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

Cancer research (2014-10-23)
Sajin Bae, Cornelia M Ulrich, Marian L Neuhouser, Olga Malysheva, Lynn B Bailey, Liren Xiao, Elissa C Brown, Kara L Cushing-Haugen, Yingye Zheng, Ting-Yuan David Cheng, Joshua W Miller, Ralph Green, Dorothy S Lane, Shirley A A Beresford, Marie A Caudill
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Betaine solution, 5 M, PCR Reagent
Sigma-Aldrich
Vitamin B12, ≥98%
Sigma-Aldrich
Choline chloride, ≥99%
Sigma-Aldrich
Betaine, ≥98% (perchloric acid titration)
Sigma-Aldrich
Choline chloride, ≥98%
Supelco
Cyanocobalamin, pharmaceutical secondary standard, certified reference material
Sigma-Aldrich
Pyridoxal 5′-phosphate hydrate, ≥98%
Sigma-Aldrich
Betaine, BioUltra, ≥99.0% (NT)
Sigma-Aldrich
Betaine hydrochloride, ≥99%
Sigma-Aldrich
Vitamin B12, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for plant cell culture, ≥98%
Sigma-Aldrich
Trimethylamine N-oxide, 95%
Sigma-Aldrich
Choline chloride, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥98%
Supelco
Cyanocobalamin (B12), analytical standard
Sigma-Aldrich
Pyridoxal 5′-phosphate monohydrate, ≥97.0% (NT)
Sigma-Aldrich
Cyanocobalamin, meets USP testing specifications
Supelco
Choline chloride, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Pyridoxal 5′-phosphate hydrate, powder, BioReagent, suitable for cell culture
Sigma-Aldrich
Choline chloride, BioUltra, ≥99.0% (AT)
Cyanocobalamin, European Pharmacopoeia (EP) Reference Standard
USP
Choline chloride, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Cyanocobalamin, tested according to Ph. Eur.
Cyanocobalamin, British Pharmacopoeia (BP) Assay Standard