| 刘亚倩,汪天培,颜财旺,朱猛,杨明,王梦筠,胡志斌,沈洪兵,靳光付.多基因遗传风险评分与胃癌发病年龄的关联分析[J].Chinese journal of Epidemiology,2021,42(6):1092-1096 |
| 多基因遗传风险评分与胃癌发病年龄的关联分析 |
| Association between polygenic risk score and age at onset of gastric cancer |
| Received:November 03, 2020 |
| DOI：10.3760/cma.j.cn112338-20201103-01303 |
| KeyWord: 肿瘤,胃 早发 全基因组关联研究 多基因风险评分 |
| English Key Word: Gastric neoplasm Early-onset Genome-wide association study Polygenic risk score |
| FundProject:国家重点研发计划（2016YFC1302700）；国家自然科学基金（81872702） |
| Author Name | Affiliation | E-mail | | Liu Yaqian | Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing 211166, China | | | Wang Tianpei | Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing 211166, China | | | Yan Caiwang | Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing 211166, China | | | Zhu Meng | Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing 211166, China | | | Yang Ming | Basic Research Center, Shandong Provincial Cancer Research Institute, Ji'nan 250117, China | | | Wang Mengyun | Fudan University Shanghai Cancer Center, Shanghai 200032, China | | | Hu Zhibin | Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing 211166, China | | | Shen Hongbing | Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing 211166, China | | | Jin Guangfu | Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing 211166, China | guangfujin@njmu.edu.cn |
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| Abstract: |
| 目的 探讨多基因遗传风险评分（PRS）与胃癌发病年龄及早发风险之间的关系。方法 基于胃癌全基因组关联研究，以胃癌病例为研究对象，利用112个与胃癌发生风险有关的单核苷酸多态性位点构建PRS，采用方差分析和Pearson相关性检验分析PRS水平与胃癌发病年龄的关系。将发病年龄<50岁的病例定义为早发胃癌病例，以低遗传风险（PRS≤20%）为参照组，采用Cox比例风险模型以早发诊断年龄为时间变量分析中遗传风险（PRS：20%~80%）和高遗传风险（PRS>80%）与胃癌早发风险的关联。结果 共纳入8 629例胃癌病例，其中，男性6 284例（72.82%），女性2 345例（27.18%），发病年龄为（60.61±10.80）岁。PRS水平与胃癌发病年龄呈显著负相关（r=-0.05，P<0.001），PRS越高胃癌发病年龄越小，低、中、高遗传风险组胃癌发病年龄分别为（61.68±10.33）岁、（60.53±10.79）岁、（59.80±11.20）岁。PRS与胃癌早发风险呈剂量反应关系（中遗传风险：HR=1.19，95%CI：1.03~1.39，P=0.022；高遗传风险：HR=1.44，95%CI：1.20~1.71，P<0.001）。结论 高PRS不仅增加胃癌发病风险，同时也是胃癌早发的危险因素，PRS可作为遗传检测指标评估胃癌发病和早发风险。 |
| English Abstract: |
| Objective To explore the association between polygenic risk score (PRS) and age at onset and early-onset risk of gastric cancer (GC). Methods Gastric cancer cases from existing genome-wide association study were included, and 112 single nucleotide polymorphisms associated with GC risk were used to derive individual PRS. Analysis of variance and Pearson correlation test was used to depict the relationship between PRS and GC onset age. Cases diagnosed before 50 years old were defined as early-onset gastric cancer. Cox proportional hazard model was used to test the association between PRS and early-onset GC risk with early-onset age as the timescale and low genetic risk (PRS ≤ 20%) as the reference group. Results A total of 8 629 cases, including 6 284 males (72.82%) and 2 345 females (27.18%), were included, and the mean age was (60.61±10.80) years old. The PRS was negatively correlated with age of GC onset (r=-0.05, P<0.001). The mean age of gastric cancer cases with low, intermediate, and high genetic risk were (61.68±10.33), (60.53±10.79), (59.80±11.20), respectively. PRS was significantly associated with the risk of early-onset GC in a dose-response manner (intermediate genetic risk:HR=1.19, 95%CI:1.03-1.39, P=0.022; high genetic risk:HR=1.44, 95%CI:1.20-1.71, P<0.001). Conclusions PRS may contribute to the risk of both GC and early-onset GC. PRS can be used as a measurable indicator for risk prediction for occurrence and early-onset of GC. |
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