The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index.
Plasma Choline Metabolites and Colorectal Cancer Risk in the Women's Health Initiative Observational Study
Open accessPublished version of a preprint
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. Cancer Res; 74(24); 7442–52. ©2014 AACR.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The Women's Health Initiative and the alpha-tocopherol, beta-carotene cancer prevention observational studies reported that alterations in choline metabolism and plasma TMAO concentrations were predicted risk factors for colorectal cancer (7,83).”
From Trimethylamine N -Oxide, the Microbiome, and Heart and Kidney Disease (2017) · cites this paper as [7]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Recent human studies have established that the levels of TMAO in serum are positively correlated with impaired renal function, colorectal cancer, and cardiovascular disease (CVD) (8, 10, 17, 18).”
From Intestinal Microbiota Composition Modulates Choline Bioavailability from Diet and Accumulation of the Proatherogenic Metabolite Trimethylamine- N -Oxide (2015) · cites this paper as [18]
Experimental — accuracy not yet measuredIn the citing paper
“In support of this hypothesis, the association between plasma level of TMAO and risk of CRC was restricted to patients with low plasma levels of vitamin B12.151”
From Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer (2020) · cites this paper as [151]
In the citing paper
“Some,147, 148 but not all,149–151 prospective studies have associated higher dietary and plasma levels of choline with increased risk of colorectal neoplasia.”
From Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer (2020) · cites this paper as [151]
In the citing paper
“Recent human studies have established that the levels of TMAO in serum are positively correlated with impaired renal function, colorectal cancer, and cardiovascular disease (CVD) (8, 10, 17, 18).”
From Intestinal Microbiota Composition Modulates Choline Bioavailability from Diet and Accumulation of the Proatherogenic Metabolite Trimethylamine- N -Oxide (2015) · cites this paper as [18]
In the citing paper
“Recent human studies have established that the levels of TMAO in serum are positively correlated with impaired renal function, colorectal cancer, and cardiovascular disease (CVD) (8, 10, 17, 18).”
From Intestinal Microbiota Composition Modulates Choline Bioavailability from Diet and Accumulation of the Proatherogenic Metabolite Trimethylamine- N -Oxide (2015) · cites this paper as [18]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
An obesity-associated gut microbiome with increased capacity for energy harvest
Turnbaugh, P. J., Ley, R. E., Mahowald, M. A., Magrini, V., Mardis, E. R., & Gordon, J. I. (2006) · Nature · doi:10.1038/nature05414 · Cited by 12,444
Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease
Wang, Z., Klipfell, E., Bennett, B. J., Koeth, R., Levison, B. S., DuGar, B., Feldstein, A. E., Britt, E. B., Fu, X., Chung, Y.-M., et al. (2011) · Nature · doi:10.1038/nature09922 · Cited by 5,597
Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis
Koeth, R. A., Wang, Z., Levison, B. S., Buffa, J. A., Org, E., Sheehy, B. T., Britt, E. B., Fu, X., Wu, Y., Li, L., et al. (2013) · Nature Medicine · doi:10.1038/nm.3145 · Cited by 4,386
Design of the Women’s Health Initiative Clinical Trial and Observational Study
The Women’s Health Initiative Study Group (1998) · Controlled Clinical Trials · doi:10.1016/s0197-2456(97)00078-0 · Cited by 2,580
Colorectal Cancer Epidemiology: Incidence, Mortality, Survival, and Risk Factors
Haggar, F. A., & Boushey, R. P. (2009) · Clinics in Colon and Rectal Surgery · doi:10.1055/s-0029-1242458 · Cited by 2,018
Bacteria as vitamin suppliers to their host: A gut microbiota perspective
LeBlanc, J. G., Milani, C., de Giori, G. S., Sesma, F., van Sinderen, D., & Ventura, M. (2013) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2012.08.005 · Cited by 1,613 · cited 1×
“Certain groups of intestinal bacteria can synthesize (45, 46) and consume (47, 48) vitamin B12, 291 which may impact the vitamin B12 requirement/status of the host.”
Folate and DNA Methylation: A Review of Molecular Mechanisms and the Evidence for Folate's Role
Crider, K. S., Yang, T. P., Berry, R. J., & Bailey, L. B. (2012) · Advances in Nutrition · doi:10.3945/an.111.000992 · Cited by 1,055
Self-citationDumas, M.-E., Barton, R. H., Toye, A., Cloarec, O., Blancher, C., Rothwell, A., Fearnside, J., Tatoud, R., Blanc, V., Lindon, J. C., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601056103 · Cited by 1,042
Choline metabolism in malignant transformation
Glunde, K., Bhujwalla, Z. M., & Ronen, S. M. (2011) · Nature reviews. Cancer · doi:10.1038/nrc3162 · Cited by 826
Outcomes ascertainment and adjudication methods in the women's health initiative
Curb, J. D., McTiernan, A., Heckbert, S. R., Kooperberg, C. L., Stanford, J. L., Nevitt, M. C., Johnson, K., Proulx-Burns, L., Pastore, L. M., Criqui, M. H., et al. (2003) · Annals of Epidemiology · doi:10.1016/s1047-2797(03)00048-6 · Cited by 700
Research works printed but not linked: 1
- US Food and Drug Administration, 1996, Food standards: amendment of standards of identity for enriched grain products to require addition of folic acid. Final Rule. 21 CFR Parts 136, 137, and 139, Fed Regist, 61, 8781
Cited by
Sorted by citations
Thomas, A. M., Manghi, P., Asnicar, F., Pasolli, E., Armanini, F., Zolfo, M., Beghini, F., Manara, S., Karcher, N., Pozzi, C., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0405-7 · Cited by 1,030
Self-citationInfluence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer
Song, M., Chan, A. T., & Sun, J. (2020) · Gastroenterology · doi:10.1053/j.gastro.2019.06.048 · Cited by 752
Romano, K. A., Vivas, E. I., Amador-Noguez, D., & Rey, F. E. (2015) · mBio · doi:10.1128/mbio.02481-14 · Cited by 777
Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health
Parker, A., Fonseca, S., & Carding, S. R. (2019) · Gut Microbes · doi:10.1080/19490976.2019.1638722 · Cited by 745
Trimethylamine N -Oxide, the Microbiome, and Heart and Kidney Disease
Zeisel, S. H., & Warrier, M. (2017) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071816-064732 · Cited by 475
Metadata
- Authors
- Bae, S., Ulrich, C. M., Neuhouser, M. L., Malysheva, O., Bailey, L. B., Xiao, L., Brown, E. C., Cushing-Haugen, K. L., Zheng, Y., Cheng, T.-Y. D., Miller, J. W., Green, R., Lane, D. S., Beresford, S. A. A., & Caudill, M. A.
- Affiliations
- Cornell University (US)
- German Cancer Research Center (DE)
- Fred Hutch Cancer Center (US)
- University of Georgia (US)
- 2Fred Hutchinson Cancer Research Center, Seattle, Washington.
- Rutgers, The State University of New Jersey (US)
- University of California, Davis (US)
- Stony Brook School (US)
- Corresponding author
- Ulrich, Cornelia M.
- Caudill, Marie A.
- ORCID
- Venue
- Cancer Research
- Published
- 2014-12-14
- Volume
- 74
- Issue
- 24
- Pages
- 7442-7452
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC4268282
- OpenAlex
- W2092436074
- Cited by
- 253
- References
- 56
- Citations by year
- 2026: 9 · 2025: 17 · 2024: 27 · 2023: 34 · 2022: 23 · 2021: 34 · 2020: 24 · 2019: 20 · 2018: 19 · 2017: 17 · 2016: 16 · 2015: 13
- FWCI
- 15.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- U.S. Department of Health and Human Services
- National Institutes of Health (HHSN268201100004C, n01wh22110-38-0-0, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, N01 WH022110)
- National Institute on Aging (HHSN-271-2011-00004C,)
- National Heart, Lung, and Blood Institute (HHSN2682011-00001I, HHSN2682011-00002I, HHSN2682011‐00004I, HHSN268201100046C, HHSN2682011-00003I)
- National Cancer Institute (R01CA120523)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Keywords
- colorectal cancer risk, choline metabolism, plasma choline, betaine, dimethylglycine, trimethylamine N-oxide, rectal cancer, postmenopausal women, vitamin B12, tumor location, tumor stage, plasma biomarkers, Women's Health Initiative Observational Study, gut microbiota, oxidative stress, inflammation
- MeSH terms
- Aged, Betaine, Choline, Female, Humans, Methylamines, Middle Aged, Risk Factors, Colorectal Neoplasms, Women's Health
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
