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Cancer Res. 2014 Dec 15;74(24):7442-52. doi: 10.1158/0008-5472.CAN-14-1835. Epub 2014 Oct 21.

Plasma choline metabolites and colorectal cancer risk in the Women's Health Initiative Observational Study.

Author information

1
Division of Nutritional Sciences, Cornell University, Ithaca, New York.
2
Fred Hutchinson Cancer Research Center, Seattle, Washington. German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany. Huntsman Cancer Institute, Salt Lake City, Utah. mac379@cornell.edu neli.ulrich@hci.utah.edu.
3
Fred Hutchinson Cancer Research Center, Seattle, Washington.
4
Department of Foods and Nutrition, University of Georgia, Athens, Georgia.
5
Department of Nutritional Sciences, Rutgers University, New Brunswick, New Jersey. Department of Medical Pathology and Laboratory Medicine, University of California, Davis, California.
6
Department of Medical Pathology and Laboratory Medicine, University of California, Davis, California.
7
Department of Preventive Medicine, Stony Brook University School of Medicine, Stony Brook, New York.
8
Division of Nutritional Sciences, Cornell University, Ithaca, New York. mac379@cornell.edu neli.ulrich@hci.utah.edu.

Abstract

Few studies have examined associations between plasma choline metabolites and risk of colorectal cancer. Therefore, we investigated associations between plasma biomarkers of choline metabolism [choline, betaine, dimethylglycine, and trimethylamine N-oxide (TMAO)] and colorectal cancer risk among postmenopausal women in a case-control study nested within the Women's Health Initiative Observational Study. We selected 835 matched case-control pairs, and cases were further stratified by tumor site (proximal, distal, or rectal) and stage (local/regional or metastatic). Colorectal cancer was assessed by self-report and confirmed by medical records over the mean of 5.2 years of follow-up. Baseline plasma choline metabolites were measured by LC/MS-MS. In multivariable-adjusted conditional logistic regression models, plasma choline tended to be positively associated with rectal cancer risk [OR (95% confidence interval, CI)(highest vs. lowest quartile) = 2.44 (0.93-6.40); P trend = 0.08], whereas plasma betaine was inversely associated with colorectal cancer overall [0.68 (0.47-0.99); P trend = 0.01] and with local/regional tumors [0.64 (0.42-0.99); P trend = 0.009]. Notably, the plasma betaine:choline ratio was inversely associated with colorectal cancer overall [0.56 (0.39-0.82); P trend = 0.004] as well as with proximal [0.66 (0.41-1.06); P trend = 0.049], rectal [0.27 (0.10-0.78); P trend = 0.02], and local/regional [0.50 (0.33-0.76); P trend = 0.001] tumors. Finally, plasma TMAO, an oxidative derivative of choline produced by intestinal bacteria, was positively associated with rectal cancer [3.38 (1.25-9.16); P trend = 0.02] and with overall colorectal cancer risk among women with lower (vs. higher) plasma vitamin B12 levels (P interaction = 0.003). Collectively, these data suggest that alterations in choline metabolism, which may arise early in disease development, may be associated with higher risk of colorectal cancer. The positive association between plasma TMAO and colorectal cancer risk is consistent with an involvement of the gut microbiome in colorectal cancer pathogenesis.

PMID:
25336191
PMCID:
PMC4268282
DOI:
10.1158/0008-5472.CAN-14-1835
[Indexed for MEDLINE]
Free PMC Article

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