Collectively, lung cancer and chronic obstructive pulmonary disease (COPD) are the leading causes of death related to lung disease in the US. Lung cancer is now the primary cause of cancer death in both men and women, and increasingly occurs in people who have never smoked and in former smokers. Published reports indicate that the presence of COPD independently increases the risk of lung cancer three- to ten-fold. COPD is estimated to affect nearly 25 million people in the U.S., but less than half of these individuals have been diagnosed and more than four million have never smoked. COPD currently is the fourth leading cause of mortality in the U.S .and is projected to be the third in five years. In a substantial proportion of patients with lung cancer, chronic airflow obstruction precedes the development of lung cancer, but whether it actually lies on the causal pathway remains unknown. Thus while smoking causes both COPD and lung cancer, COPD itself provides a fertile substrate for lung carcinogenesis by either harboring or nurturing oncogenic lesions. Many smokers quit at the onset of COPD, but remain at risk for often-lethal lung cancer. New knowledge combining comprehensive genome-wide information with systems biology approaches has high potential to identify which COPD patients are at risk of lung cancer, so that promising approaches to chemo-prevention and early interdiction can be tested.
This project aims to develop such new predictive and diagnostic strategies. These researchers hypothesize that linking precise clinical phenotypes (magnitude and pattern of airflow limitation and emphysematous tissue damage) to specific germ line and somatic genetic alterations will enable improved prediction of lung cancer risk and early diagnosis; provide opportunities to test innovative preventive strategies; and identify new molecular targets for the treatment of COPD and lung cancer.
The four specific aims of this project are:
- Define the clinical disease phenotypes of COPD and lung cancer
- Define lung gene expression within the disease phenotypes of COPD and lung cancer
- Define germ line genetic alterations within the disease phenotypes of COPD and lung cancer
- Construct models combining multilevel -omics data with GWAS and COPD clinical phenotypes that predict susceptible (and resistant) phenotypes for lung carcinoma