Ge Yu-Zheng, Wang Yi-Dan, Xu Zheng, Xu Lu-Wei, Wang Ya-Ping, Gu Mao-Hong, Ding Ai-Xing, Zhu Xian-Bo, Wu Ran, Li Wen-Cheng, Xu You-Di, Jia Rui-Peng
Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Tumour Biol. 2014 Jul;35(7):6405-14. doi: 10.1007/s13277-014-1861-9. Epub 2014 Mar 28.
Interferon gamma (IFN-γ) is a potent proinflammatory cytokine which plays a pivotal role in the antiviral, antiproliferative, and antitumor activities. A T-to-A transition at the position +874 of human IFN-γ gene (IFNG) has been reported to influence the secretion of IFN-γ and affect cancer susceptibility. However, results from published studies on the association between IFNG +874 T/A polymorphism and cancer risk are inconclusive or even controversial. In order to derive a more precise estimation of the association, a meta-analysis of 38 eligible studies including 5,630 cases and 6,096 controls was conducted with odds ratio (OR) and its corresponding 95 % confidence interval (95 % CI). Overall, no significant association was detected in allelic model (A allele vs. T allele-OR = 0.96, 95 % CI, 0.86-1.08), homozygote comparison (AA vs. TT-OR = 0.97, 95 % CI, 0.79-1.21), heterozygote comparison (AT vs. TT-OR = 1.03, 95 % CI, 0.87-1.23), dominant model (AA + AT vs. TT-OR = 1.00, 95 % CI, 0.87-1.15), nor recessive model (AA vs. AT + TT-OR = 0.93, 95 % CI, 0.78-1.12). Further subgroup analyses based on ethnicity, cancer types, and Hardy-Weinberg equilibrium status failed to demonstrate any significant relationship except in African population under recessive model (AA vs. AT + TT-OR = 0.68, 95 % CI, 0.47-0.97). In conclusion, the current meta-analysis suggested that IFNG +874 T/A polymorphism may not contribute to cancer susceptibility, and further well-designed studies with large sample size are warranted to validate our conclusion.
干扰素γ(IFN-γ)是一种强效促炎细胞因子,在抗病毒、抗增殖和抗肿瘤活性中起关键作用。据报道,人类IFN-γ基因(IFNG)+874位点的T到A转换会影响IFN-γ的分泌并影响癌症易感性。然而,已发表的关于IFNG +874 T/A多态性与癌症风险关联的研究结果尚无定论,甚至存在争议。为了更精确地估计这种关联,我们对38项符合条件的研究进行了荟萃分析,这些研究包括5630例病例和6096例对照,计算优势比(OR)及其相应的95%置信区间(95%CI)。总体而言,在等位基因模型(A等位基因与T等位基因,OR = 0.96,95%CI,0.86 - 1.08)中未检测到显著关联,纯合子比较(AA与TT,OR = 0.97,95%CI,0.79 - 1.21)、杂合子比较(AT与TT,OR = 1.03,95%CI,0.87 - 1.23)、显性模型(AA + AT与TT,OR = 1.00,95%CI,0.87 - 1.15)以及隐性模型(AA与AT + TT,OR = 0.93,95%CI,0.78 - 1.12)中均未检测到显著关联。基于种族、癌症类型和哈迪-温伯格平衡状态的进一步亚组分析未能证明任何显著关系,但在隐性模型下的非洲人群中除外(AA与AT + TT,OR = 0.68,95%CI,0.47 - 0.97)。总之,当前的荟萃分析表明,IFNG +874 T/A多态性可能与癌症易感性无关,需要进一步开展设计良好的大样本研究来验证我们的结论。