This work was supported by the Intramural Research Program of the National Cancer Institute, US National Institute of Health (NIH) (project ZIACP101231 to M.T.L.); by the NIH grants R01ES032547-01, R01CA269919-01 and 1U01CA290479-01 to L.B.A. as well as by L.B.A.’s Packard Fellowship for Science and Engineering. The research performed in L.B.A.’s laboratory was also supported by UC San Diego Sanford Stem Cell Institute. The funders had no roles in study design, data collection and analysis, decision to publish or preparation of the manuscript. The M.D.-G. fellowship, within the “Generación D” initiative, Red.es, Ministerio para la Transformación Digital y de la Función Pública, for talent attraction (C005/24-ED CV1), is funded by the European Union NextGenerationEU funds, through PRTR. The computational analyses reported in this manuscript have used the NIH high-performance Biowulf Cluster and the Triton Shared Computing Cluster at the San Diego Supercomputer Center of UC San Diego. We thank the study participants; P. Kraft for reading manuscript and comments; and the staff at Westat for their assistance in collecting samples and corresponding clinical data. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organization. This research was supported by the Intramural Research Program of the NIH. The contributions of the NIH authors were made as part of their official duties as NIH federal employees, are in compliance with agency policy requirements, and are considered works of the United States Government. However, the findings and conclusions presented in this paper are those of the authors and do not necessarily reflect the views of the NIH or the US Department of Health and Human Services. We want to acknowledge the patients and the INCLIVA Biobank (PT17/0015/0049) integrated in the Spanish National Biobanks Network and in the Valencian Biobanking Network for their collaboration. This study was supported by the Health and Medical Research Fund of Hong Kong SAR, HMRF 03142856. The related studies of Taiwan site were supported by grants from the Ministry of Health and Welfare, Taiwan DOH97-TD-G-111-026 (C.A.H.), DOH98-TD-G-111-015 (C.A.H.), DOH99-TD-G-111-028 (C.A.H.); DOH97-TD-G-111-029 (C.Y.C.), DOH98-TD-G-111-018 (C.Y.C.), DOH99-TD-G-111-015 (C.Y.C.), DOH97-TD-G-111-028(I.S.C.), DOH98-TD-G-111-017(I.S.C.), DOH99-TD-G-111-014(I.S.C.), and the Ministry of Science and Technology, Taiwan MOST109-2740-B-400-002 (C.A.H.), MOST110-2740-B-400-002 (C.A.H.), MOST111-2740-B-400-002 (C.A.H.). This work has been supported in part by the Tissue Core at the H. Lee Moffitt Cancer Center & Research Institute, a comprehensive cancer center designated by the National Cancer Institute and funded in part by a Moffitt Cancer Center Support Grant (no. P30-CA076292). And, in part, by NIH (NCI) grant # U01CA209414 to the Boston Lung Cancer Survival Study of the Dana-Farber/ Harvard Cancer Center (D.C.C.). The authors would like to thank the team at the IUCPQ site of the Quebec Respiratory Health Network Biobank of the FRQS for their valuable assistance, and would like to thank the staff at Harvard University, Yale University, Roswell Park Cancer Institute and Roswell PI, Instituto Nacional de Cancerologia, Nice University Hospital Centre (Nice UHC) - University Côte d’Azur and the Nice Biobank CRB, Toronto University Health Network, and Mayo Clinic for their assistance providing samples and corresponding clinical data.