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分析大规模样本突出了 rs10411210 多态性与结直肠癌之间的显著关联。

Analyzing large-scale samples highlights significant association between rs10411210 polymorphism and colorectal cancer.

机构信息

Department of Intervention, The Affliated Tumor Hospital of Harbin Medical University, Harbin, Heilongjiang, China.

Comprehensive Internal Medicine Therapy Area, The Affliated Tumor Hospital of Harbin Medical University, Harbin, Heilongjiang, China.

出版信息

Biomed Pharmacother. 2015 Aug;74:164-8. doi: 10.1016/j.biopha.2015.08.023. Epub 2015 Aug 15.

Abstract

Colorectal cancer (CRC) is the third most common form of cancer and the second leading cause of cancer-related death in the Western countries. In order to detect common CRC genetic variants, genome-wide association studies (GWAS) have been performed and reported some novel CRC susceptibility variants. RHPN2 is located on 9q13.11, which encodes a member of the rhophilin family of Ras-homologous (Rho)-GTPase binding proteins. RHPN2 gene rs10411210 polymorphism was identified to be significantly associated with CRC in European ancestry. GWAS and candidate studies investigate whether rs10411210 polymorphism is associated with CRC risk in European, Asian and American populations. However, most studies reported no association. Evidence shows that RHPN2 rs10411210 variant may be a prognostic biomarker for patients with surgically resected CRC. Here we reevaluated this association using large-scale samples from 15 studies (131580 samples including 53564 CRC cases and 78016 controls) using meta-analysis method by searching the PubMed and Google Scholar databases. We did not identify significant heterogeneity among these 15 studies (P=0.4201 and I(2)=2.8%). Our results showed significant association between rs10411210 and CRC (P=9.17E-14, odds ratio (OR)=1.10, 95% confidence interval (CI) 1.07-1.13). In subgroup analysis, we found significant association between rs10411210 and CRC in European population with P=5.70E-09, OR=1.14, 95% CI 1.10-1.20 and Asian population with P=3.36E-07, OR=1.11, 95% CI 1.07-1.16, but not American population with P=0.0576, OR=1.05, 95% CI 1.00-1.09. Collectively, our analysis further highlights significant association between rs10411210 polymorphism and colorectal cancer.

摘要

结直肠癌(CRC)是西方国家第三大常见癌症,也是癌症相关死亡的第二大主要原因。为了检测常见的 CRC 遗传变异,已进行了全基因组关联研究(GWAS),并报道了一些新的 CRC 易感性变异。RHPN2 位于 9q13.11,编码 Ras-homologous(Rho)-GTPase 结合蛋白的 rhophilin 家族的一员。已鉴定 RHPN2 基因 rs10411210 多态性与欧洲血统的 CRC 显著相关。GWAS 和候选研究调查 rs10411210 多态性是否与欧洲、亚洲和美洲人群的 CRC 风险相关。然而,大多数研究报告没有关联。有证据表明,RHPN2 rs10411210 变体可能是接受手术切除的 CRC 患者的预后生物标志物。在这里,我们使用来自 15 项研究的大规模样本(包括 53564 例 CRC 病例和 78016 例对照),通过在 PubMed 和 Google Scholar 数据库中搜索,使用荟萃分析方法重新评估了这种关联。我们没有发现这 15 项研究之间存在显著的异质性(P=0.4201,I2=2.8%)。我们的结果表明,rs10411210 与 CRC 之间存在显著关联(P=9.17E-14,优势比(OR)=1.10,95%置信区间(CI)1.07-1.13)。在亚组分析中,我们发现 rs10411210 与欧洲人群中的 CRC 之间存在显著关联,P=5.70E-09,OR=1.14,95%CI 1.10-1.20,与亚洲人群中的 CRC 之间存在显著关联,P=3.36E-07,OR=1.11,95%CI 1.07-1.16,但与美洲人群中的 CRC 无显著关联,P=0.0576,OR=1.05,95%CI 1.00-1.09。总的来说,我们的分析进一步强调了 rs10411210 多态性与结直肠癌之间的显著关联。

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