The NYU Lung Cancer Biomarker Center CVC has recruited 1143 high-risk smokers (SCREENING COHORT) for the early detection of lung cancer. We have evaluated 1047 study subjects in our R/0 LUNG CANCER COHORT in collaboration with Harvey Pass, MD and the Division of Thoracic Surgery. Questionnaires, blood (100ml), spirometry, sputum, and CT-scans are obtained. 52% of the SCREENING COHORT had non-calcified nodules (NCN) with 3771 CT-Scans obtained to assess growth rates. 22 thoracic neoplasms were diagnosed with 18 lung adenocarcinomas. Biomarker collaborations with D, Sidransky Johns Hopkins) identified a panel of genes with promoter hypermethylations in plasma from lung cancer patients. Consistent with this finding, we noted increased plasma S- adenosylmethionine, a key intermediate in the methylation pathway, in lung cancer patients compared to high-risk smokers with NCN. Using set aside funds, we showed a 29-gene expression pattern in PBMC that separated lung cancer from high-risk controls with L, Showe (Wistar, UPenn), M-s Tang and colleagues demonstrated DNA adducts occurred at hot spot mutation sites in p53 and K-ras, and that poor repair contributed to adduct persistence. Exhaled breath predicted lung cancer with high AUC using combinations of alkanes measured in GC/MS. Our research plan is to expand our CVC with 300 new high-risk smokers, 1000 follow-up NCNs, and >250 lung cancers. We will evaluate NCN by CT- scans for early detection. We will determine risk for lung cancer among high-risk smokers by measuring blood acrolein DNA adducts and PBMC DNA repair capacity. We will develop a phase 3 validation case control study of 200 lung cancer cases and 200 matched controls and a phase 4 validation cohorts study of 600 high-risk smokers with >40 incident lung cancers. We will evaluate serum for tumor-associated antigens, auto-antibodies, gene expression patterns in PBMC and pathway control by microRNAs. Importantly, we will cross validate biomarker panels in the same prospective high risk smoker cohorts.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZCA1-SRLB-3 (M1))
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Krueger, Karl E
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New York University
Internal Medicine/Medicine
Schools of Medicine
New York
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