Assessment of Lung Cancer Risk on the Basis of a Biomarker Panel of Circulating Proteins

• Main Authors: Guida, F., Sun, N., Bantis, L.E., Muller, D.C., Li, P., Taguchi, A., Dhillon, D., Kundnani, D.L., Patel, N.J., Yan, Q., Byrnes, G., Moons, K.G.M., Tjønneland, A., Panico, S., Agnoli, C., Vineis, P., Palli, D., Bueno-De-Mesquita, B., Peeters, P.H., Agudo, A., Huerta, J.M., Dorronsoro, M., Barranco, M.R., Ardanaz, E., Travis, R.C., Byrne, K.S., Boeing, H., Steffen, A., Kaaks, R., Hüsing, A., Trichopoulou, A., Lagiou, P., La Vecchia, C., Severi, G., Boutron-Ruault, M.-C., Sandanger, T.M., Weiderpass, E., Nøst, T.H., Tsilidis, K., Riboli, E., Grankvist, K., Johansson, M., Goodman, G.E., Feng, Z., Brennan, P., Hanash, S.M.
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2018
• Subjects: Northern Sweden
• Online Access: https://pergamos.lib.uoa.gr/uoa/dl/object/uoadl:3085626

Importance: There is an urgent need to improve lung cancer risk assessment because current screening criteria miss a large proportion of cases. Objective: To investigate whether a lung cancer risk prediction model based on a panel of selected circulating protein biomarkers can outperform a traditional risk prediction model and current US screening criteria. Design, Setting, and Participants: Prediagnostic samples from 108 ever-smoking patients with lung cancer diagnosed within 1 year after blood collection and samples from 216 smoking-matched controls from the Carotene and Retinol Efficacy Trial (CARET) cohort were used to develop a biomarker risk score based on 4 proteins (cancer antigen 125 [CA125], carcinoembryonic antigen [CEA], cytokeratin-19 fragment [CYFRA 21-1], and the precursor form of surfactant protein B [Pro-SFTPB]). The biomarker score was subsequently validated blindly using absolute risk estimates among 63 ever-smoking patients with lung cancer diagnosed within 1 year after blood collection and 90 matched controls from 2 large European population-based cohorts, the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Northern Sweden Health and Disease Study (NSHDS). Main Outcomes and Measures: Model validity in discriminating between future lung cancer cases and controls. Discrimination estimates were weighted to reflect the background populations of EPIC and NSHDS validation studies (area under the receiver-operating characteristics curve [AUC], sensitivity, and specificity). Results: In the validation study of 63 ever-smoking patients with lung cancer and 90 matched controls (mean [SD] age, 57.7 [8.7] years; 68.6% men) from EPIC and NSHDS, an integrated risk prediction model that combined smoking exposure with the biomarker score yielded an AUC of 0.83 (95% CI, 0.76-0.90) compared with 0.73 (95% CI, 0.64-0.82) for a model based on smoking exposure alone (P =.003 for difference in AUC). At an overall specificity of 0.83, based on the US Preventive Services Task Force ...