Genetic evidence linking lung cancer and COPD: a new perspective

Robert P Young^1,4, Raewyn J Hopkins¹, Gregory D Gamble¹, Carol Etzel², Randa El-Zein², James D Crapo^3
1Department of Medicine and School of Biological Sciences, University of Auckland, Auckland, New Zealand; ²Department of Epidemiology, UT MD Anderson Cancer Center, Houston, TX, USA; ³National Jewish Health, Denver, CO, USA; ⁴Synergenz Biosciences Ltd, Auckland, New Zealand

Abstract: Epidemiological studies indicate that tobacco smoke exposure accounts for nearly 90% of cases of chronic obstructive pulmonary disease (COPD) and lung cancer. However, genetic factors may explain why 10%–30% of smokers develop these complications. This perspective reviews the evidence suggesting that COPD is closely linked to susceptibility to lung cancer and outlines the potential relevance of this observation. Epidemiological studies show that COPD is the single most important risk factor for lung cancer among smokers and predates lung cancer in up to 80% of cases. Genome-wide association studies of lung cancer, lung function, and COPD have identified a number of overlapping “susceptibility” loci. With stringent phenotyping, it has recently been shown that several of these overlapping loci are independently associated with both COPD and lung cancer. These loci implicate genes underlying pulmonary inflammation and apoptotic processes mediated by the bronchial epithelium, and link COPD with lung cancer at a molecular genetic level. It is currently possible to derive risk models for lung cancer that incorporate lung cancer-specific genetic variants, recently identified “COPD-related” genetic variants, and clinical variables. Early studies suggest that single nucleotide polymorphism-based risk stratification of smokers might help better target novel prevention and early diagnostic strategies in lung cancer.

Keywords: lung cancer, chronic obstructive pulmonary disease, association study, single nucleotide polymorphism, risk model