佛山顺德区居民IL6及IL10单核苷酸多态性与原发性肝癌遗传易感性的关联分析

The association between single-nucleotide polymorphisms in IL6,IL10 genes and the susceptibility to primary hepatic carcinoma in Shunde District of Foshan City

目的 分析广东顺德地区居民IL6及IL10单核苷酸多态性与原发性肝癌遗传易感性的关联.方法 选择2010年10月至2012年10月就诊于佛山顺德区两家医院患者.病例组纳入标准：原发性肝癌;顺德本地居民或在顺德当地居住10年及以上.对照组纳入标准：与病例组患者同期在同院于耳鼻喉科、普外科和体检科就诊的病例;顺德本地居民或在顺德当地居住10年及以上;依据病例组患者的性别、诊断时年龄（±3岁）进行1：1匹配.共收集病例和对照组对象各306例.采用问卷对患者进行调查,内容包括：人口学特征、原发性肝癌状况调查等.并采集静脉血后提取DNA,选择SNP位点并检测基因型.采用拟合优度χ2检验验证对照组人群基因型分布是否存在Hardy-Weinberg平衡;采用多因素条件logistic回归模型分析rs1800796、rs1800871和rs1800872位点基因多态性与原发性肝癌遗传易感性的关系.结果 病例组和对照组的男性均为264例,女性均为42例,年龄分别为（55.84±11.49）和（55.83±11.67）岁.对照组的IL6（rs1800796）、IL10（rs1800871）和IL10（rs1800872）基因型频率符合Hardy-Weinberg平衡（P值均〉0.05）,即研究人群具有代表性.调整吸烟史,进食鱼生史,饮酒史,慢性乙肝感染和肝癌家族史等因素后,与携带IL10（rs1800872）位点AA基因型相比,携带CC基因型的个体患肝癌的风险增加2.02倍（OR=3.02,95%CI：1.21~7.56）;与携带AA＋AC基因型相比,携带CC基因型的个体罹患肝癌风险增加1.89倍（OR=2.89,95%CI：1.19~7.04）.IL6（rs1800796）单核苷酸多态性与原发性肝癌遗传易感性的关联无统计学意义（P〉0.05）.结论 携带IL10（rs1800872）CC基因型个体罹患原发性肝癌风险增加.

Objective To investigate the association between single nucleotide polymorphisms （SNP） in cytokine IL6, IL10 genes and the susceptibility to primary hepatic carcinoma（PHC） of Shunde district in Guangdong Province. Methods Patients from two hospitals in Shunde District of Foshan City were selected from October 2010 to October 2012. Case group inclusion criteria includedprimary liver cancer; local residents of Shunde or living in Shunde for more than 10 years. The control group inclusion criteria included： patients visited ENT, general surgery and physical examination department in the same hospital during the same period; Local residents or living in Shunde for 10 years and above. The control group was matched 1：1 by gender, and age （±3 years old） with case group. A total of 306 subjects were collected. Questionnaires were used to investigate the information including demographic characteristics, PHC status survey and so on. The venous blood was collected from each subject to extract DNA, and to detect label SNP site and genotype. Hardy-Weinberg equilibrium was detected in the control group by the goodness-of-fit χ2 test. Multivariate conditional logistic regression was used to estimate the relationship between IL6 （rs1800796）, IL10 （rs1800871, rs1800872）genes polymorphisms and susceptibility to PHC. Results There were 264 males and 42 females both in the case group and the control group, with an average age of （55.84±11.49） and （55.83±11.67） years old respectively （t=0.011, P=0.992）. The frequencies of IL6 （rs1800796）, IL10 （rs1800871） and IL10 （rs1800872） genotypes in the control group were in accordance with the Hardy-Weinberg equilibrium, which indicated the population was representative （all P values〉0.05）. Conditional logistic regression analysis showed that compared with the AA genotype and AA＋AC genotype of IL10（rs1800872） ,CC genotype increased the risk of PHC by 2.02 times （OR=3.02, 95%CI：1.21-7.56）and 1.89 times （OR=2.89,95%CI：1.19-7.04）respectively after the smoking history, eating fish history, drinking history, chronic hepatitis B infection, and family history of liver cancer adjusted. No statistical association was found between SNP in cytokine IL6 （rs1800796） and the susceptibility to PHC （P〉0.05）. Conclusion The results indicated that people who carried CC genotype in rs1800872 of IL10 gene have an increasing risk of PHC.