The TNF-Alpha-238 Polymorphism and Cancer Risk: A Meta-Analysis

Background and ObjectivesTumor necrosis factor-α (TNF-α) plays a very important role in the development and progress of cancer. Some TNF-α polymorphisms have been confirmed to increase cancer risks; however, the association between TNF-α-238 polymorphism and cancers remains controversial and ambiguous. The aim of this study is to explore a more precise estimation of its relationship with cancer using meta-analysis. MethodsElectronic searches of several databases were conducted for all publications on the association between this variant and cancer through March 2011. Odds ratios (OR) with 95% confidence intervals (95% CI) were used to access the strength of this association in the random-effect model. ResultsThirty four studies with 34,679 cancer patients and 41,186 healthy controls were included. This meta-analysis showed no significant association between TNF-α-238 polymorphism and cancers (AA+GA vs GG: OR = 1.09, 95%CI = 0.88–1.34). In Caucasian and Asian subgroups, OR values (95% CI) were 1.14 (0.91–1.43) and 0.97 (0.58–1.61), respectively. In the subgroups of cancer type, no significant association was detected. The sensitivity analysis further strengthened the validity of these negative associations. No publication bias was observed in this study. ConclusionsNo significant association was found between the TNF-α-238 polymorphism and the risk for cancer.

背景与目的 肿瘤坏死因子-α（Tumor necrosis factor-α, TNF-α）在癌症的发生与进展过程中发挥着至关重要的作用。目前已有多项肿瘤坏死因子-α基因多态性被证实可增加癌症发病风险，但肿瘤坏死因子-α-238（TNF-α-238）基因多态性与癌症的关联仍存在争议且尚不明确。本研究旨在通过荟萃分析（meta-analysis）更精准地评估该多态性与癌症的关联。
方法 本研究对多个数据库进行电子检索，截至2011年3月，纳入所有关于该位点多态性与癌症关联的已发表文献。采用随机效应模型（random-effect model），以比值比（Odds ratio, OR）及95%置信区间（95% confidence interval, 95%CI）评估该关联的强度。
结果 本研究共纳入34项研究，涉及34679名癌症患者与41186名健康对照。本次荟萃分析结果显示，肿瘤坏死因子-α-238基因多态性与癌症风险无显著关联（AA+GA vs GG：OR=1.09，95%CI=0.88–1.34）。在高加索人群与亚洲人群亚组中，对应的OR值（95%CI）分别为1.14（0.91–1.43）与0.97（0.58–1.61）。在癌症类型亚组分析中，同样未检测到显著关联。敏感性分析（sensitivity analysis）进一步验证了上述阴性关联的可靠性。本研究未观察到发表偏倚（publication bias）。
结论 肿瘤坏死因子-α-238基因多态性与癌症发病风险无显著关联。