Why some smokers develop lung cancer, but most do not, remains unclear. Answering this question is critical in improving prevention and early detection of this deadly disease. People with chronic obstructive pulmonary disease (COPD) have a much greater risk of developing lung cancer. Since smoking is the major cause of both COPD and lung cancer, these diseases likely arise from some common biological mechanisms that are activated by tobacco smoke. These mechanisms may be discovered by determining whether genetic characteristics associated with risk for developing COPD are also associated with risk for developing lung cancer. The primary goal of our study is to identify genetic characteristics that jointly contribute to COPD and lung cancer in smokers.
To achieve this, we will identify former and current smokers diagnosed with COPD, with lung cancer, or without either condition as participants from a large, stable, and well-characterized cohort of adult Kaiser Permanente Northern California health plan members. For all participants, survey data on lifestyle and behavioral characteristics, along with extensive genetic data, have already been collected. Genetic data include genome-wide single nucleotide polymorphism (SNP) genotyping and telomere length measures. In analyzing these data, we will first identify genetic characteristics associated with risk of COPD. We will then assess the extent to which COPD-related SNPs identified in this and prior studies and telomere length are associated with risk of (a) both COPD and lung cancer, (b) lung cancer with pre-existing COPD, and (c) lung cancer without pre-existing COPD.
The proposed study will be the most comprehensive examination of shared genetic risk factors for COPD and lung cancer to date. Identifying genetic characteristics associated with COPD and/or lung cancer has the potential to not only improve our understanding of the biological mechanisms involved in both tobacco-related diseases, but also lead to the discovery of new chemopreventive and therapeutic drugs and the development of tailored early detection strategies for lung cancer.