title: Association of two BRM promoter polymorphisms with head and neck squamous cell carcinoma risk.
abstract: The SWI/SNF chromatin remodeling complex is an important regulator of gene expression that has been linked to cancer development. Expression of Brahma (BRM), a critical catalytic subunit of SWI/SNF, is lost in a variety of solid tumors. Two novel BRM promoter polymorphisms (BRM-741 and BRM-1321) have been correlated with BRM loss and elevated cancer risk. The aim(s) of this study were to examine BRM expression in head and neck squamous cell carcinoma (HNSCC) and to correlate BRM polymorphisms with HNSCC risk. BRM expression studies were performed on eight HNSCC cell lines and 76 surgically resected tumor samples. A case-control study was conducted on 668 HNSCC patients (oral cavity, oropharynx, larynx and hypopharynx) and 700 healthy matched controls. BRM expression was lost in 25% of cell lines and 16% of tumors. The homozygous genotype of each polymorphism was significantly associated with increased HNSCC risk [BRM-741: adjusted odds ratio (aOR) 1.75, 95% CI 1.2-2.3, P < 0.001; BRM-1321: aOR 1.65, 95% CI 1.2-2.2, P < 0.001]. Individuals that were homozygous for both BRM polymorphisms had a more than 2-fold increase in the risk of HNSCC (aOR 2.23, 95% CI 1.5-3.4, P < 0.001). A particularly elevated risk was seen within the oropharynx, human papillomavirus-positive subgroup for carriers of both homozygous variants (aOR 3.09, 95% CI 1.5-6.8, P = 0.004). BRM promoter polymorphisms appear to act as susceptibility markers of HNSCC with potential utility in screening, prevention and treatment.
authors: Department of Otolaryngology-Head and Neck Surgery, University Health Network, Princess Margaret Hospital, Toronto, Ontario M5G 2M9, Canada. jennyr.wang@utoronto.ca
authors: Jennifer R
authors: JR
authors: Wang
authors: Sarah J B
authors: SJ
authors: Gramling
authors: David P
authors: DP
authors: Goldstein
authors: Dangxiao
authors: D
authors: Cheng
authors: Duoduo
authors: D
authors: Chen
authors: Abul K
authors: AK
authors: Azad
authors: Alvina
authors: A
authors: Tse
authors: Henrique
authors: H
authors: Hon
authors: Zhuo
authors: Z
authors: Chen
authors: Maryam
authors: M
authors: Mirshams
authors: Colleen
authors: C
authors: Simpson
authors: Shao Hui
authors: SH
authors: Huang
authors: Stephanie
authors: S
authors: Marquez
authors: Brian
authors: B
authors: O'Sullivan
authors: Fei-Fei
authors: FF
authors: Liu
authors: Heidi
authors: H
authors: Roberts
authors: Wei
authors: W
authors: Xu
authors: Dale H
authors: DH
authors: Brown
authors: Ralph W
authors: RW
authors: Gilbert
authors: Patrick J
authors: PJ
authors: Gullane
authors: Jonathan C
authors: JC
authors: Irish
authors: David N
authors: DN
authors: Reisman
authors: Geoffrey
authors: G
authors: Liu
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D000077195:Squamous Cell Carcinoma of Head and Neck; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C084011:SMARCA2 protein, human; D014157:Transcription Factors