Yuan Maoxi, Yu Chunmei, Yu Kuiying
Department of Thoracic Surgery, Linyi Central Hospital, No. 17 Jiankang Road, Yishui County, Linyi, Shandong 276400 People's Republic of China.
First Department of Neurology, The First Hospital of Zibo, Zibo, Shandong 255200 People's Republic of China.
Cancer Cell Int. 2020 May 13;20:164. doi: 10.1186/s12935-020-01244-5. eCollection 2020.
The objective of the present study is to comprehensively evaluate the impact of the rs1800975 A/G polymorphism within the human xeroderma pigmentosum group A () gene on susceptibility to overall cancer by performing an integrative analysis of the current evidence.
We retrieved possible relevant publications from a total of six electronic databases (updated to April 2020) and selected eligible case-control studies for pooled assessment. -values of association and odds ratio (OR) were calculated for the assessment of association effect. We also performed Begg's test and Egger's test, sensitivity analysis, false-positive report probability (FPRP) analysis, trial sequential analysis (TSA), and expression/splicing quantitative trait loci (eQTL/sQTL) analyses.
In total, 71 case-control studies with 19,257 cases and 30,208 controls from 52 publications were included for pooling analysis. We observed an enhanced overall cancer susceptibility in cancer cases compared with negative controls in the Caucasian subgroup analysis for the genetic models of allelic G vs. A, carrier G vs. A, homozygotic GG vs AA, heterozygotic AG vs. AA, dominant AG + GG vs. AA and recessive GG vs. AA + AG (< 0.05, OR > 1). A similar positive conclusion was also detected in the "skin cancer" or "skin basal cell carcinoma (BCC)" subgroup analysis of the Caucasian population. Our FPRP analysis and TSA results further confirmed the robustness of the conclusion. However, our eQTL/sQTL data did not support the strong links of rs1800975 with the gene expression or splicing changes of in the skin tissue. In addition, even though we observed a decreased risk of lung cancer under the homozygotic, heterozygotic and dominant models (< 0.05, OR < 1) and an enhanced risk of colorectal cancer under the allelic, homozygotic, heterozygotic, dominant (< 0.05, OR > 1), our data from FPRP analysis and another pooling analysis with only the population-based controls in the Caucasian population did not support the strong links between the rs1800975 A/G polymorphism and the risk of lung or colorectal cancer.
Our findings provide evidence of the close relationship between the rs1800975 A/G polymorphism and susceptibility to skin cancer in the Caucasian population. The potential effect of rs1800975 on the risk of developing lung or colorectal cancer still merits the enrollment of larger well-scaled studies.
本研究的目的是通过对现有证据进行综合分析，全面评估人类着色性干皮病A组（XPA）基因内rs1800975 A/G多态性对总体癌症易感性的影响。
我们从总共六个电子数据库（更新至2020年4月）中检索了可能相关的出版物，并选择符合条件的病例对照研究进行汇总评估。计算关联的P值和比值比（OR）以评估关联效应。我们还进行了Begg检验和Egger检验、敏感性分析、假阳性报告概率（FPRP）分析、试验序贯分析（TSA）以及表达/剪接数量性状位点（eQTL/sQTL）分析。
总共纳入了来自52篇出版物的71项病例对照研究，其中包括19257例病例和30208例对照进行汇总分析。在白种人亚组分析中，对于等位基因G与A、携带G与A、纯合子GG与AA、杂合子AG与AA、显性AG + GG与AA以及隐性GG与AA + AG的遗传模型，我们观察到癌症病例的总体癌症易感性相较于阴性对照有所增强（P < 0.05，OR > 1）。在白种人群体的“皮肤癌”或“皮肤基底细胞癌（BCC）”亚组分析中也检测到了类似的阳性结论。我们的FPRP分析和TSA结果进一步证实了该结论的稳健性。然而，我们的eQTL/sQTL数据不支持rs1800975与皮肤组织中XPA基因表达或剪接变化的紧密联系。此外，尽管我们在纯合子、杂合子和显性模型下观察到肺癌风险降低（P < 0.05，OR < 1），在等位基因、纯合子、杂合子、显性模型下观察到结直肠癌风险增加（P < 0.05，OR > 1），但我们的FPRP分析数据以及另一项仅对白种人群体中基于人群的对照进行的汇总分析数据均不支持rs1800975 A/G多态性与肺癌或结直肠癌风险之间的紧密联系。
我们的研究结果提供了证据，证明rs1800975 A/G多态性与白种人群体中皮肤癌易感性之间存在密切关系。rs1800975对肺癌或结直肠癌发生风险的潜在影响仍值得开展规模更大的充分研究。
