背景与目的:原发性肝细胞癌(hepatocellular carcinoma,HCC)是一种高度恶性的肿瘤,TNF-α参与了HCC的病理发生、发展过程。本研究探讨广西地区人群TNF-α基因启动子区-1031C/T(rs1799964)和-308A/G(rs1800629)的单核苷酸多态性及其与环境因素的交互作用与HCC遗传易感性的关系。方法:采用以医院为基础的病例对照研究,选择来自于广西地区的新发HCC患者620例,相同地区年龄、性别和民族频数匹配的非肿瘤患者625例。采用TaqMan MGB实时荧光定量PCR方法对TNF-α基因-1031位点和-308位点进行基因分型,比较不同基因型与HCC患病风险的关系,并探讨基因-环境的交互作用对患病风险的影响。结果:TNF-a基因-1031位点3种基因型TT、TC、CC在病例组和对照组中分布差异无统计学意义(P〉0.05),与TT基因型患者相比,TC或CC基因型者患HCC的风险并无显著增加(P〉0.05)。TNF-α基因-308位点GG、GA、AA基因型在病例组和对照组中分布差异无统计学意义(P〉0.05),与GG基因型患者相比,GA或AA基因型者患HCC的风险并无显著增加(P〉0.05)。叉生分析结果表明,TNF-α基因-1031位点单核苷酸多态性与吸烟、饮酒及HBV感染等环境因素在HCC发生中存在交互作用,OR分别为3.367、4.709和25.433;-308位点与吸烟、饮酒、食鱼生及HBV感染等环境因素在HCC发生中存在交互作用,OR分别为3.720、5.316、24.975和19.822。结论:TNF-α基因-1031位点和-308位点单核苷酸多态性在HCC发生过程中,可能无独立的危险作用,但与吸烟、饮酒、食鱼生及HBsAg阳性等环境因素交互作用能增加HCC的发病风险。
Background and purpose:Hepatocellular carcinoma(HCC) is a highly malignant tumour,and TNF-α may involve in the pathogenesis of HCC.The aim of this study was to explore the relationship of TNF-α gene-1031C/T(rs1799964) and-308A/G(rs1800629) polymorphisms and gene-environment interaction with the susceptibility to HCC.Methods:A hospital-based case-control study was conducted in 620 cases with HCC and 625 controls matched for age,gender,ethnicity and residence.Genotypes of TNF-α-1031C/T and TNF-α-308A/G were determined by real-time polymerase chain reaction with the TaqMan MGB probe.Results:For the genotypes of-1031 and-308 site,there were no significant differences between cases and controls(P0.05).They seemed not associated with HCC.Crossover analysis indicated that interactions existed between TNF-α-1031 and TNF-α-308 polymorphisms with environment risk factors such as tobacco smoking history(OR=3.367,OR=3.720,respectively),alcohol drinking history(OR=4.709,OR=5.316,respectively),hepatitis B virus infection(OR=25.433,OR=24.975,respectively),raw fish consumption history(OR=19.822 for TNF-α-308).Conclusion:The single nucleotide polymorphisms(SNPs) on TNF-a promoter at-1031 and-308 sites do not increase the risk of HCC by themselves,but increase the risk of HCC together with environmental factors including smoking,drinking,consumption of pieces of raw fish and hepatitis B virus infection in Guangxi population.