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      Urinary Metabolite Risk Biomarkers of Lung Cancer: A Prospective Cohort Study

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          Abstract

          <div class="section"> <a class="named-anchor" id="S1"> <!-- named anchor --> </a> <h5 class="section-title" id="d738507e238">Background</h5> <p id="P1">Lung cancer is a major health burden causing 160,000 and 1.6 million deaths annually in the United State and worldwide, respectively. </p> </div><div class="section"> <a class="named-anchor" id="S2"> <!-- named anchor --> </a> <h5 class="section-title" id="d738507e243">Methods</h5> <p id="P2">Seeking to identify stable and reproducible biomarkers in non-invasively collected biofluids, we assessed whether previously identified metabolite urinary lung cancer biomarkers, creatine riboside (CR), <i>N</i>-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 non-diseased 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. </p> </div><div class="section"> <a class="named-anchor" id="S3"> <!-- named anchor --> </a> <h5 class="section-title" id="d738507e251">Results</h5> <p id="P3">Odds ratio of lung cancer associated with elevated CR levels, and adjusted for smoking and other potential confounders, was 2.0 (95%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. Receiver Operating Characteristic (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. </p> </div><div class="section"> <a class="named-anchor" id="S4"> <!-- named anchor --> </a> <h5 class="section-title" id="d738507e256">Conclusion and Impact</h5> <p id="P4">These replicated results provide evidence that identified urinary metabolite biomarkers have a potential utility as non-invasive, clinical screening tools for early diagnosis of lung cancer. </p> </div>

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          Author and article information

          Journal
          Cancer Epidemiology Biomarkers & Prevention
          Cancer Epidemiology Biomarkers & Prevention
          American Association for Cancer Research (AACR)
          1055-9965
          1538-7755
          May 31 2016
          March 24 2016
          : 25
          : 6
          : 978-986
          Article
          10.1158/1055-9965.EPI-15-1191
          4891298
          27013655
          2fab0f71-d26a-4395-9b03-cd20b0c9d9f5
          © 2016
          History

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