Functional polymorphism rs4072037 in MUC1 gene contributes to the susceptibility to gastric cancer: evidence from pooled 6,580 cases and 10,324 controls
Functional polymorphism rs4072037 in MUC1 gene contributes to the susceptibility to gastric cancer: evidence from pooled 6,580 cases and 10,324 controls
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DOI：
10.1007/s11033-013-2682-4
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发表时间：
2013-10-01
影响因子：
2.8
通讯作者：
Jin, Guangfu
中科院分区：
文献类型：
--
作者：
Zheng, Leizhen;Zhu, Chen;Jin, Guangfu
全基因组关联研究已经报道了rs 4072037与胃癌（GC）的有希望的关联。这种变异可能通过调节MUC 1的启动子活性和选择性剪接与MUC 1的生理功能改变相关。然而，相关性结果是不确定的，对这种变异的影响的估计没有得到很好的评价。通过系统地审查相关报告进行的荟萃分析可能有助于解决这些问题。截至2012年6月30日，确定了涉及MUC 1 rs 4072037多态性和GC风险的关联研究。从每项研究中估计或提取相加模型中的比值比（OR）和95%置信区间（CI）。使用荟萃分析对合并效应量进行定量合成。通过Q检验和I（2）统计量测量研究间的异质性，通过漏斗图和Egger检验评估发表偏倚。本荟萃分析共纳入10项独立病例对照研究，包括6，580例GC病例和10，324例对照。十项研究中有八项是亚洲种族，两项是欧洲种族。与A等位基因相比，MUC 1 rs 4072037的G等位基因与GC风险降低显著相关（OR = 0.72，95%CI 0.68-0.77; P = 7.82 x 10（-25））。不同种族、肿瘤位置或类型的分层显示了相似的结果。这些发现代表了MUC 1 rs 4072037变异与GC风险相关的重要证据，也提供了相对可靠的效应大小估计。MUC 1是胃癌易感基因的候选基因。
Genome-wide association studies have reported a promising association of rs4072037 with gastric cancer (GC). This variant was associated with altered physiological function of MUC1 possibly by modulating promoter activity and alternative splicing of MUC1. However, the association results were inconclusive and estimate of the effect of this variant was not well evaluated. A meta-analysis by systematically reviewing relevant reports may facilitate to address these concerns. Association studies involving MUC1 rs4072037 polymorphism and GC risk were identified up to June 30, 2012. Odds ratio (OR) and 95 % confidence interval (CI) in additive model were estimated or extracted from each study. The pooled effect size was quantitatively synthesized using meta-analysis. Heterogeneity between studies was measured by the Q test and I (2) statistic, and publication bias was evaluated by a funnel plot and the Egger's test. A total of 10 independent case-control studies including 6,580 GC cases and 10,324 controls were included in this meta-analysis. Eight of the ten studies were Asian ethnicity and two European. The G allele of MUC1 rs4072037 was significantly associated with a decreased risk of GC (OR = 0.72, 95 % CI 0.68-0.77; P = 7.82 x 10(-25)), as compared with A allele. Stratification for different ethnicity, tumor localization or type showed similar results. These findings represent important evidence for association of MUC1 rs4072037 variant with GC risk, and also provide a relatively reliable estimate of effect size. MUC1 is a strong candidate as a susceptibility gene of GC.