Association of BRM promoter polymorphisms and esophageal adenocarcinoma outcome Academic Article uri icon

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abstract

  • 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.

authors

  • Korpanty, Grzegorz J
  • Eng, Lawson
  • Qiu, Xin
  • Faluyi, Olusola Olusesan
  • Renouf, Daniel J
  • Cheng, Dangxiao
  • Patel, Devalben
  • Chen, Zhuo
  • Tse, Brandon C
  • Knox, Jennifer J
  • Dodbiba, Lorin
  • Teichman, Jennifer
  • Azad, Abul Kalam
  • Wong, Raimond
  • Darling, Gail
  • Reisman, David
  • Cuffe, Sinead
  • Liu, Geoffrey
  • Xu, Wei

publication date

  • April 25, 2017