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印度人群中12种赋予肺癌遗传风险的多态性变异的关联:一项广泛的荟萃分析。

Association of 12 polymorphic variants conferring genetic risk to lung cancer in Indian population: An extensive meta-analysis.

作者信息

Sengupta Debmalya, Guha Udayan, Bhattacharjee Samsiddhi, Sengupta Mainak

机构信息

Dept. of Genetics, University of Calcutta, Kolkata, India.

National Institute of Biomedical Genomics, Kalyani, India.

出版信息

Environ Mol Mutagen. 2017 Dec;58(9):688-700. doi: 10.1002/em.22149. Epub 2017 Oct 27.

Abstract

Candidate gene as well as genome-wide association studies identified several polymorphic variants to be associated with lung cancer worldwide including in India. However, contradictory results have failed to estimate the overall effect of the polymorphic variants on the disease. Textmining was conducted on PubMed following specific search strings to gather all the publications related to genetic association with lung cancer in India. Out of 211 PubMed hits only 30 studies were selected for meta-analysis following specific inclusion criteria. Heterogeneity between studies was calculated by Cochran's Q-test (P < 0.05) and heterogeneity index (I ). Publication bias was visualized by funnel plots and Egger's regression test. For each variant, following a fixed-effect model, summary odds ratio (OR) along with 95% confidence interval (CI) was estimated. The meta-analysis revealed three polymorphic variants viz. 'deletion polymorphism (del1) (OR = 1.39, 95% CI = 1.03-1.87, P = 0.027) in GSTT1', 'deletion polymorphism (del2) (OR = 1.30, 95% CI = 1.01-1.67, P = 0.038) in GSTM1' and 'rs1048943 (OR = 1.98, 95% CI = 1.27-3.10, P = 0.002) in CYP1A1' to be associated with lung cancer. However, after multiple testing correction, only rs1048943 was found to be significantly associated (P value = 0.0321) with lung cancer. None of the polymorphic variants showed any evidence of heterogeneity between studies or of publication bias. Our meta-analysis revealed strong association of rs1048943 in CYP1A1, but a suggestive association of deletion polymorphisms in GSTT1 and GSTM1 with lung cancer, which provides a comprehensive insight on the overall effect of the polymorphic variants, reported in various case-control studies on Indian population, on the risk of lung cancer development. Environ. Mol. Mutagen. 58:688-700, 2017. © 2017 Wiley Periodicals, Inc.

摘要

候选基因以及全基因组关联研究在全球范围内(包括印度)确定了几种与肺癌相关的多态性变体。然而,相互矛盾的结果未能评估这些多态性变体对该疾病的总体影响。按照特定的搜索词在PubMed上进行文本挖掘,以收集所有与印度肺癌遗传关联相关的出版物。在211条PubMed搜索结果中,仅根据特定的纳入标准选择了30项研究进行荟萃分析。通过 Cochr an Q检验(P < 0.05)和异质性指数(I²)计算研究之间的异质性。通过漏斗图和Egger回归检验直观显示发表偏倚。对于每个变体,采用固定效应模型估计汇总比值比(OR)以及95%置信区间(CI)。荟萃分析揭示了三种多态性变体,即谷胱甘肽S转移酶T1(GSTT1)中的“缺失多态性(del1)(OR = 1.39,95% CI = 1.03 - 1.87,P = 0.027)”、谷胱甘肽S转移酶M1(GSTM1)中的“缺失多态性(del2)(OR = 1.30,95% CI = 1.01 - 1.67,P = 0.038)”以及细胞色素P450 1A1(CYP1A1)中的“rs1048943(OR = 1.98,95% CI = 1.27 - 3.10,P = 0.002)”与肺癌相关。然而,经过多重检验校正后,仅发现rs1048943与肺癌显著相关(P值 = 0.0321)。没有一个多态性变体显示出研究之间存在异质性或发表偏倚的任何证据。我们的荟萃分析揭示了CYP1A1中rs1048943与肺癌有强关联,但GSTT1和GSTM1中的缺失多态性与肺癌有提示性关联,这为印度人群各种病例对照研究中报道的多态性变体对肺癌发生风险的总体影响提供了全面的见解。《环境与分子突变》58:688 - 700,2017年。© 2017威利期刊公司

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