| Title | Genetic risk, incident gastric cancer, and healthy lifestyle: a meta-analysis of genome-wide association studies and prospective cohort study |
| Authors | Jin, Guongfu Lv, Jun Yang, Ming Wang, Mengyun Zhu, Meng Wang, Tionpei Yan, Caiwang Yu, Canqing Ding, Yanbing Li, Gang Ren, Chuanli Ni, Jing Zhang, Ruoxin Guo, Yu Bian, Zheng Zheng, Yon Zhang, Nasha Jiang, Yue Chen, Jiaping Wang, Yanong Xu, Dazhi Zheng, Hong Yang, Ling Chen, Yiping Walters, Robin Millwood, Iona Y. Dai, Juncheng Ma, Hongxia Chen, Kexin Chen, Zhengming Hu, Zhibin Wei, Qingyi Shen, Hongbing Li, Liming |
| Affiliation | Nanjing Med Univ, Sch Publ Hlth, Ctr Global Hlth, Dept Epidemiol, Nanjing 211166, Peoples R China Nanjing Med Univ, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Collaborat Innovat Ctr ForCamer Personalized Med, Nanjing, Peoples R China Nanjing Med Univ, China Int Cooperat Ctr Environm & Human Hlth, Nanjing, Peoples R China Peking Univ, Hlth Sci Ctr, Sch Publ Hlth, Dept Epidemiol & Biostat, Beijing, Peoples R China Shandong First Med Univ, Shandong Canc Hosp & Inst, Canc Res Ctr, Shandong Prov Key Lab Radiat Oncol, Jinan, Peoples R China Shandong Acad Med Sci, Jinan, Peoples R China Fudan Univ, Shanghai CancerCtr, Canc Inst, Shanghai, Peoples R China Fudan Univ, Dept Gastr Canc, Shanghai Med Coll, Shanghai CancerCtr, Shanghai, Peoples R China Yangzhou Univ, Dept Gastroenterol, Affiliated Hosp, Yangzhou, Jiangsu, Peoples R China Nanjing Med Univ, Dept Gen Surg, Jiangsu Inst Canc Res, Affiliated Canc Hosp,Jiangsu Canc Hosp, Nanjing, Peoples R China Yangzhou Univ, Dept Lab Med, Clin Med Coll, Yangzhou, Jiangsu, Peoples R China Chinese Acad Med Sci, Beijing, Peoples R China Fudan Univ, Dept Gastr Surg, Shanghai Canc Ctr, Shanghai, Peoples R China Tianjin Med Univ, Tianjin Med Univ Canc Inst & Hosp, Key Lab Mol Canc Epidemiol Tianjin, Dept Epidemiol & Biostat,Natl Clin Res Ctr Canc, Tianjin, Peoples R China Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford, England Duke Univ, Duke Canc Inst, Med Ctr, Durham, NC USA Duke Univ, Sch Med, Dept Populat Hlth Sci, Durham, NC USA |
| Keywords | EVENTS CHINA DISEASE ACCURACY KADOORIE MODELS |
| Issue Date | Oct-2020 |
| Publisher | LANCET ONCOLOGY |
| Abstract | Background Genetic variants and lifestyle factors have been associated with gastric cancer risk, but the extent to which an increased genetic risk can be offset by a healthy lifestyle remains unknown. We aimed to establish a genetic risk model for gastric cancer and assess the benefits of adhering to a healthy lifestyle in individuals with a high genetic risk. Methods In this meta-analysis and prospective cohort study, we first did a fixed-effects meta-analysis of the association between genetic variants and gastric cancer in six independent genome-wide association studies (GWAS) with a case-control study design. These GWAS comprised 21 168 Han Chinese individuals, of whom 10 254 had gastric cancer and 10 914 geographically matched controls did not. Using summary statistics from the meta-analysis, we constructed five polygenic risk scores in a range of thresholds (p=5 x 10(-4), p=5 x 10(-5), p=5 x 10(-6), p=5 x 10(-7), and p=5 x 10(-8)) for gastric cancer. We then applied these scores to an independent, prospective, nationwide cohort of 100 220 individuals from the China Kadoorie Biobank (CKB), with more than 10 years of follow-up. The relative and absolute risk of incident gastric cancer associated with healthy lifestyle factors (defined as not smoking, never consuming alcohol, the low consumption of preserved foods, and the frequent intake of fresh fruits and vegetables), was assessed and stratified by genetic risk (low [quintile 1 of the polygenic risk score], intermediate [quintile 2-4 of the polygenic risk score], and high [quintile 5 of the polygenic risk score]). Individuals with a favourable lifestyle were considered as those who adopted all four healthy lifestyle factors, those with an intermediate lifestyle adopted two or three factors, and those with an unfavourable lifestyle adopted none or one factor. Findings The polygenic risk score derived from 112 single-nucleotide polymorphisms (p<5 x 10(-5)) showed the strongest association with gastric cancer risk (p=7.56 x 10(-10)). When this polygenic risk score was applied to the CKB cohort, we found that there was a significant increase in the relative risk of incident gastric cancer across the quintiles of the polygenic risk score (p(trend)<0.0001). Compared with individuals who had a low genetic risk, those with an intermediate genetic risk (hazard ratio [HR] 1.54 [95% CI 1.22-1.94], p=2.67 x 10(-4)) and a high genetic risk (2.08 [1.61-2.69], p<0.0001) had a greater risk of gastric cancer. A similar increase in the relative risk of incident gastric cancer was observed across the lifestyle categories (p(trend)<0.0001), with a higher risk of gastric cancer in those with an unfavourable lifestyle than those with a favourable lifestyle (2.03 [1.46-2.83], p<0.0001). Participants with a high genetic risk and a favourable lifestyle had a lower risk of gastric cancer than those with a high genetic risk and an unfavourable lifestyle (0.53 [0.29-0.99], p=0.048), with an absolute risk reduction of 1.12% (95% CI 0.62-1.56). Interpretation Chinese individuals at an increased risk of incident gastric cancer could be identified by use of our newly developed polygenic risk score. Compared with individuals at a high genetic risk who adopt an unhealthy lifestyle, those who adopt a healthy lifestyle could substantially reduce their risk of incident gastric cancer. Copyright (C) 2020 Elsevier Ltd. All rights reserved. |
| URI | http://hdl.handle.net/20.500.11897/592539 |
| ISSN | 1470-2045 |
| Indexed | SCI(E) |
| Appears in Collections: | 医学部待认领 |
