Genetic variants in the SWI/SNF complex and smoking collaborate to modify the risk of pancreatic cancer in a Chinese population

摘要: Pancreatic cancer (PC) is an aggressive malignancy with extremely low 5-year survival rate (<5%). SWItch/Sucrose Non Fermentable (SWI/SNF) complex 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 SWI/SNF variety human cancers, including PC. We conducted two-stage case–control study investigate the associations between 14 common variants 6 genes (SMARCA4, SMCRB1, PBRM1, BRD7, ARID1, ARID2) encoding risk Three promising variants, rs11644043, rs11085754, rs2073389 discovery stage comprising 310 cases 457 controls were further genotyped validation containing 429 585 controls. rs11644043 BRD7 rs11085754 SMARCA4 showed consistent significant association increased PC both stages, odds ratios (ORs) 95% confidence interval (CI) 2.04 (1.17–3.56) 1.64 (1.16–2.33) one, 1.97 (1.24–3.14) 1.45 (1.04–2.02) two, respectively recessive model. Furthermore, accumulative effects SMARCB1 observed (P trend <0.0001). Intriguingly, gene-environmental interactions analysis consistently revealed potential (Padd − FDR = 6.00 × 10−4, Pmul − FDR = 1.50 × 10−2) (Padd − FDR = 0.03) collaborating smoking modify In conclusion, current provides evidence genetic may contribute susceptibility Chinese population. © 2014 Wiley Periodicals, Inc.