Grant: Travel Awards - Institute Community Support

Chronic obstructive pulmonary disease (COPD) affects about 10% of Canadian adults. People with COPD are two to four times more likely to develop lung cancer than those without the disease. Lung cancer is the leading cause of cancer death worldwide. Yet the biological reason why COPD increases lung cancer risk remains unclear, and doctors currently have no reliable way to identify which individuals with COPD are most likely to develop the disease. Low-dose CT (LDCT) can detect cancer earlier, but with COPD being so common, screening everyone isn't feasible. Heavy CT use strains the health system, increases radiation exposure, and produces many false positives that cause anxiety and extra testing. As a result, some high-risk COPD patients may not be screened in time. To address this, we aim to develop and validate an Airway Biological Risk Score to identify COPD patients at the highest near-term risk for lung cancer. Small airways are the earliest and most severely affected region in COPD, and we hypothesized that this vulnerable area could carry early molecular changes linking COPD to cancer. Using small-airway samples from people with and without COPD, we discovered an "early warning signal": a group of cell-division genes centered on a gene called PLK4. When overly active, PLK4 causes cells to make mistakes and gain or lose chromosomes (changes often seen in early cancer). We found this PLK4-related signal in both COPD airways and in lung cancer tissue. We also detected chromosome problems in thousands of sputum samples from COPD patients without cancer and observed the same signal in pre-cancer lesions, becoming stronger as the disease progressed. We are now validating this signature in a rare BC Cancer cohort of bronchial brushings collected from COPD and non-COPD patients before and after lung cancer diagnosis. This cohort will help determine whether these early airway changes predict who will develop lung cancer and ultimately improve diagnosis and outcomes.