title: Prediagnostic serum levels of inflammatory biomarkers are correlated with future development of lung and esophageal cancer.
abstract: This study tests the hypothesis that prediagnostic serum levels of 20 cancer-associated inflammatory biomarkers correlate directly with future development of head and neck, esophageal, and lung cancers in a high-risk prospective cohort. This is a nested case-control pilot study of subjects enrolled in the Golestan Cohort Study, an ongoing epidemiologic project assessing cancer trends in Golestan, Iran. We measured a panel of 20 21 cytokines, chemokines, and inflammatory molecules using Luminex technology in serum samples collected 2 or more years before cancer diagnosis in 78 aerodigestive cancer cases and 81 controls. Data was analyzed using Wilcoxon rank sum test, odds ratios, receiver operating characteristic areas of discrimination, and multivariate analysis. Biomarkers were profoundly and globally elevated in future esophageal and lung cancer patients compared to controls. Odds ratios were significant for association between several biomarkers and future development of esophageal cancer, including interleukin-1Rα (IL-1Ra; 35.9), interferon α2 (IFN-a2; 34.0), fibroblast growth factor-2 (FGF-2; 17.4), and granulocyte/macrophage colony-stimulating factor (GM-CSF; 17.4). The same pattern was observed among future lung cancer cases for G-CSF (27.7), GM-CSF (13.3), and tumor necrosis factor-α (TNF-a; 8.6). By contrast, the majority of biomarkers studied showed no significant correlation with future head and neck cancer development. This study provides the first direct evidence that multiple inflammatory biomarkers are coordinately elevated in future lung and esophageal cancer patients 2 or more years before cancer diagnosis.
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Brieze R
authors.initials: BR
authors.lastname: Keeley
authors.forename: Farhad
authors.initials: F
authors.lastname: Islami
authors.forename: Akram
authors.initials: A
authors.lastname: Pourshams
authors.forename: Hossein
authors.initials: H
authors.lastname: Poustchi
authors.forename: Jamie S
authors.initials: JS
authors.lastname: Pak
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.forename: Hooman
authors.initials: H
authors.lastname: Khademi
authors.forename: Eric M
authors.initials: EM
authors.lastname: Genden
authors.forename: Christian C
authors.initials: CC
authors.lastname: Abnet
authors.forename: Sanford M
authors.initials: SM
authors.lastname: Dawsey
authors.forename: Paolo
authors.initials: P
authors.lastname: Boffetta
authors.forename: Reza
authors.initials: R
authors.lastname: Malekzadeh
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Sikora
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D063646:Carcinogenesis / Q000378:metabolism; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000097:blood* / Q000175:diagnosis; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D008175:Lung Neoplasms / Q000097:blood* / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012372:ROC Curve
chemical_list: D014408:Biomarkers, Tumor; D018836:Inflammation Mediators
keywords: Aerodigestive cancer; esophageal squamous cell carcinoma; head and neck squamous cell carcinoma; lung cancer; serum inflammatory biomarker