Li Qiao-Yan, Zhao Ning-Min, Wang Lian-Cai, Duan Hong-Fei, Ma Yong-Cheng, Zhang Wei, Zhao Hong-Wei, Qin Yu-Hua
Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, No. 7, Weiwu Rd., Zhengzhou, 450003, Henan Province, China,
Tumour Biol. 2014 Sep;35(9):9023-6. doi: 10.1007/s13277-014-2144-1. Epub 2014 Jun 7.
Recently, many researchers have reported that the genetic polymorphisms of CYP2C19 may account for the interpatient variability of the clinical course in cancers including primary liver cancer (PLC). Besides the genetic polymorphisms of CYP2C19, hepatitis viruses (HV, including HAV, HBV, HCV, HDV, HEV, especially HBV and/or HCV) also account for the interpatient variability of the clinical course in PLC. This research covered the above two factors and divided the patients with PLC into two groups (one group with HBV infection and another without any HV infection) to find out whether the genetic polymorphisms of CYP2C19 have different effects in the progressing of PLC in different groups of patients. Eight hundred sixty-four cancer-free Han people (controls, named group 1), 207 Han PLC patients with HBV infection (group 2), and 55 Han PLC patients without any HV infection (group 3) were involved in this study. A wild-type allele (CYP2C191) and two mutated alleles (CYP2C192 and CYP2C19*3) were identified. The frequencies of the mutant alleles and genotypes were then compared with each other. The frequencies of the homozygous and heterozygous variant genotypes (*2/*2, *2/*3, *3/*3) in group 3 (25.5 %) were significantly higher than those in other groups (11.9 % in group 1 and 13.5 % in group 2, P = 0.014, 95 % confidence interval (CI)). The differences were statistically significant between group 1 and group 3 (P = 0.004, 95 % CI), but they were not statistically significant between group 1 and group 2 (P = 0.527, 95 % CI). Thus, we conclude that people which were not infected with HV but with the homozygous or heterozygous variant genotypes (*2/*2, *2/*3, *3/*3) of CYP2C19 may have higher possibilities of getting PLC than people with other allelic genotypes (*1/*1, *1/*2, *1/*3) (odds ratio (OR) = 2.523, 95 % CI = 1.329 ~ 4.788). However, in patients with HBV infection, the genetic polymorphisms of CYP2C19 did not seem to be an important factor in the risk of developing PLC (OR = 1.156, 95 % CI = 0.738 ~ 1.810).
最近，许多研究人员报告称，细胞色素P450 2C19（CYP2C19）的基因多态性可能是包括原发性肝癌（PLC）在内的癌症患者临床病程个体差异的原因。除了CYP2C19的基因多态性外，肝炎病毒（HV，包括甲型肝炎病毒、乙型肝炎病毒、丙型肝炎病毒、丁型肝炎病毒、戊型肝炎病毒，尤其是乙型肝炎病毒和/或丙型肝炎病毒）也是PLC患者临床病程个体差异的原因。本研究涵盖上述两个因素，将PLC患者分为两组（一组为乙型肝炎病毒感染患者，另一组为无任何肝炎病毒感染患者），以探究CYP2C19基因多态性在不同组PLC患者病程进展中的影响是否不同。本研究纳入了864名无癌汉族人（对照组，命名为第1组）、207名乙型肝炎病毒感染的汉族PLC患者（第2组）和55名无任何肝炎病毒感染的汉族PLC患者（第3组）。鉴定出一种野生型等位基因（CYP2C191）和两种突变等位基因（CYP2C192和CYP2C19*3）。然后比较突变等位基因和基因型的频率。第3组中纯合和杂合变异基因型（*2/*2、*2/*3、*3/*3）的频率（25.5%）显著高于其他组（第1组为11.9%，第2组为13.5%，P = 0.014，95%置信区间（CI））。第1组和第3组之间的差异具有统计学意义（P = 0.004，95% CI），但第1组和第2组之间的差异无统计学意义（P = 0.527，95% CI）。因此，我们得出结论，未感染肝炎病毒但具有CYP2C19纯合或杂合变异基因型（*2/*2、*2/*3、*3/*3）的人患PLC的可能性可能高于具有其他等位基因基因型（*1/*1、*1/*2、*1/*3）的人（优势比（OR）= 2.523，95% CI = 1.329至4.788）。然而，在乙型肝炎病毒感染患者中，CYP2C19基因多态性似乎不是发生PLC风险的重要因素（OR = 1.156，95% CI = 0.738至1.810）。
