Zhenzhen Li, Xianghua Liu, Qingwei Wang, Zhan Guo, Ning Sun
The Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
Tumour Biol. 2013 Aug;34(4):2215-24. doi: 10.1007/s13277-013-0761-8. Epub 2013 Apr 10.
Interleukin-4 (IL-4) is a typical pleiotropic T helper 2 (Th2) cytokine. This cytokine is a critical mediator of the Th1/Th2 balance and apoptosis potential and involved in the process of inflammation-mediated carcinogenesis in human organs. IL-4 gene polymorphisms influence IL-4 transcription and have been implicated in cancer risks. However, current published data show conflicts among of them. To assess the relationship between IL-4 polymorphisms and cancer risks, we performed a meta-analysis which includes 14 studies involving 3,562 cancer cases for IL-4 rs2243250 polymorphism, 6 studies involving 2,052 subjects for IL-4 rs2070874 polymorphism, and 5 studies involving 791 subjects for IL-4 intron-3 polymorphism. As for rs2243250 polymorphism, no significant association of cancer risk was found in the overall analysis. When stratified by cancer type, we observed that the IL-4 rs2243250 polymorphism was significantly associated with decreased oral cancer risk and increased renal cell cancer risk (for oral cancer, TT vs. CC: odds ratio (OR) = 0.40, 95 % confidence interval (95 % CI) 0.19-0.84, P heterogeneity = 0.662, P = 0.016; TT/CT vs. CC: OR = 0.45, 95 % CI 0.22-0.94, P heterogeneity = 0.407, P = 0.033; and for renal cell cancer, TT vs. CC: OR = 1.98, 95 % CI 1.06-3.69, P heterogeneity = 0.535, P = 0.031; TT vs.
CC/CT: OR = 1.43, 95 % CI 1.05-1.95, P heterogeneity = 0.959, P = 0.022). For rs2070874 and intron-3 polymorphisms, no significant association of cancer risk was found in the overall analysis. However, in the subgroup analysis by source of controls and ethnicities, a significant association between cancer risk and rs2070874 polymorphism was found in population-based studies (A allele vs. G allele: OR = 1.18, 95 % CI 1.03-1.35, P heterogeneity = 0.621, P = 0.0172; AA vs.
AG/GG: OR = 1.23, 95 % CI 1.03-1.47, P heterogeneity = 0.196, P = 0.024) and Caucasian populations (A allele vs. G allele: OR = 1.24, 95 % CI 1.03-1.48, P heterogeneity = 0.925, P = 0.022), but not in Asian populations. Taken together, our results indicated that IL-4 rs2243250 polymorphism was associated with decreased oral cancer risk in both the homozygote contrasts and the dominant genetic model, as well as increased renal cell cancer risk in both the homozygote contrasts and the recessive genetic model. The A allele of rs2070874 polymorphism in the IL-4 gene may be a risk factor for cancer development among Caucasians. Further larger, preferably prospective studies are needed to confirm these results.
白细胞介素-4（IL-4）是一种典型的多效性辅助性T细胞2（Th2）细胞因子。这种细胞因子是Th1/Th2平衡和凋亡潜能的关键介质，参与人体器官炎症介导的致癌过程。IL-4基因多态性影响IL-4转录，并与癌症风险相关。然而，目前已发表的数据显示它们之间存在冲突。为了评估IL-4多态性与癌症风险之间的关系，我们进行了一项荟萃分析，其中包括14项涉及3562例癌症病例的关于IL-4 rs2243250多态性的研究、6项涉及2052名受试者的关于IL-4 rs2070874多态性的研究以及5项涉及791名受试者的关于IL-4内含子3多态性的研究。对于rs2243250多态性，在总体分析中未发现癌症风险的显著关联。当按癌症类型分层时，我们观察到IL-4 rs2243250多态性与口腔癌风险降低和肾细胞癌风险增加显著相关（对于口腔癌，TT与CC相比：比值比（OR）=0.40，95%置信区间（95%CI）0.19 - 0.84，P异质性 = 0.662，P = 0.016；TT/CT与CC相比：OR = 0.45，95%CI 0.22 - 0.94，P异质性 = 0.407，P = 0.033；对于肾细胞癌，TT与CC相比：OR = 1.98，95%CI 1.06 - 3.69，P异质性 = 0.535，P = 0.031；TT与CC/CT相比：OR = 1.43，95%CI 1.05 - 1.95，P异质性 = 0.959，P = 0.022）。对于rs2070874和内含子3多态性，在总体分析中未发现癌症风险的显著关联。然而，在按对照来源和种族进行的亚组分析中，在基于人群的研究（A等位基因与G等位基因相比：OR = 1.18，95%CI 1.03 - 1.35，P异质性 = 0.621，P = 0.0172；AA与AG/GG相比：OR = 1.23，95%CI 1.03 - 1.47，P异质性 = 0.196，P = 0.024）和白种人群体（A等位基因与G等位基因相比：OR = 1.24，95%CI 1.03 - 1.48，P异质性 = 0.925，P = 0.022）中发现癌症风险与rs2070874多态性之间存在显著关联，但在亚洲人群中未发现。综上所述，我们的结果表明，IL-4 rs2243250多态性在纯合子对比和显性遗传模型中均与口腔癌风险降低相关，在纯合子对比和隐性遗传模型中均与肾细胞癌风险增加相关。IL-4基因中rs2070874多态性的A等位基因可能是白种人癌症发生的一个风险因素。需要进一步开展更大规模、最好是前瞻性的研究来证实这些结果。
