title: Urinary Metabolite Risk Biomarkers of Lung Cancer: A Prospective Cohort Study.
abstract: Lung cancer is a major health burden causing 160,000 and 1.6 million deaths annually in the United States and worldwide, respectively.
  
  
  
  While seeking to identify stable and reproducible biomarkers in noninvasively collected biofluids, we assessed whether previously identified metabolite urinary lung cancer biomarkers, creatine riboside (CR), N-acetylneuraminic acid (NANA), cortisol sulfate, and indeterminate metabolite 561+, were elevated in the urines of subjects prior to lung cancer diagnosis in a well-characterized prospective Southern Community Cohort Study (SCCS). Urine was examined from 178 patients and 351 nondiseased controls, confirming that one of four metabolites was associated with lung cancer risk in the overall case-control set, whereas two metabolites were associated with lung cancer risk in European-Americans.
  
  
  
  OR of lung cancer associated with elevated CR levels, and adjusted for smoking and other potential confounders, was 2.0 [95% confidence interval (CI), 1.2-3.4; P= 0.01]. In European-Americans, both CR and NANA were significantly associated with lung cancer risk (OR = 5.3; 95% CI, 1.6-17.6; P= 0.006 and OR=3.5; 95% CI, 1.5-8.4; P= 0.004, respectively). However, race itself did not significantly modify the associations. ROC analysis showed that adding CR and NANA to a model containing previously established lung cancer risk factors led to a significantly improved classifier (P= 0.01). Increasing urinary levels of CR and NANA displayed a positive association with increasing tumor size, strengthening a previously established link to altered tumor metabolism.
  
  
  
  These replicated results provide evidence that identified urinary metabolite biomarkers have a potential utility as noninvasive, clinical screening tools for early diagnosis of lung cancer. Cancer Epidemiol Biomarkers Prev; 25(6); 978-86. ©2016 AACR.
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
authors.forename: Majda
authors.initials: M
authors.lastname: Haznadar
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Qiuyin
authors.initials: Q
authors.lastname: Cai
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
authors.forename: Kristopher W
authors.initials: KW
authors.lastname: Krausz
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
authors.forename: Elise D
authors.initials: ED
authors.lastname: Bowman
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
authors.forename: Ezra
authors.initials: E
authors.lastname: Margono
authors.affiliation: Nippon Medical School, Tokyo, Japan.
authors.forename: Rintaro
authors.initials: R
authors.lastname: Noro
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Thompson
authors.affiliation: Biomedical Informatics, The Ohio State University College of Medicine, Columbus, Ohio.
authors.forename: Ewy A
authors.initials: EA
authors.lastname: Mathé
authors.affiliation: International Epidemiology Institute, Rockville, Maryland.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Munro
authors.affiliation: International Epidemiology Institute, Rockville, Maryland.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Steinwandel
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Gonzalez
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee. International Epidemiology Institute, Rockville, Maryland. Curtis_Harris@nih.gov blotw@iei.us.
authors.forename: William J
authors.initials: WJ
authors.lastname: Blot
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland. Curtis_Harris@nih.gov blotw@iei.us.
authors.forename: Curtis C
authors.initials: CC
authors.lastname: Harris
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000652:urine*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000652:urine*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011446:Prospective Studies; D012372:ROC Curve; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor