Circulating Markers of Interstitial Lung Disease and Subsequent Risk of Lung Cancer

Background: Inflammation and pulmonary diseases, including interstitial lung diseases, are associated with increased lung cancer risk. Circulating levels of surfactant protein-D (SP-D) and Krebs von Lungren-6 (KL-6) are elevated in interstitial lung disease patients and may be useful markers of processes contributing to lung cancer. Methods: We conducted a nested case-control study, including 532 lung cancer cases, 582 matched controls, and 150 additional controls with chest X-ray (CXR) evidence of pulmonary scarring, in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Serum SP-D and KL-6 levels were measured using enzyme immunoassay. Logistic regression was used to estimate the associations of SP-D and KL-6 with lung cancer and CXR scarring. Results: Cases had higher levels than controls for SP-D (median 118.7 vs. 105.4 ng/mL, P = 0.008) and KL-6 (372.0 vs. 325.8 mu g/mL, P = 0.001). Lung cancer risk increased with SP-D (P-trend = 0.0003) and KL-6 levels (P-trend = 0.005). Compared with the lowest quartile, lung cancer risk was elevated among those with the highest quartiles of SP-D (OR = 1.87, 95% CI: 1.32-2.64) or KL-6 (OR = 1.58, 95% CI: 1.11-2.25). Among controls, participants with CXR scarring were more likely than those without scarring to have elevated levels of SP-D (quartile 4 vs. quartile 1: OR = 1.67, 95% CI: 1.04-2.70, P-trend = 0.05) but not of KL-6 (OR = 1.04, 95% CI: 0.64-1.68, P-trend = 0.99). Conclusion: Circulating levels of SP-D and KL-6 are associated with subsequent lung cancer risk. Impact: Our findings support a potential role for interstitial lung disease in lung cancer etiology or early detection, but additional research is needed. Cancer Epidemiol Biomarkers Prev; 20(10); 2262-72. (C) 2011 AACR.