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CYP1A1基因A2455G多态性与癌症风险的关联:来自272项病例对照研究的证据。

Association between the CYP1A1 A2455G polymorphism and risk of cancer: evidence from 272 case-control studies.

作者信息

Qin Jun, Zhang Jin-Xia, Li Xiao-Ping, Wu Bu-Qiang, Chen Guang-Bin, He Xiao-Feng

机构信息

Department of General Surgery, Peace Hospital of Changzhi Medical College, Changzhi, 046000, China.

出版信息

Tumour Biol. 2014 Apr;35(4):3363-76. doi: 10.1007/s13277-013-1443-2. Epub 2013 Dec 5.

Abstract

A2455G is a common polymorphism in CYP1A1, showing differences in its biological functions. Case-control studies have been performed to elucidate the role of A2455G in cancer; however, the results are conflicting and heterogeneous. Hence, we performed a meta-analysis to investigate the association between cancer susceptibility and A2455G (64,593 cases and 91,056 controls from 272 studies) polymorphism in different inheritance models. We used odds ratios with 95% confidence intervals to assess the strength of the association. Overall, significantly increased cancer risk was observed in any genetic model (dominant model, odds ration [OR] = 1.19, 95% confidence interval [CI] = 1.13-1.25; recessive model: OR = 1.41, 95% CI = 1.29-1.54; additive model: OR = 1.49, 95% CI = 1.35-1.65) when all eligible studies were pooled into the meta-analysis. In further stratified and sensitivity analyses, the elevated risk remained for subgroups of breast cancer, colorectal cancer, esophageal cancer, hepatocellular cancer, head and neck cancer, leukemia, lung cancer, and prostate cancer, but these associations vary in different ethnic populations. In summary, this meta-analysis suggests the participation of A2455G in the susceptibility for some cancers, such as breast cancer, colorectal cancer, lung cancer, and so on. Moreover, ethnicity, histological type of cancer, and smokers seem to contribute to varying expressions of the A2455G on some cancers risk. In addition, our work also points out the importance of new studies for A2455G polymorphism in some cancer types, such as gallbladder cancer, Indians of breast cancer, and Caucasians of ovarians, because these cancer types had high heterogeneity in this meta-analysis (I(2) > 75%).

摘要

A2455G是CYP1A1基因中一种常见的多态性,其生物学功能存在差异。已有病例对照研究来阐明A2455G在癌症中的作用;然而,结果相互矛盾且存在异质性。因此,我们进行了一项荟萃分析,以研究不同遗传模型中癌症易感性与A2455G(来自272项研究的64593例病例和91056例对照)多态性之间的关联。我们使用比值比及95%置信区间来评估关联强度。总体而言,当所有符合条件的研究纳入荟萃分析时,在任何遗传模型中均观察到癌症风险显著增加(显性模型:比值比[OR]=1.19,95%置信区间[CI]=1.13 - 1.25;隐性模型:OR = 1.41,95% CI = 1.29 - 1.54;加性模型:OR = 1.49,95% CI = 1.35 - 1.65)。在进一步的分层和敏感性分析中,乳腺癌、结直肠癌、食管癌、肝细胞癌、头颈癌、白血病、肺癌和前列腺癌亚组的风险仍然升高,但这些关联在不同种族人群中有所不同。总之,这项荟萃分析表明A2455G参与了某些癌症的易感性,如乳腺癌、结直肠癌、肺癌等。此外,种族、癌症组织学类型和吸烟者似乎导致A2455G对某些癌症风险的表达存在差异。此外,我们的研究还指出了针对某些癌症类型(如胆囊癌、印度裔乳腺癌和高加索裔卵巢癌)的A2455G多态性进行新研究的重要性,因为这些癌症类型在本次荟萃分析中具有高度异质性(I²>75%)。

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