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

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.

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  • Authors+Show Affiliations

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    Division of Nutritional Sciences, Cornell University, Ithaca, New York.

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    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.

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    Fred Hutchinson Cancer Research Center, Seattle, Washington.

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    Division of Nutritional Sciences, Cornell University, Ithaca, New York.

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    Department of Foods and Nutrition, University of Georgia, Athens, Georgia.

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    Fred Hutchinson Cancer Research Center, Seattle, Washington.

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    Fred Hutchinson Cancer Research Center, Seattle, Washington.

    ,

    Fred Hutchinson Cancer Research Center, Seattle, Washington.

    ,

    Fred Hutchinson Cancer Research Center, Seattle, Washington.

    ,

    Fred Hutchinson Cancer Research Center, Seattle, Washington.

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    Department of Nutritional Sciences, Rutgers University, New Brunswick, New Jersey. Department of Medical Pathology and Laboratory Medicine, University of California, Davis, California.

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    Department of Medical Pathology and Laboratory Medicine, University of California, Davis, California.

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    Department of Preventive Medicine, Stony Brook University School of Medicine, Stony Brook, New York.

    ,

    Fred Hutchinson Cancer Research Center, Seattle, Washington.

    Division of Nutritional Sciences, Cornell University, Ithaca, New York. mac379@cornell.edu neli.ulrich@hci.utah.edu.

    Source

    Cancer research 74:24 2014 Dec 15 pg 7442-52

    MeSH

    Aged
    Betaine
    Choline
    Colorectal Neoplasms
    Female
    Humans
    Methylamines
    Middle Aged
    Risk Factors
    Women's Health

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    25336191

    Citation

    Bae, Sajin, et al. "Plasma Choline Metabolites and Colorectal Cancer Risk in the Women's Health Initiative Observational Study." Cancer Research, vol. 74, no. 24, 2014, pp. 7442-52.
    Bae S, Ulrich CM, Neuhouser ML, et al. Plasma choline metabolites and colorectal cancer risk in the Women's Health Initiative Observational Study. Cancer Res. 2014;74(24):7442-52.
    Bae, S., Ulrich, C. M., Neuhouser, M. L., Malysheva, O., Bailey, L. B., Xiao, L., ... Caudill, M. A. (2014). Plasma choline metabolites and colorectal cancer risk in the Women's Health Initiative Observational Study. Cancer Research, 74(24), pp. 7442-52. doi:10.1158/0008-5472.CAN-14-1835.
    Bae S, et al. Plasma Choline Metabolites and Colorectal Cancer Risk in the Women's Health Initiative Observational Study. Cancer Res. 2014 Dec 15;74(24):7442-52. PubMed PMID: 25336191.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Plasma choline metabolites and colorectal cancer risk in the Women's Health Initiative Observational Study. AU - Bae,Sajin, AU - Ulrich,Cornelia M, AU - Neuhouser,Marian L, AU - Malysheva,Olga, AU - Bailey,Lynn B, AU - Xiao,Liren, AU - Brown,Elissa C, AU - Cushing-Haugen,Kara L, AU - Zheng,Yingye, AU - Cheng,Ting-Yuan David, AU - Miller,Joshua W, AU - Green,Ralph, AU - Lane,Dorothy S, AU - Beresford,Shirley A A, AU - Caudill,Marie A, Y1 - 2014/10/21/ PY - 2014/10/23/entrez PY - 2014/10/23/pubmed PY - 2015/2/11/medline SP - 7442 EP - 52 JF - Cancer research JO - Cancer Res. VL - 74 IS - 24 N2 - 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. SN - 1538-7445 UR - https://www.unboundmedicine.com/medline/citation/25336191/Plasma_choline_metabolites_and_colorectal_cancer_risk_in_the_Women's_Health_Initiative_Observational_Study_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=25336191 DB - PRIME DP - Unbound Medicine ER -