Association of BRM promoter polymorphisms and esophageal adenocarcinoma outcome

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2017

Erschienen:

2017

Enthalten in:

Zur Gesamtaufnahme - volume:8

Enthalten in:

Oncotarget - 8(2017), 17 vom: 25. Apr., Seite 28093-28100

Sprache:

Englisch

Beteiligte Personen:

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

Links:

Volltext

Themen:

Brahma
Cancer prognosis
Chromatin remodeling
Esophageal cancer
Journal Article
Polymorphism
SMARCA2 protein, human
Transcription Factors

Anmerkungen:

Date Completed 05.03.2018

Date Revised 13.11.2018

published: Print

Citation Status MEDLINE

doi:

10.18632/oncotarget.15890

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM271137665