Circulating Pro-Surfactant Protein B as a Risk Biomarker for Lung Cancer

Background: Our prior studies of lung cancer suggested that a novel biomarker (pro- surfactant protein B or pro-SFTPB) might serve as a predictive marker for this disease. We aimed to determine the potential utility of pro-SFTPB for distinguishing lung cancer cases from matched controls as a risk marker. Methods: Study subjects were drawn from the longitudinal Physicians' Health Study (PHS). Cases (n = 188) included individuals who were cancer-free at study enrollment but developed lung cancer during follow-up. Controls (n = 337) were subjects who did not develop lung cancer. Cases and controls were matched on date of study enrollment, age at enrollment, and smoking status and amount. Baseline plasma samples drawn at enrollment were analyzed for pro-SFTPB using ELISA to detect differences in protein expression levels for cases and controls. Results: Pro-SFTPB-non-detectable status was significantly associated with lung cancer risk (OR = 5.88, 95% CI 1.24, 27.48). Among subjects with detectable levels of the protein, increasing plasma concentration of pro-SFTPB was associated with higher lung cancer risk (OR = 1.41 per unit increase in log pro-SFTPB, 95% CI 1.08, 1.84). Conclusion: These results suggest a non-linear, J- shaped association between plasma pro-SFTPB levels and lung cancer risk, with both non-detectable and higher levels of the marker being associated with lung cancer. Impact: These results show promise of a risk marker that could contribute to predicting risk for lung cancer development and to narrowing the high risk population for low-dose computed tomography (LDCT) screening.