Research: GUERTIN and COLLEAGUES,

Listed in Issue 253

Abstract

GUERTIN and COLLEAGUES, 1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland. kguertin@virginia.edu ; 2. Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, Virginia; 3. Department of Cellular & Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio; 4. Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland; 5. Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio studied the relationship between serum concentrations of  Trimethylamine N-oxide (TMAO) and its biomarker precursors (choline, carnitine, and betaine) and incident colorectal cancer risk in a nested case-control study of male smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study.

Background

Trimethylamine N-oxide (TMAO), a choline-derived metabolite produced by gut microbiota, and its biomarker precursors have not been adequately evaluated in relation to colorectal cancer risk.

Methodology

We investigated the relationship between serum concentrations of TMAO and its biomarker precursors (choline, carnitine, and betaine) and incident colorectal cancer risk in a nested case-control study of male smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. We measured biomarker concentrations in baseline fasting serum samples from 644 incident colorectal cancer cases and 644 controls using LC/MS-MS. Logistic regression models estimated the ORs and 95% confidence interval (CI) for colorectal cancer by quartile (Q) of serum TMAO, choline, carnitine, and betaine concentrations.

Results

Men with higher serum choline at ATBC baseline had approximately 3-fold greater risk of developing colorectal cancer over the ensuing (median ± IQR) 14 ± 10 years (in fully adjusted models, Q4 vs. Q1, OR, 3.22; 95% CI, 2.24-4.61; Ptrend < 0.0001). The prognostic value of serum choline for prediction of incident colorectal cancer was similarly robust for proximal, distal, and rectal colon cancers (all P < 0.0001). The association between serum TMAO, carnitine, or betaine and colorectal cancer risk was not statistically significant (P = 0.25, 0.71, and 0.61, respectively).

Conclusion

Higher serum choline concentration (but not TMAO, carnitine, or betaine) was associated with increased risk of colorectal cancer. Impact: Serum choline levels showed strong prognostic value for prediction of incident colorectal cancer risk across all anatomical subsites, suggesting a role of altered choline metabolism in colorectal cancer pathogenesis.

References

Guertin KA1,2, Li XS3, Graubard BI4, Albanes D4, Weinstein SJ4, Goedert JJ4, Wang Z3, Hazen SL3,5, Sinha R4. Serum Trimethylamine N-oxide, Carnitine, Choline, and Betaine in Relation to Colorectal Cancer Risk in the Alpha Tocopherol, Beta Carotene Cancer Prevention Study. Cancer Epidemiol Biomarkers Prev.;26(6): 945-952. Jun 2017. doi: 10.1158/1055-9965.EPI-16-0948. Epub Jan 11 2017.

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