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Carcinogenesis. 2014 Sep;35(9):2089-96. doi: 10.1093/carcin/bgu131. Epub 2014 Jul 18.

Fecal metabolomics: assay performance and association with colorectal cancer.

Author information

1
Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Bethesda, MD 20892-9704, USA, Information Management Services, 6110 Executive Boulevard, Rockville, MD 20852, USA and Division of Epidemiology, Department of Population Health, New York University School of Medicine, 650 First Avenue, #518, New York, NY 10016, USA goedertj@mail.nih.gov.
2
Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Bethesda, MD 20892-9704, USA, Information Management Services, 6110 Executive Boulevard, Rockville, MD 20852, USA and Division of Epidemiology, Department of Population Health, New York University School of Medicine, 650 First Avenue, #518, New York, NY 10016, USA.
3
Information Management Services, 6110 Executive Boulevard, Rockville, MD 20852, USA and.
4
Division of Epidemiology, Department of Population Health, New York University School of Medicine, 650 First Avenue, #518, New York, NY 10016, USA.

Abstract

Metabolomic analysis of feces may provide insights on colorectal cancer (CRC) if assay performance is satisfactory. In lyophilized feces from 48 CRC cases, 102 matched controls, and 48 masked quality control specimens, 1043 small molecules were detected with a commercial platform. Assay reproducibility was good for 527 metabolites [technical intraclass correlation coefficient (ICC) >0.7 in quality control specimens], but reproducibility in 6-month paired specimens was lower for the majority of metabolites (within-subject ICC ≤0.5). In the CRC cases and controls, significant differences (false discovery rate ≤0.10) were found for 41 of 1043 fecal metabolites. Direct cancer association was found with three fecal heme-related molecules [covariate-adjusted 90th versus 10th percentile odds ratio (OR) = 17-345], 18 peptides/amino acids (OR = 3-14), palmitoyl-sphingomyelin (OR = 14), mandelate (OR = 3) and p-hydroxy-benzaldehyde (OR = 4). Conversely, cancer association was inverse with acetaminophen metabolites (OR <0.1), tocopherols (OR = 0.3), sitostanol (OR = 0.2), 3-dehydrocarnitine (OR = 0.4), pterin (OR = 0.3), conjugated-linoleate-18-2N7 (OR = 0.2), N-2-furoyl-glycine (OR = 0.3) and p-aminobenzoate (PABA, OR = 0.2). Correlations suggested an independent role for palmitoyl-sphingomyelin and a central role for PABA (which was stable over 6 months, within-subject ICC 0.67) modulated by p-hydroxy-benzaldehyde. Power calculations based on ICCs indicate that only 45% of metabolites with a true relative risk 5.0 would be found in prospectively collected, prediagnostic specimens from 500 cases and 500 controls. Thus, because fecal metabolites vary over time, very large studies will be needed to reliably detect associations of many metabolites that potentially contribute to CRC.

PMID:
25037050
PMCID:
PMC4146421
DOI:
10.1093/carcin/bgu131
[Indexed for MEDLINE]
Free PMC Article

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