Association of BRM promoter polymorphisms and esophageal adenocarcinoma outcome
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Grzegorz J. Korpanty1,2,*, Lawson Eng1,*, Xin Qiu3,*, Olusola Olusesan Faluyi1, Daniel J. Renouf4, Dangxiao Cheng5, Devalben Patel5, Zhuo Chen5, Brandon C. Tse5, Jennifer J. Knox1, Lorin Dodbiba1, Jennifer Teichman1, Abul Kalam Azad1, Rebecca Wong6, Gail Darling7, David Reisman8, Sinead Cuffe1,#, Geoffrey Liu1,5,9,#, Wei Xu3,#
1Princess Margaret Cancer Centre, Department of Medicine, University Health Network, Toronto, ON, Canada
2Canadian Cancer Trials Group, Department of Medicine, Queens University, Kingston, ON, Canada
3Princess Margaret Cancer Centre, Department of Biostatistics, University Health Network, Toronto, ON, Canada
4Department of Medical Oncology, University of British Columbia and British Columbia Cancer Agency, Vancouver, BC, Canada
5Princess Margaret Cancer Centre, Department of Medical Biophysics, University Health Network, Toronto, ON, Canada
6Princess Margaret Cancer Centre, Radiation Medicine Program, University Health Network, Toronto, ON, Canada
7Department of Surgery, Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, ON, Canada
8Department of Medicine in the College of Medicine, Division of Hematology and Oncology, University of Florida, Gainesville, FL, USA
9Department of Epidemiology, Dalla Lana School of Pubic Health, Toronto, ON, Canada
Geoffrey Liu, email: Geoffrey.Liu@uhn.on.ca
Keywords: chromatin remodeling, polymorphism, cancer prognosis, esophageal cancer, brahma
Received: October 20, 2016 Accepted: February 22, 2017 Published: March 03, 2017
Purpose: Brahma (BRM) is a critical catalytic subunit of the SWI/SNF chromatin remodeling complex; expression of BRM is commonly lost in various cancer types. BRM promoter polymorphisms (BRM-741; BRM-1321) are associated with loss of BRM expression, and with cancer risk/survival. We evaluated these two polymorphisms in the overall survival (OS) of esophageal adenocarcinoma (EAC) patients.
Results: Of 270 patients, 37% were stage IV. Minor allele frequencies were 47−49%; 15% were double-homozygotes. When compared to the wild-type genotype, the homozygous variant of BRM-741 carried an adjusted OS hazard ratio (aHR) of 1.64 (95% CI:1.1−2.4); for BRM-1321, the aHR was 2.09 (95% CI:1.4−3.0). Compared to the double wild-type, carrying homozygous variants of both promoter polymorphisms (double-homozygote) yielded an aHR of 2.21 (95% CI:1.4−3.6). Directions/magnitudes of associations were similar in subsets by age, gender, smoking status, use of platinum agents, and disease stage, and for progression-free survival.
Materials and Methods: In a cohort of EAC patients of all stages (84% male; median age of 64 years), two BRM polymorphisms were genotyped. Cox proportional hazards models, adjusted for known prognostic variables, estimated the association of polymorphisms with OS.
Conclusions: BRM polymorphisms were associated with OS in EAC in this study. Validation studies are warranted.
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