Bridging the clinical gaps: genetic, epigenetic and transcriptomic biomarkers for the early detection of lung cancer in
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REVIEW
Open Access
Bridging the clinical gaps: genetic, epigenetic and transcriptomic biomarkers for the early detection of lung cancer in the post-National Lung Screening Trial era John F Brothers1,2*†, Kahkeshan Hijazi1,2†, Celine Mascaux3, Randa A El-Zein4, Margaret R Spitz4 and Avrum Spira1,2
Abstract Lung cancer is the leading cause of cancer death worldwide in part due to our inability to identify which smokers are at highest risk and the lack of effective tools to detect the disease at its earliest and potentially curable stage. Recent results from the National Lung Screening Trial have shown that annual screening of high-risk smokers with low-dose helical computed tomography of the chest can reduce lung cancer mortality. However, molecular biomarkers are needed to identify which current and former smokers would benefit most from annual computed tomography scan screening in order to reduce the costs and morbidity associated with this procedure. Additionally, there is an urgent clinical need to develop biomarkers that can distinguish benign from malignant lesions found on computed tomography of the chest given its very high false positive rate. This review highlights recent genetic, transcriptomic and epigenomic biomarkers that are emerging as tools for the early detection of lung cancer both in the diagnostic and screening setting. Keywords: Biomarker, Diagnostics, Early detection, Epigenetics, Genetics, Lung cancer, Screening, Transcriptomics
Review Introduction
Lung cancer is the leading cause of cancer death in both men and women in the US and the world, causing more than 1 million deaths per year [1-4]. The global cancer burden in annual cases is projected to double by 2050, and lung cancer is expected to remain the leading cause of all cancer deaths during that time. Cigarette smoke remains the main risk factor for lung cancer, with 85% to 90% percent of lung cancer cases in the US occurring in current or former smokers. However, only 10% to 20% of heavy smokers develop lung cancer [5]. While smoking cessation gradually reduces the risk of lung cancer, the majority of new lung cancer cases occur in former smokers. The high mortality in patients with * Correspondence: [email protected] † Equal contributors 1 Bioinformatics Program, Boston University, Boston, MA, USA 2 Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA Full list of author information is available at the end of the article
lung cancer (80% to 85% in five years) results in part from our inability to predict which of the 100 million current and former smokers in the US are at greatest risk for developing lung cancer, and from the lack of effective tools to diagnose the disease at an early stage [6]. Recent results published from the National Lung Screening Trial have shown that screening high-risk smokers (based on age and cumulative exposure to tobacco smoke) with low-dose helical computed tomography (CT) can lead to a reduction in both lung cancer mortality (by 20.0%) and all-
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