title: Imputation-based association analyses identify new lung cancer susceptibility variants in CDK6 and SH3RF1 and their interactions with smoking in Chinese populations.
abstract: Cell cycle regulation, apoptosis, oxidative stress and inflammation response play critical roles in the development of smoking-induced lung cancer. However, it is still not well known whether their genetic variants are associated with lung cancer susceptibility. In this study, we performed imputation-based association analyses to investigate the influence of common genetic variants in these pathways and their interactions with smoking on lung cancer susceptibility. We first selected 24 042 unvalidated genetic variants in 798 genes from the imputed dataset of the previous lung cancer genome-wide association study in 2331 cases and 3077 controls, and then conducted additional two-stage validations in 4133 cases and 4522 controls. We found a genome-wide significant (P < 5.0 × 10(-8)) association for rs2282987 in CDK6 at 7q21.2 [odds ratio (OR) = 1.18, combined P add = 2.27 × 10(-9)] and a consistent association for rs2706748 in SH3RF1 at 4q32.3 (OR = 1.17, combined P add = 5.10 × 10(-6)). Interaction analyses showed that rs2282987 and rs2706748 interacted with both smoking status (P interaction were 1.04 × 10(-2) and 3.03 × 10(-2), respectively) and smoking history (P interaction were 1.21 × 10(-2) and 5.21 × 10(-2), respectively) to contribute to lung cancer susceptibility in subjects aged 51-60 years. These results further underscore the contribution of genetic variants involved in pathways of cell cycle regulation and apoptosis to lung cancer susceptibility, and highlight gene-environment interactions in lung cancer etiology, especially in subjects aged 51-60 years.
authors: Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China.
authors: Qifei
authors: Q
authors: Deng
authors: Huan
authors: H
authors: Guo
authors: Juncheng
authors: J
authors: Dai
authors: Lei
authors: L
authors: Yang
authors: Chen
authors: C
authors: Wu
authors: Qing
authors: Q
authors: Wang
authors: Zhibin
authors: Z
authors: Hu
authors: Ming
authors: M
authors: Yang
authors: Li
authors: L
authors: Liu
authors: Dianke
authors: D
authors: Yu
authors: Die
authors: D
authors: Hu
authors: Xiaohua
authors: X
authors: Hong
authors: Fuman
authors: F
authors: Qiu
authors: Handong
authors: H
authors: Yang
authors: Tian
authors: T
authors: Wang
authors: Wen
authors: W
authors: Tan
authors: Minjie
authors: M
authors: Chu
authors: Jing
authors: J
authors: Feng
authors: Kai
authors: K
authors: Teng
authors: Jianhang
authors: J
authors: Gong
authors: Chongqi
authors: C
authors: Sun
authors: Xiaoyan
authors: X
authors: Hu
authors: Kai
authors: K
authors: Zhang
authors: Jiachun
authors: J
authors: Lu
authors: Dongxin
authors: D
authors: Lin
authors: Hongbing
authors: H
authors: Shen
authors: Tangchun
authors: T
authors: Wu
mesh_terms: D002681:China; D051361:Cyclin-Dependent Kinase 6 / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: C498193:SH3RF1 protein, human; D044767:Ubiquitin-Protein Ligases; C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6