Division of Infectious Disease Biology, Institute of Life Sciences, Bhubaneswar, India.
PLoS One. 2013 Oct 17;8(10):e77534. doi: 10.1371/journal.pone.0077534. eCollection 2013.
The Bcl-2-associated X protein (Bax) is a proapoptotic member of the Bcl-2 family known to be activated and upregulated during apoptosis. Single nucleotide polymorphisms (SNPs) in Bax promoter may participate in the process of carcinogenesis by altering its own expression and the cancer related genes. Bax-248G>A polymorphism has been implicated to alter the risk of cancer, but the listed results are inconsistent and inconclusive. In the present study, we performed a meta-analysis to systematically summarize the possible association of this polymorphism with the risk of cancer.
We conducted a search of case-control studies on the associations of Bax-248G>A polymorphism with susceptibility to cancer in Pub Med, Science Direct, Wiley Online Library and hand search. Data from all eligible studies based on some key search terms, inclusion and exclusion criteria were extracted for this meta-analysis. Hardy-Weinberg equilibrium (HWE) in controls, power calculation, heterogeneity analysis, Begg's funnel plot, Egger's linear regression test, forest plot and sensitivity analysis were performed in the present study.
Cancer risk associated with Bax-248G>A polymorphism was estimated by pooled odds ratios (ORs) and 95% confidence intervals (95% CIs). The pooled ORs were calculated in allele contrast, homozygous comparison, heterozygous comparison, dominant and recessive model. Statistical significance was checked through Z and p-value in forest plot. A total of seven independent studies including 1772 cases and 1708 controls were included in our meta-analysis. Our results showed that neither allele frequency nor genotype distributions of this polymorphism were associated with risk for cancer in any of the genetic model. Furthermore, Egger's test did not show any substantial evidence of publication bias.
CONCLUSIONS/SIGNIFICANCE: This meta-analysis suggests that the Bax-248G>A polymorphism is not an important cancer risk factor. Nevertheless, additional well-designed studies with larger sample size focusing on different ethnicities and cancer types are required to further validate the results.
Bcl-2 相关 X 蛋白（Bax）是 Bcl-2 家族的一种促凋亡成员，已知在细胞凋亡过程中被激活和上调。Bax 启动子中的单核苷酸多态性（SNP）可能通过改变自身表达和与癌症相关的基因参与致癌过程。Bax-248G>A 多态性与癌症风险的改变有关，但列出的结果不一致且没有定论。在本研究中，我们进行了一项荟萃分析，以系统总结这种多态性与癌症风险之间的可能关联。
我们在 Pub Med、Science Direct、Wiley Online Library 和手工搜索中搜索了 Bax-248G>A 多态性与癌症易感性相关的病例对照研究。根据一些关键搜索词、纳入和排除标准，从所有符合条件的研究中提取数据进行荟萃分析。本研究进行了 Hardy-Weinberg 平衡（HWE）检验、功效计算、异质性分析、Begg 漏斗图、Egger 线性回归检验、森林图和敏感性分析。
通过汇总优势比（ORs）和 95%置信区间（95%CI）来估计 Bax-248G>A 多态性与癌症风险的相关性。汇总 ORs 按等位基因对比、纯合子比较、杂合子比较、显性和隐性模型计算。森林图中的 Z 值和 p 值检查统计学意义。本荟萃分析共纳入了 7 项独立研究，包括 1772 例病例和 1708 例对照。我们的结果表明，在任何遗传模型中，该多态性的等位基因频率或基因型分布均与癌症风险无关。此外，Egger 检验未显示出任何实质性的发表偏倚证据。
结论/意义：这项荟萃分析表明，Bax-248G>A 多态性不是一个重要的癌症危险因素。然而，需要更多设计良好的、具有更大样本量、针对不同种族和癌症类型的研究来进一步验证结果。
