title: BRM polymorphisms, pancreatic cancer risk and survival.
abstract: Variant alleles of two promoter polymorphisms in the BRM gene (BRM-741, BRM-1321), create MEF2D transcription binding sites that lead to epigenetic silencing of BRM, the key catalytic component of the SWI/SNF chromatin remodeling complex. BRM suppression can be reversed pharmacologically.(1) Our group and others have reported associations with lung, head and neck, hepatocellular cancer risk,(1-3) and with lung and esophageal cancer prognosis (ASCO 2013; abstract 11057 & 4077). Herein, we assessed risk and survival associations with pancreatic cancer. A provincial population-based case-control study was conducted with 623 histologically confirmed pancreatic adenocarcinoma cases and 1,192 age/gender distribution-matched controls.(4) Survival of cases was obtained through the Ontario Cancer Registry. Logistic and Cox proportional hazard regression models were fitted, adjusting for relevant covariates. Median age was 65 y; 52% were male; Stage I (8%), II (55%), III (14%), IV (23%); 53% after curative resection, 79% after chemotherapy; and 83% had died. In the risk analysis, adjusted odds ratios (aOR) were 1.01 (95% CI: 0.1-2.0) and 0.96 (95% CI: 0.7-1.3) for the homozygotes of BRM-741 and BRM-1321, respectively; aOR of double-homozygotes was 1.11 (95% CI: 0.80-1.53), compared to the double-wildtype. For the survival analysis, adjusted hazard ratios (aHR) were 2.19 (95% CI: 1.9-2.5) for BRM-741 and 1.94 (95% CI: 1.7-2.2) for BRM-1321, per unit increase in variant alleles. Compared with the double-wildtype, aHR for carrying no, one, and two double-homozygotes were 2.14 (95% CI: 1.6-2.8), 4.17 (95% CI: 3.0-5.7), 8.03 (95% CI: 5.7-11.4), respectively. In conclusion, two functional promoter BRM polymorphisms were not associated with pancreatic adenocarcinoma risk, but are strongly associated with survival.
authors.affiliation: Department of Surgery, University of British Columbia, Vancouver, BC, Canada.|Princess Margaret Cancer Centre-University Health Network-Ontario Cancer Institute, University of Toronto, Toronto, ON, Canada.
authors.forename: Maja
authors.initials: M
authors.lastname: Segedi
authors.affiliation: Mount Sinai Hospital-Lunenfeld Research Institute, Toronto, ON, Canada.
authors.forename: Laura N
authors.initials: LN
authors.lastname: Anderson
authors.affiliation: Princess Margaret Cancer Centre-University Health Network-Ontario Cancer Institute, University of Toronto, Toronto, ON, Canada.
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Espin-Garcia
authors.affiliation: Princess Margaret Cancer Centre-University Health Network-Ontario Cancer Institute, University of Toronto, Toronto, ON, Canada.|Mount Sinai Hospital-Lunenfeld Research Institute, Toronto, ON, Canada.
authors.forename: Ayelet
authors.initials: A
authors.lastname: Borgida
authors.affiliation: Princess Margaret Cancer Centre-University Health Network-Ontario Cancer Institute, University of Toronto, Toronto, ON, Canada.|Mount Sinai Hospital-Lunenfeld Research Institute, Toronto, ON, Canada.
authors.forename: Teresa
authors.initials: T
authors.lastname: Bianco
authors.affiliation: Princess Margaret Cancer Centre-University Health Network-Ontario Cancer Institute, University of Toronto, Toronto, ON, Canada.
authors.forename: Dangxiao
authors.initials: D
authors.lastname: Cheng
authors.affiliation: Princess Margaret Cancer Centre-University Health Network-Ontario Cancer Institute, University of Toronto, Toronto, ON, Canada.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Princess Margaret Cancer Centre-University Health Network-Ontario Cancer Institute, University of Toronto, Toronto, ON, Canada.
authors.forename: Devalben
authors.initials: D
authors.lastname: Patel
authors.affiliation: Princess Margaret Cancer Centre-University Health Network-Ontario Cancer Institute, University of Toronto, Toronto, ON, Canada.
authors.forename: M Catherine
authors.initials: MC
authors.lastname: Brown
authors.affiliation: Princess Margaret Cancer Centre-University Health Network-Ontario Cancer Institute, University of Toronto, Toronto, ON, Canada.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Medical Oncology, University of Florida, Gainesville, FL.
authors.forename: David
authors.initials: D
authors.lastname: Reisman
authors.affiliation: Princess Margaret Cancer Centre-University Health Network-Ontario Cancer Institute, University of Toronto, Toronto, ON, Canada.|Mount Sinai Hospital-Lunenfeld Research Institute, Toronto, ON, Canada.
authors.forename: Steven
authors.initials: S
authors.lastname: Gallinger
authors.affiliation: Prevention and Cancer Control, Cancer Care Ontario, Toronto, ON, Canada.
authors.forename: Michelle
authors.initials: M
authors.lastname: Cotterchio
authors.affiliation: Mount Sinai Hospital-Lunenfeld Research Institute, Toronto, ON, Canada.
authors.forename: Rayjean
authors.initials: R
authors.lastname: Hung
authors.affiliation: Princess Margaret Cancer Centre-University Health Network-Ontario Cancer Institute, University of Toronto, Toronto, ON, Canada. Geoffrey.Liu@uhn.ca.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Liu
authors.affiliation: Princess Margaret Cancer Centre-University Health Network-Ontario Cancer Institute, University of Toronto, Toronto, ON, Canada.|Mount Sinai Hospital-Lunenfeld Research Institute, Toronto, ON, Canada.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Cleary
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality; D000367:Age Factors; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009864:Ontario / Q000453:epidemiology; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000401:mortality; D011110:Polymorphism, Genetic; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012737:Sex Factors; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C084011:SMARCA2 protein, human; D014157:Transcription Factors