Department of Otolaryngology-Head and Neck Surgery, University Health Network, Princess Margaret Hospital, Toronto, Ontario M5G 2M9, Canada.
Carcinogenesis. 2013 May;34(5):1012-7. doi: 10.1093/carcin/bgt008. Epub 2013 Jan 15.
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.
SWI/SNF 染色质重塑复合物是一种重要的基因表达调控因子，与癌症的发生发展有关。BRM（SWI/SNF 的关键催化亚基）的表达在各种实体瘤中丢失。两种新的 BRM 启动子多态性（BRM-741 和 BRM-1321）与 BRM 缺失和癌症风险升高相关。本研究旨在检测头颈部鳞状细胞癌（HNSCC）中的 BRM 表达，并将 BRM 多态性与 HNSCC 风险相关联。对 8 种 HNSCC 细胞系和 76 例手术切除的肿瘤样本进行了 BRM 表达研究。对 668 例 HNSCC 患者（口腔、口咽、喉和下咽）和 700 例健康匹配对照进行了病例对照研究。在 25%的细胞系和 16%的肿瘤中，BRM 表达缺失。每种多态性的纯合基因型与 HNSCC 风险增加显著相关[BRM-741：调整后的优势比（aOR）1.75，95%置信区间（CI）1.2-2.3，P<0.001；BRM-1321：aOR 1.65，95%CI 1.2-2.2，P<0.001]。同时携带两种 BRM 多态性的个体患 HNSCC 的风险增加了两倍以上（aOR 2.23，95%CI 1.5-3.4，P<0.001）。对于同时携带两种纯合变体的 HPV 阳性口咽癌亚组，风险尤其升高（aOR 3.09，95%CI 1.5-6.8，P=0.004）。BRM 启动子多态性似乎是 HNSCC 的易感标志物，在筛查、预防和治疗方面具有潜在的应用价值。
