Discovery of BRM Promoter Polymorphisms: Importance in Risk Stratification and Clinical Application

Abstract

Lung cancer is the most common cause of all cancer deaths in the United States and worldwide. Despite advances in surgical techniques and therapies, the cure rates for lung cancer have not changed in the last thirty years. Lung cancer typically presents in the advanced stages when the cancer has already spread beyond the chest wall. Therefore, a goal of clinicians is to treat these patients while their lung cancers are at an earlier stage. The screening of smokers and former smokers by computed tomography (CT) is usually the recommended approach in order to detect early-stage lung cancer. However, given that only a small percentage of smokers will get lung cancer, researchers have sought to determine the causes of lung cancer other than tobacco exposure. Throughout the past decade, investigators have attempted to find suitable biomarkers to determine cancer risk so that individuals can be risk-stratified prior to screening. This process would target a much more specific at-risk population and would minimize the risks of CT and other diagnostic modalities in those individuals who are not at the highest risk. The polymorphisms in the promoter of the Brahma (BRM) gene are two candidate biomarkers that have been associated with loss of the tumor susceptibility protein BRM, which in turn is correlated with an increase in cancer risk. Much progress has been made since the initial discovery of these polymorphisms in 2011, and the aim of this commentary is to review the discovery of the BRM polymorphisms and to discuss their pertinence to clinical practice.