title: Genetic variants in the SWI/SNF complex and smoking collaborate to modify the risk of pancreatic cancer in a Chinese population.
abstract: Pancreatic cancer (PC) is an aggressive malignancy with extremely low 5-year survival rate (<5%). SWItch/Sucrose Non Fermentable (SWI/SNF) complex is a core factor for chromatin-remodeling that utilize energy of ATP hydrolysis to mobilize nucleosomes, and modulate gene transcription. Recent studies have identified recurrent mutations in major components of SWI/SNF in a variety of human cancers, including PC. We conducted a two-stage case-control study to investigate the associations between 14 common variants in 6 genes (SMARCA4, SMCRB1, PBRM1, BRD7, ARID1, and ARID2) encoding major components of the SWI/SNF complex and the risk of PC. Three promising variants, rs11644043, rs11085754, and rs2073389 in the discovery stage comprising 310 cases and 457 controls were further genotyped in the validation stage containing 429 cases and 585 controls. rs11644043 in BRD7 and rs11085754 in SMARCA4 showed consistent significant association with increased risk of PC in both stages, with odds ratios (ORs) and 95% confidence interval (CI) of 2.04 (1.17-3.56) and 1.64 (1.16-2.33) in stage one, and 1.97 (1.24-3.14) and 1.45 (1.04-2.02) in stage two, respectively in a recessive model. Furthermore, the accumulative effects of rs11644043, rs11085754, and rs2073389 in SMARCB1 were observed (P for trend <0.0001). Intriguingly, gene-environmental interactions analysis consistently revealed the potential interactions of rs2073389 (P(add)  - FDR = 6.00 × 10(-4), P(mul)  - FDR = 1.50 × 10(-2)) and rs11085754 (P(add)  - FDR = 0.03) collaborating with smoking to modify the risk of PC. In conclusion, the current study provides evidence that genetic variants of SWI/SNF may contribute to the susceptibility of PC in the Chinese population.
authors.affiliation: State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment & Health, Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Beibei
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences; School of Basic Medicine Peking Union Medical College, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Tian
authors.affiliation: State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment & Health, Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhong
authors.affiliation: Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences; School of Basic Medicine Peking Union Medical College, Beijing, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Tian
authors.affiliation: State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment & Health, Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Division of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences; Peking Union Medical College, Beijing, China.
authors.forename: Jiaming
authors.initials: J
authors.lastname: Qian
authors.affiliation: State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment & Health, Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zou
authors.affiliation: Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences; School of Basic Medicine Peking Union Medical College, Beijing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment & Health, Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Na
authors.initials: N
authors.lastname: Shen
authors.affiliation: Division of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences; Peking Union Medical College, Beijing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment & Health, Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Lou
authors.affiliation: Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences; School of Basic Medicine Peking Union Medical College, Beijing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Qiu
authors.affiliation: State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment & Health, Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Juntao
authors.initials: J
authors.lastname: Ke
authors.affiliation: Division of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences; Peking Union Medical College, Beijing, China.
authors.forename: Xinghua
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences; School of Basic Medicine Peking Union Medical College, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Song
authors.affiliation: Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences; School of Basic Medicine Peking Union Medical College, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Epidemiology and Biostatistics and Guangdong Key Lab of Molecular Epidemiology, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences; School of Basic Medicine Peking Union Medical College, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment & Health, Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Miao
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics; D004268:DNA-Binding Proteins; D005260:Female; D059647:Gene-Environment Interaction; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D014157:Transcription Factors / Q000235:genetics; D000092468:Bromodomain Containing Proteins
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004265:DNA Helicases; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C112476:ARID1A protein, human; C512511:ARID2 protein, human; C485694:BRD7 protein, human; D000092468:Bromodomain Containing Proteins; C102195:PBRM1 protein, human; C084108:SMARCA4 protein, human
keywords: SWI/SNF complex; gene-environmental interactions; genetic variants; pancreatic cancer; susceptibility