Xue Road, Chengdu 610041, Sichuan Province, China.
Gene. 2015 Jun 10;564(1):14-20. doi: 10.1016/j.gene.2015.03.035. Epub 2015 Mar 18.
CYP1B1 is a P450 enzyme which is involved in the activation of pro-carcinogens to carcinogens as well as estrogen metabolism. We hypothesized that genetic variants in CYP1B1 may modify individual susceptibility to hepatocellular carcinoma (HCC).
To test this hypothesis, we evaluated the associations of three CYP1B1 single nucleotide polymorphisms (SNPs) and HCC risk in a case-control study of 468 HCC cases and 515 cancer-free controls in a Chinese population. The matrix-assisted laser desorption ionization time-of-flight mass spectrometry method and direct DNA sequencing were performed to detect these polymorphisms.
In overall analysis, we found that only the variant G allele of rs1056836 was associated with a significantly increased risk of HCC among the three SNPs (rs10012, rs1056836 and rs1800440). Moreover, we found that the variant genotypes containing the G allele of rs1056836 were associated with a significantly increased risk of HCC among HbsAg-positive individuals (adjusted OR=2.13, 95% CI=1.18, 3.86), but not among HbsAg-negative individuals. When stratifying by smoking status, we found that the variant GG genotype increased a 13.97-fold (95% CI=1.28, 152.94) risk of HCC among smokers. Furthermore, high risk for liver cirrhosis-positive clinical status was exhibited in HCC patients with rs1056836 CG and GG genotypes as compared with CC homozygotes. For the other two SNPs, we did not find any significant evidence of association with HCC risk in any subgroup.
This study suggests that CYP1B1 rs1056836 polymorphism may be an important factor contributing to increased susceptibility and pathological development of HCC in Chinese population.
细胞色素P450 1B1（CYP1B1）是一种P450酶，参与前致癌物向致癌物的激活以及雌激素代谢。我们推测CYP1B1基因变异可能会改变个体对肝细胞癌（HCC）的易感性。
为验证这一假设，我们在一项针对468例HCC病例和515例无癌对照的中国人群病例对照研究中，评估了三种CYP1B1单核苷酸多态性（SNP）与HCC风险的关联。采用基质辅助激光解吸电离飞行时间质谱法和直接DNA测序法检测这些多态性。
在总体分析中，我们发现，在三个SNP（rs10012、rs1056836和rs1800440）中，只有rs1056836的变异G等位基因与HCC风险显著增加相关。此外，我们发现，在乙肝表面抗原（HbsAg）阳性个体中，含有rs1056836的G等位基因的变异基因型与HCC风险显著增加相关（校正比值比=2.13，95%置信区间=1.18，3.86），而在HbsAg阴性个体中则不然。按吸烟状况分层时，我们发现，在吸烟者中，变异GG基因型使HCC风险增加了13.97倍（95%置信区间=1.28，152.94）。此外，与CC纯合子相比，rs1056836 CG和GG基因型的HCC患者表现出肝硬化阳性临床状态的高风险。对于其他两个SNP，我们在任何亚组中均未发现与HCC风险相关的任何显著证据。
本研究表明，CYP1B1 rs1056836多态性可能是导致中国人群HCC易感性增加和病理发展的一个重要因素。
