Han Cuihong, Huang Xiaoyi, Hua Ruixi, Song Shujie, Lyu Lihua, Ta Na, Zhu Jinhong, Zhang Peixi
Department of Pathology, Jining No. 1 People's Hospital, Jining, Shandong Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, Wenzhou, Zhejiang Molecular Epidemiology Laboratory, Department of Laboratory Medicine, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang Department of Cardio-Thoracic Surgery, Jining No. 1 People's Hospital, Jining, Shandong, China.
Medicine (Baltimore). 2017 Aug;96(32):e7467. doi: 10.1097/MD.0000000000007467.
Exposure to environmental carcinogens can cause damages to DNA. If not properly repaired, the DNA damages may increase the risk of carcinogenesis. Xeroderma pigmentosum group G (XPG) gene is an essential gene in the nucleotide excision repair (NER) pathway. The association between XPG polymorphisms and cancer susceptibility has been the focus of attention in the molecular epidemiology of cancer. However, the conclusions have been divergent. Therefore, we conducted a comprehensive meta-analysis to precisely evaluate the association of 3 frequently investigated XPG polymorphisms (rs751402, rs873601, and rs2296147) with cancer risk.
Pubmed, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) were searched for relevant studies in English and Chinese. Odds ratio (OR) and 95% confidence interval (CI) were used to assess the association between XPG polymorphisms (rs751402, rs873601, and rs2296147) and cancer risk.
Twenty-three studies were included. Overall, there was no significant association between rs751402 polymorphism and overall cancer risk under the 5 gene models. However, we observed strong correlation between rs751402 polymorphism and gastric cancer (C vs T: OR=1.21, 95% CI = 1.00-1.26, P = .045; TC vs CC: OR = 1.12, 95% CI = 1.00-1.24, P = .041; TC/TT vs CC: OR = 1.13, 95% CI = 1.02-1.26, P = .020). There was a significant correlation between rs873601 polymorphism and cancer risk under the homozygous model (GG vs AA: OR = 1.16, 95% CI = 1.07-1.26, P = .001). Moreover, significant association with breast cancer was detected for rs873601 polymorphism under the allele contrast model (G vs A: OR = 1.10, 95% CI = 1.02-1.20, P = .021). In the subgroup of Asian, rs873601 polymorphism was related to the susceptibility to cancer (G vs A: OR = 1.07, 95% CI = 1.03-1.12, P = .010; GG vs AA: OR = 1.15, 95% CI = 1.06-1.26, P = .001; AG/AA vs GG: OR = 1.08, 95% CI = 1.01-1.15, P = .031; AA vs AG/GG: OR = 1.13, 95% CI = 1.05-1.21, P = .001). Significant association between rs2296147 polymorphism and cancer risk were observed in Asian population (CT vs TT: OR = 0.93, 95% CI = 0.87-0.99, P = .036).
Our meta-analysis suggested that the rs873601 polymorphism was significantly associated with overall cancer risk. The moderate effects of rs751402 and rs2296147 polymorphism on cancer susceptibility might be highly dependent on cancer type and ethnicity, respectively. Large studies are needed to validate our findings, especially in Caucasian and African population.
暴露于环境致癌物会导致DNA损伤。若未得到妥善修复，DNA损伤可能会增加致癌风险。G组着色性干皮病（XPG）基因是核苷酸切除修复（NER）途径中的一个关键基因。XPG基因多态性与癌症易感性之间的关联一直是癌症分子流行病学关注的焦点。然而，结论却存在分歧。因此，我们进行了一项全面的荟萃分析，以精确评估3个经常研究的XPG基因多态性（rs751402、rs873601和rs2296147）与癌症风险的关联。
检索了PubMed、EMBASE和中国知网（CNKI）上的中英文相关研究。采用比值比（OR）和95%置信区间（CI）来评估XPG基因多态性（rs751402、rs873601和rs2296147）与癌症风险之间的关联。
纳入了23项研究。总体而言，在5种基因模型下，rs751402基因多态性与总体癌症风险之间无显著关联。然而，我们观察到rs751402基因多态性与胃癌之间存在强相关性（C vs T：OR=1.21，95%CI=1.00-1.26，P=0.045；TC vs CC：OR=1.12，95%CI=1.00-1.24，P=0.041；TC/TT vs CC：OR=1.13，95%CI=1.02-1.26，P=0.020）。在纯合子模型下，rs873601基因多态性与癌症风险之间存在显著相关性（GG vs AA：OR=1.16，95%CI=1.07-1.26，P=0.001）。此外，在等位基因对比模型下，检测到rs873601基因多态性与乳腺癌之间存在显著关联（G vs A：OR=1.10，95%CI=1.02-1.20，P=0.021）。在亚洲人群亚组中，rs873601基因多态性与癌症易感性相关（G vs A：OR=1.07，95%CI=1.03-1.12，P=0.010；GG vs AA：OR=1.15，95%CI=1.06-1.26，P=0.001；AG/AA vs GG：OR=1.08，95%CI=1.01-1.15，P=0.031；AA vs AG/GG：OR=1.13，95%CI=1.05-1.21，P=0.001）。在亚洲人群中观察到rs2296147基因多态性与癌症风险之间存在显著关联（CT vs TT：OR=0.93，95%CI=0.87-0.99，P=0.036）。
我们的荟萃分析表明，rs873601基因多态性与总体癌症风险显著相关。rs751402和rs2296147基因多态性对癌症易感性的中等影响可能分别高度依赖于癌症类型和种族。需要开展大规模研究来验证我们的发现，尤其是在白种人和非洲人群中。
