Background and purpose: Hepatocellular carcinoma (HCC) is a highly malignant tumour, and TNF-a may involve in the pathogenesis of HCC. The aim of this study was to explore the relationship of TNF-a gene -1031C/T (rs 1799964) and -308A/G (rs 1800629) 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-a-1031C/T and TNF-a-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 (P>0.05). They seemed not associated with HCC. Crossover analysis indicated that interactions existed between TNF-a-1031 and TNF-a-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 (0i?=19.822 for TNF-a-308). Conclusion: The single nucleotide polymorphisms (SNPs) onTNF-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.%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-a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-a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-a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.
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