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.
journal_name
Carcinogenesisjournal_title
Carcinogenesisauthors
Goedert JJ,Sampson JN,Moore SC,Xiao Q,Xiong X,Hayes RB,Ahn J,Shi J,Sinha Rdoi
10.1093/carcin/bgu131subject
Has Abstractpub_date
2014-09-01 00:00:00pages
2089-96issue
9eissn
0143-3334issn
1460-2180pii
bgu131journal_volume
35pub_type
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