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Serum Trimethylamine N‐Oxide (TMAO), Diet, and Colorectal Cancer Risk
Author(s) -
Guertin Kristin A,
Graubard Barry I,
Goedert James J,
Li XinMin,
Hazen Stanley L,
Sinha Rashmi
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.lb271
Subject(s) - trimethylamine n oxide , colorectal cancer , carnitine , medicine , choline , odds ratio , quartile , gastroenterology , biomarker , endocrinology , cancer , confidence interval , trimethylamine , chemistry , biochemistry
Objective Choline and carnitine are two compounds that are found in human diets and can be metabolized to trimethylamine (TMA) and, ultimately, to Trimethylamine N‐Oxide (TMAO) by the gut microbiota. There is evidence that individuals with higher serum TMAO concentrations may have subclinical inflammation and greater risk of deleterious health outcomes, including heart disease. There is limited research on the potential role of TMAO in colorectal risk, and no studies that consider dietary intake of choline‐ and carnitine‐containing foods simultaneously with TMAO and colorectal cancer risk. We evaluated the association between serum TMAO and colorectal cancer risk (total, proximal, distal, and rectal colorectal cancers) in a nested case‐control study. Methods Within the Alpha‐Tocopherol Beta‐Carotene (ATBC) Study, a cohort of male smokers, we incidence‐density matched 644 incident colorectal cancer cases (median 14 years after baseline) and 644 controls. We selected baseline fasting serum samples and used liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) to measure TMAO and stable isotope dilution LC‐MS/MS to measure carnitine and choline. Spearman correlations describe the association between these serum biomarkers and the association between the biomarkers and self‐reported dietary intake of choline‐ and carnitine‐containing foods (e.g., meat, eggs). Logistic regression models estimate the adjusted odds ratios (OR) and 95% confidence intervals (CI) for colorectal cancer by quartile of each serum biomarker and, separately, by choline‐ and carnitine‐containing foods. Results Colorectal cancer risk was not associated with serum TMAO [OR highest vs. lowest quartile =1.20; 95% CI=0.86–1.68], carnitine [OR highest vs. lowest quartile =1.03; 95%CI=0.73–1.44], or dietary intake of choline‐ and carnitine‐containing foods. Individuals with higher serum choline had greater risk of colorectal cancer, with about a 3‐fold greater risk for the highest compared to lowest quartile in models adjusted for age, batch, and smoking [OR (95% CI)=3.38 (2.37–4.80); P‐trend<0.0001]; results were similarly robust for all anatomical subsites (P‐trend<0.0001 for proximal, distal, and rectal colon cancers). Conclusions This study provides strong evidence that alterations in choline metabolism, here investigated as higher serum choline concentrations, may be a marker of increased colorectal cancer risk. There was no evidence of an association between serum TMAO and risk of colorectal cancer. The strength of the associations between choline and colorectal cancer risk and the consistency of the risk estimates across all examined anatomical subsites strongly supports a role of altered choline metabolism in colorectal cancer pathogenesis. Support or Funding Information Intramural Research Program of the National Cancer Institute of the National Institutes of Health