Plasma Choline Metabolites and Colorectal Cancer Risk in the Women's Health Initiative Observational Study

Bae, Sajin; Ulrich, Cornelia M.; Neuhouser, Marian L.; Malysheva, Olga; Bailey, Lynn B.; Xiao, Liren; Brown, Elissa C.; Cushing‐Haugen, Kara L.; Zheng, Yingye; Cheng, Ting; Miller, Joshua W.; Green, Ralph; Lane, Dorothy S.; Beresford, Shirley A.A.; Caudill, Marie A.

doi:10.1158/0008-5472.can-14-1835

Cited by 205 publications

(165 citation statements)

References 52 publications

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“…the risk of reverse causation was reduced by the long follow-up time between baseline blood sampling and diagnosis of the colorectal cancer cases (median 8.2 years). the median follow-up times of the previously published studies were relatively short (median 3.6 and 5.2 years for ePic and WHi, respectively), 12,13 and concerns about potential reverse causality were expressed. 13 a longer follow-up is particularly advantageous in studies of folate and related metabolites, for investigation of possible dual effects in colorectal cancer prevention and progression.…”

Section: Discussionmentioning

confidence: 99%

“…notably, this is consistent with earlier studies. [12][13][14] absolute risk calculations in terms of marginal risk differences for high versus low plasma levels of betaine and methionine yielded estimated average reductions of colorectal cancer occurrence of approximately 200 cases per 100,000 individuals in the study cohort. given the population-based nature of the cohort, 16,17 the potential effects of higher methionine and betaine concentrations on colorectal cancer risk may be substantial.…”

Section: Discussionmentioning

confidence: 99%

“…these results were in line with the two previous prospective studies of circulating levels of the same one-carbon metabolites, 12,13 despite a considerably lower folate status in our study cohort. 7,12,19 there is no mandatory folate fortification of food products in Sweden, and the use of supplements and natural food folate intake is generally low in the northern Swedish population. 37 this might be expected to allow the discrimination of associations otherwise masked or compensated by higher folate status.…”

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confidence: 99%

“…4,7 a greater understanding of the relative contribution of components in the one-carbon metabolism, including methionine and factors in the choline oxidation pathway, to colorectal cancer risk may therefore provide new insight into the mechanistic role of onecarbon metabolism in carcinogenesis. 11 to the best of our knowledge, only two previous prospective studies of colorectal cancer, nested within the european Prospective investigation into cancer and nutrition (ePic) cohort and the Women's Health initiative (WHi), 12,13 and one cross-sectional study of colorectal adenoma, 14 have addressed the role of circulating one-carbon metabolites other than folate in colorectal cancer development. inverse risk associations for betaine and null results for choline were observed in all three studies, [12][13][14] and an inverse association to colorectal cancer for methionine was reported in the ePic study.…”

mentioning

confidence: 99%

“…11 to the best of our knowledge, only two previous prospective studies of colorectal cancer, nested within the european Prospective investigation into cancer and nutrition (ePic) cohort and the Women's Health initiative (WHi), 12,13 and one cross-sectional study of colorectal adenoma, 14 have addressed the role of circulating one-carbon metabolites other than folate in colorectal cancer development. inverse risk associations for betaine and null results for choline were observed in all three studies, [12][13][14] and an inverse association to colorectal cancer for methionine was reported in the ePic study. 13 the aim of this study was to investigate whether plasma concentrations of components of one-carbon metabolism, i.e., choline, betaine, dimethylglycine, sarcosine, and methionine, were related to colorectal cancer risk in a large, population-based, nested case-control study with long follow-up time.…”

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confidence: 99%

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Components of One-carbon Metabolism Other than Folate and Colorectal Cancer Risk

et al. 2016

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Background: Despite extensive study, the role of folate in colorectal cancer remains unclear. research has therefore begun to address the role of other elements of the folate-methionine metabolic cycles. this study investigated factors other than folate involved in one-carbon metabolism, i.e., choline, betaine, dimethylglycine, sarcosine, and methionine and relevant polymorphisms, in relation to the risk of colorectal cancer in a population with low intakes and circulating levels of folate. Methods: this was a prospective case-control study of 613 case subjects and 1,190 matched control subjects nested within the population-based northern Sweden Health and Disease Study. We estimated odds ratios (Or) by conditional logistic regression, and marginal risk differences with weighted maximum likelihood estimation using incidence data from the study cohort. Results: Higher plasma concentrations of methionine and betaine were associated with modest colorectal cancer risk reductions (Or [95% confidence interval {ci}] for highest versus lowest tertile: 0.76 [0.57, 0.99] and 0.72 [0.55, 0.94], respectively). estimated marginal risk differences corresponded to approximately 200 fewer colorectal cancer cases per 100,000 individuals on average. We observed no clear associations between choline, dimethylglycine, or sarcosine and colorectal cancer risk. the inverse association of methionine was modified by plasma folate concentrations (Or [95% ci] for highest/ lowest versus lowest/lowest tertile of plasma methionine/folate concentrations 0.39 [0.24, 0.64], P interaction = 0.06). Conclusions: in this population-based, nested case-control study with a long follow-up time from baseline to diagnosis (median: 8.2 years), higher plasma concentrations of methionine and betaine were associated with lower colorectal cancer risk.See Video abstract at http://links.lww.com/eDe/B83. (Epidemiology 2016;27: 787-796) O ne-carbon metabolism is an intracellular network involving the folate and methionine cycles, in which methyl groups and other one-carbon units are transferred to acceptor molecules ( Figure 1). a central role for one-carbon metabolism in cancer development is biologically plausible, as related nucleotide synthesis and methylation reactions including Dna methylation are vital for genome stability and function.the potential role of one-carbon metabolism in colorectal cancer development has been extensively studied, with most research to date focusing on folate. Diets rich in natural folates are associated with reduced risk of colorectal cancer. 1 However, a dual role of folate has been proposed, both preventing and promoting cancer, depending on the dose and timing of exposure. 2,3 Folate is not a one-carbon unit donor per se, but an enzymatic co-factor important for maintenance of the substrate flux in one-carbon metabolism. it might therefore be expected to stabilize the genome of normal mucosa, protecting against cancer, while accelerating the progression of precancerous or malignant lesions. 2 although evidence from animal...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Components of One-carbon Metabolism Other than Folate and Colorectal Cancer Risk

et al. 2016

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Role of the Gut Microbiota and Its Metabolites in Tumorigenesis or Development of Colorectal Cancer

Zhang

et al. 2023

Advanced Science

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Colorectal cancer (CRC) is the most common cancer of the digestive system with high mortality and morbidity rates. Gut microbiota is found in the intestines, especially the colorectum, and has structured crosstalk interactions with the host that affect several physiological processes. The gut microbiota include CRC‐promoting bacterial species, such as Fusobacterium nucleatum, Escherichia coli, and Bacteroides fragilis, and CRC‐protecting bacterial species, such as Clostridium butyricum, Streptococcus thermophilus, and Lacticaseibacillus paracasei, which along with other microorganisms, such as viruses and fungi, play critical roles in the development of CRC. Different bacterial features are identified in patients with early‐onset CRC, combined with different patterns between fecal and intratumoral microbiota. The gut microbiota may be beneficial in the diagnosis and treatment of CRC; some bacteria may serve as biomarkers while others as regulators of chemotherapy and immunotherapy. Furthermore, metabolites produced by the gut microbiota play essential roles in the crosstalk with CRC cells. Harmful metabolites include some primary bile acids and short‐chain fatty acids, whereas others, including ursodeoxycholic acid and butyrate, are beneficial and impede tumor development and progression. This review focuses on the gut microbiota and its metabolites, and their potential roles in the development, diagnosis, and treatment of CRC.

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Trimethylamine N‐Oxide Electrochemical Biosensor with a Chimeric Enzyme

et al. 2018

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For the first time, an enzyme-based electrochemical biosensor system for determination of trimethylamine N-oxide (TMAO) is described. It employs an active chimeric variant of TorA in combination with an enzymatically deoxygenating system and a low-potential mediator for effective regeneration of the enzyme and cathodic current generation. TMAO reductase (TorA) is a molybdoenzyme found in marine and most enterobacteria that specifically catalyzes the reduction of TMAO to trimethylamine (TMA). The chimeric TorA, named TorA-FDH, corresponds to the apoform of TorA from Escherichia coli reconstituted with the molybdenum cofactor from formate dehydrogenase (FDH). Each enzyme, TorA and TorA-FDH, was immobilized on the surface of a carbon electrode and protected with a dialysis membrane. The biosensor operates at an applied potential of À 0.8 V [vs. Ag/AgCl (1 M KCl)] under ambient air conditions thanks to an additional enzymatic O 2 -scavenger system. A comparison between the two enzymatic sensors revealed a much higher sensitivity for the biosensor with immobilized TorA-FDH. This biosensor exhibits a sensitivity of 14.16 nA/μM TMAO in a useful measuring range of 2-110 μM with a detection limit of LOD = 2.96 nM (S/N = 3), and was similar for TMAO in buffer and in spiked serum samples. With a response time of 16 � 2 s, the biosensor is stable over prolonged daily measurements (n = 20). This electrochemical biosensor provides suitable applications in detecting TMAO levels in human serum.It can also catalyze other N-oxide compounds, like 4-methyl [a] B.

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Plasma Choline Metabolites and Colorectal Cancer Risk in the Women's Health Initiative Observational Study

Cited by 205 publications

References 52 publications

Components of One-carbon Metabolism Other than Folate and Colorectal Cancer Risk

Components of One-carbon Metabolism Other than Folate and Colorectal Cancer Risk

Role of the Gut Microbiota and Its Metabolites in Tumorigenesis or Development of Colorectal Cancer

Trimethylamine N‐Oxide Electrochemical Biosensor with a Chimeric Enzyme

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