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Genetic risk, incident gastric cancer, and healthy lifestyle: a meta-analysis of genome-wide association studies and prospective cohort study

The lancet oncology, 2020-10, Vol.21 (10), p.1378-1386 [Tạp chí có phản biện]

2020 Elsevier Ltd ;Copyright © 2020 Elsevier Ltd. All rights reserved. ;2020. Elsevier Ltd ;ISSN: 1470-2045 ;EISSN: 1474-5488 ;DOI: 10.1016/S1470-2045(20)30460-5 ;PMID: 33002439

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Nhan đề:
Genetic risk, incident gastric cancer, and healthy lifestyle: a meta-analysis of genome-wide association studies and prospective cohort study
Tác giả: Jin, Guangfu ; Lv, Jun ; Yang, Ming ; Wang, Mengyun ; Zhu, Meng ; Wang, Tianpei ; Yan, Caiwang ; Yu, Canqing ; Ding, Yanbing ; Li, Gang ; Ren, Chuanli ; Ni, Jing ; Zhang, Ruoxin ; Guo, Yu ; Bian, Zheng ; Zheng, Yan ; 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
Chủ đề: Adult ; Aged ; Alcohol ; Asian People ; Cardiovascular disease ; China - epidemiology ; Datasets ; Disease prevention ; Female ; Follow-Up Studies ; Food consumption ; Gastric cancer ; Genetic analysis ; Genetic Predisposition to Disease - epidemiology ; Genetic Predisposition to Disease - genetics ; Genetic Predisposition to Disease - psychology ; Genetic variance ; Genome-Wide Association Study - statistics & numerical data ; Genomes ; Health behavior ; Health risk assessment ; Healthy Lifestyle ; Humans ; Incidence ; Lifestyles ; Male ; Meta-analysis ; Middle Aged ; Multifactorial Inheritance ; Polymorphism ; Polymorphism, Single Nucleotide ; Prospective Studies ; Risk Factors ; Single-nucleotide polymorphism ; Smoking ; Software ; Statistical analysis ; Stomach cancer ; Stomach Neoplasms - epidemiology ; Stomach Neoplasms - genetics ; Stomach Neoplasms - psychology
Là 1 phần của: The lancet oncology, 2020-10, Vol.21 (10), p.1378-1386
Mô tả: 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. 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 × 10−4 p=5 × 10−5 p=5 × 10−6 p=5 × 10−7, and p=5 × 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. The polygenic risk score derived from 112 single-nucleotide polymorphisms (p<5 × 10−5) showed the strongest association with gastric cancer risk (p=7·56 × 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 (ptrend<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 × 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 (ptrend<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). 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. National Key R&D Program of China, National Natural Science Foundation of China, 333 High-Level Talents Cultivation Project of Jiangsu Province, and China Postdoctoral Science Foundation.
Nơi xuất bản: England: Elsevier Ltd
Ngôn ngữ: English
Số nhận dạng: ISSN: 1470-2045
EISSN: 1474-5488
DOI: 10.1016/S1470-2045(20)30460-5
PMID: 33002439
Nguồn: MEDLINE
ProQuest Central

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Genetic risk, incident gastric cancer, and healthy lifestyle: a meta-analysis of genome-wide association studies and prospective cohort study

2020 Elsevier Ltd ;Copyright © 2020 Elsevier Ltd. All rights reserved. ;2020. Elsevier Ltd ;ISSN: 1470-2045 ;EISSN: 1474-5488 ;DOI: 10.1016/S1470-2045(20)30460-5 ;PMID: 33002439

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