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ISSN-2155-9929

Journal of Molecular Biomarkers & Diagnosis
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Research Article

Aberrantly Methylated Gene Marker Levels in Stool: Effects of Demographic, Exposure, Body Mass, and Other Patient Characteristics

David A Ahlquist1*, William R Taylor1, Tracy C Yab1, Mary E Devens1, Douglas W Mahoney2, Lisa A Boardman1, Steven N Thibodeau3, Hongzhi Zou4, Michael J Domanico4, Barry M Berger4 and Graham P Lidgard4

1Division of Gastroenterology and Hepatology, Mayo Clinic, USA

2Department of Biostatistics, Mayo Clinic, USA

3Department of Laboratory Medicine and Pathology, Mayo Clinic, USA

4Exact Sciences Corporation, Madison WI, USA

*Corresponding Author:
David A Ahlquist, MD
Division of Gastroenterology and Hepatology
Mayo Clinic, Rochester, MN 55905, USA
Fax: 507-266-0350
E-mail: [email protected]

Received date: August 02, 2012; Accepted date: September 01, 2012; Published date: September 04, 2012

Citation: Ahlquist DA, Taylor WR, Yab TC, Devens ME, Mahoney DW, et al. (2012) Aberrantly Methylated Gene Marker Levels in Stool: Effects of Demographic, Exposure, Body Mass, and Other Patient Characteristics. J Mol Biomark Diagn 3:133. doi:10.4172/2155-9929.1000133

Copyright: © 2012 Ahlquist DA, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Abstract

Background: Selected aberrantly methylated genes represent sensitive candidate stool markers for colorectal cancer (CRC) screening. We assessed the impact of demographic, exposure, body mass, and other patient variables on stool levels of highly informative methylated gene markers — BMP3, NDRG4, vimentin, and TFPI2. Methods: We studied freezer-archived stools from 500 patients with normal colonoscopy (median age 64 (range 44-85); 53% women). On supernatants from thawed aliquots, target gene sequences were purified by hybrid capture; bisulfite treated, and assayed using the analytically-sensitive QuARTS method (quantitative allele-specific real-time target and signal amplification). The reference human gene β-actin was assayed along with the 4 methylated genes. Results: Only age significantly influenced all methylated marker levels in stool (p<0.0001 for each). The relative increase per standard deviation of age was greatest with TFPI2 at 49.4% and least with BMP3 at only 0.21%; levels of β-actin did not change across age. Other demographic variables (sex, race, and residence), exposures (smoking, alcohol, or analgesic use), family or personal history of colorectal neoplasia, body mass, and diabetes mellitus had no effect on methylated marker levels. Conclusions: Although stool levels of candidate methylated markers increase with age to variable extents, most common clinical covariates have no effect. Impact: These findings have important implications on CRC screening compliance, as patients using a stool test that incorporates these markers would not have to make life-style or medication adjustments. Furthermore, age effect can be mitigated by adjustment of cut-off levels based on age or by selection of markers least influenced by age.

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