核苷酸切除修复途径基因多态性与胃癌及萎缩性胃炎风险的关联。
Association of nucleotide excision repair pathway gene polymorphisms with gastric cancer and atrophic gastritis risks.
作者信息
Liu Jingwei, Sun Liping, Xu Qian, Tu Huakang, He Caiyun, Xing Chengzhong, Yuan Yuan
机构信息
Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, China.
Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Provincial Education Department, Shenyang 110001, China.
出版信息
Oncotarget. 2016 Feb 9;7(6):6972-83. doi: 10.18632/oncotarget.6853.
Polymorphisms of NER genes could change NER ability, thereby altering individual susceptibility to GC. We systematically analyzed 39 SNPs of 8 key genes of NER pathway in 2686 subjects including 898 gastric cancer (GC), 851 atrophic gastritis (AG) and 937 controls (CON) in northern Chinese. SNP genotyping were performed using Sequenom MassARRAY platform. The results demonstrated that DDB2 rs830083 GG genotype was significantly associated with increased GC risk compared with wild-type CC (OR=2.32, P= 6.62 × 10-9); XPC rs2607775 CG genotype conferred a 1.73 increased odds of GC risk than non-cancer subjects compared with wild-type CC (OR=1.73, P= 3.04 × 10-4). The combined detection of these two polymorphisms demonstrated even higher GC risk (OR=3.05). Haplotype analysis suggested that DDB2 rs2029298-rs326222-rs3781619-rs830083 GTAG haplotype was significantly associated with disease risk in each step of CON→AG→GC development (AG vs. CON: OR=2.88, P= 7.51 × 10-7; GC vs. AG: OR=2.90, P=5.68 × 10-15; GC vs. CON: OR=8.42, P=2.22 × 10-15); DDB2 GTAC haplotype was associated with reduced risk of GC compared with CON (OR=0.63, P= 8.31 × 10-12). XPC rs1870134-rs2228000-rs2228001-rs2470352-rs2607775 GCAAG haplotype conferred increased risk of GC compared with AG (OR=1.88, P= 6.98 × 10-4). XPA rs2808668 and drinking, DDB2 rs326222, rs3781619, rs830083 and smoking demonstrated significant interactions in AG; XPC rs2607775 had significant interaction with smoking in GC. In conclusion, NER pathway polymorphisms especially in "damage incision" step were significantly associated with GC risk and had interactions with environment factors. The detection of NER pathway polymorphisms such as DDB2 and XPC might be applied in the prediction of GC risk and personalized prevention in the future. NER pathway polymorphisms especially in "damage incision" step were significantly associated with GC risk and had interactions with environment factors, which might be applied in the prediction of GC risk and personalized prevention in the future.
核苷酸切除修复（NER）基因的多态性可能会改变NER能力，从而改变个体对胃癌（GC）的易感性。我们在中国北方的2686名受试者中系统分析了NER途径8个关键基因的39个单核苷酸多态性（SNP），其中包括898例胃癌（GC）患者、851例萎缩性胃炎（AG）患者和937例对照（CON）。使用Sequenom MassARRAY平台进行SNP基因分型。结果表明，与野生型CC相比，DDB2 rs830083 GG基因型与GC风险增加显著相关（比值比[OR]=2.32，P=6.62×10⁻⁹）；与野生型CC相比，XPC rs2607775 CG基因型使GC风险比非癌症受试者增加了1.73倍（OR=1.73，P=3.04×10⁻⁴）。这两种多态性的联合检测显示GC风险更高（OR=3.05）。单倍型分析表明，DDB2 rs2029298 - rs326222 - rs3781619 - rs830083 GTAG单倍型在CON→AG→GC发展的每个阶段都与疾病风险显著相关（AG与CON相比：OR=2.88，P=7.51×10⁻⁷；GC与AG相比：OR=2.90，P=5.68×10⁻¹⁵；GC与CON相比：OR=8.42，P=2.22×10⁻¹⁵）；与CON相比，DDB2 GTAC单倍型与GC风险降低相关（OR=0.63，P=8.31×10⁻¹²）。XPC rs1870134 - rs2228000 - rs2228001 - rs2470352 - rs2607775 GCAAG单倍型与AG相比，GC风险增加（OR=1.88，P=6.98×10⁻⁴）。XPA rs2808668与饮酒、DDB2 rs326222、rs3781619、rs830083与吸烟在AG中有显著交互作用；XPC rs2607775与吸烟在GC中有显著交互作用。总之，NER途径多态性尤其是在“损伤切割”步骤中与GC风险显著相关，并与环境因素存在交互作用。检测DDB2和XPC等NER途径多态性可能在未来用于GC风险预测和个性化预防。NER途径多态性尤其是在“损伤切割”步骤中与GC风险显著相关，并与环境因素存在交互作用，这可能在未来用于GC风险预测和个性化预防。
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