Incorporation of Genetic Expression of Airway Epithelium With CT Screening for Lung Cancer

Lung cancer, largely the result of cigarette smoking, is the leading cause of cancer death in the United States, killing over 160,000 people in 2010, more than breast, colorectal, and prostate cancer combined. Since only 10% of heavy smokers develop lung cancer and 20% of lung cancers develop in nonsmokers, it is thought that genetic predisposition plays an important role.

Without screening, lung cancer is only detected at an early stage 10% of the time, translating into a 7% cure rate. Published studies of screening for lung cancer using CT scans show that it is detectable at an early stage 85% of the time, translating into a cure rate over 60%. However, in a sample population of 1000 smokers over the age of 60 (high risk individuals), 233 will have suspicious abnormalities on CT scans, but only 27 had lung cancer. Two concerns are apparent. First, among the 233 individuals with suspicious abnormalities on CT, how does one choose the ones suspicious enough for biopsy, surgery, or other invasive procedures? Generally, follow-up CT scans over several months are used to assess the abnormalities for growth, since growth is a characteristic of malignancy. Unfortunately, repeated CT scans involve financial cost and potential radiation risk. An additional technique which is able to predict predisposition to lung cancer, if combined with the ability of CT scans to detect abnormalities in real time, could prove to be a powerful platform to efficiently screen for lung cancer and reduce its mortality.

Lung cancer develops as a consequence of a series of genetic injuries to the cells lining the airways which cause these bronchial cells to grow in a malignant manner, unchecked, resistant to normal homeostatic controls. By studying the gene expression signature of airway (bronchial) lining cells, differences are observed between normal nonsmokers, individuals exposed to smoke second-hand, and smokers who have developed COPD (chronic bronchitis and emphysema). Some genetic changes in bronchial lining cells near a lung cancer are specific to lung cancer --- the "field effect." Obtaining bronchial lining cells for genetic analysis requires an invasive and expensive procedure, fiberoptic bronchoscopy, and therefore bronchoscopically acquired bronchial lining cells are not suitable for screening of the public for lung cancer.

The lining cells of the nose, the nasal epithelium, which is part of the human airway, have many similarities to bronchial epithelium, but they are much more accessible. A gentle scraping of the nasal lining involves no risk to the patient, less cost, and, it is hoped, will provide the same genetic information as the bronchial lining cells.

This study proposes to examine the genetic correlation between nasal and bronchial epithelium in the hopes of developing an office-based test to identify a patient's risk for lung cancer. It is hoped that the genetic analysis of nasal epithelium may be combined with the other risk factors for lung cancer such as cigarette smoking, age over 50 years, and an obstructive ventilatory impairment noted on pulmonary function tests to find the ideal (or enriched) population to screen with CT to detect early lung cancer, thus reducing the financial cost, radiation exposure, and risk of invasive procedures to a minimum, furthering the ultimate goal of "personalized medicine."