JSM 2004 - Toronto

Abstract #302139

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Activity Number: 264
Type: Topic Contributed
Date/Time: Tuesday, August 10, 2004 : 2:00 PM to 3:50 PM
Sponsor: Biometrics Section
Abstract - #302139
Title: The Use of Mediation Models to Identify and Validate Biomarkers
Author(s): John Kittelson*+ and Patrick Blatchford
Companies: University of Colorado Health Sciences Center and University of Colorado Health Sciences Center
Address: Preventive Medicine and Biometrics, Denver, CO, 80262,
Keywords: biomarker ; mediation model ; lung cancer
Abstract:

Survival rates in lung cancer patients are low because patients have disseminated disease at the time of diagnosis. Biomarkers are needed for early detection, and a major effort in lung cancer research is to identify and validate biomarkers. A very large number of candidate biomarkers are available from biochemical, cellular, and genetic measurements (e.g., DNA microarrays) on bronchial biopsy tissue and sputum samples. The standard approach to identifying biomarkers is to evaluate their expression in subjects with and without lung cancer using measures such as sensitivity and specificity. When evaluating many biomarkers, there is an elevated false positive rate. We discuss the use of mediation models to identify biomarkers that mediate the relationship between smoking and lung cancer. We show that this approach reduces the risk of falsely positive biomarkers. We discuss the implications of this approach to study design, and describe how smokers, nonsmokers, cancer cases, and controls should be selected to support this analysis. The methods are illustrated using biomarkers from bronchoscopy tissue specimens collected as part of the Colorado Lung SPORE cohort.

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