Biomarkers Related to One-Carbon Metabolism as Potential Risk Factors for Distal Colorectal Adenomas

Vogel, Stefan de; Schneede, Jörn; Ueland, Per Magne; Vollset, Stein Emil; Meyer, Klaus; Fredriksen, Åse; Midttun, Øivind; Bjørge, Tone; Kampman, Ellen; Bretthauer, Michael; Hoff, Geir

doi:10.1158/1055-9965.epi-11-0359

Cited by 32 publications

(32 citation statements)

References 48 publications

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“…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%

“…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.…”

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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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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

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

et al. 2016

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“…In humans, the prospective Health Professionals Follow-up Study found no association with dietary choline or betaine intakes and CRC risk, even when stratifying choline by its metabolic derivatives (Lee et al 2010 ). However, in the Norwegian Colorectal Cancer Prevention Trial, the occurrence of high-risk distal colorectal adenomas was inversely associated with plasma betaine concentrations but not with choline (de Vogel et al 2011a ). Interestingly, in the Nurses Health Study, dietary choline was positively associated, yet betaine was inversely associated with risk of colorectal adenoma when comparing the highest quintile of concentrations to the lowest (Cho et al 2007a ).…”

Section: Colorectal Cancermentioning

confidence: 96%

One-Carbon Metabolism Nutrients and Epigenetics: A Mechanistic Link Between Aberrant One-Carbon Metabolism and Cancer Risk?

Masih

Plumptre

Kim

2014

Molecular Mechanisms and Physiology of Disease

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In relation to the genome, investigation of the epigenome is emerging as an equal, if not more infl uential factor in modulating human health and disease. Since epigenetic modifi cations are gradual in onset and potentially reversible, determining factors that modulate the epigenome is critical for possible preventive and therapeutic interventions. The development and progression of cancer is mechanistically linked to a number of epigenetic changes, including global DNA hypomethylation and genespecifi c CpG promoter DNA hypermethylation. Environmental factors, including diet, have been shown to affect cancer risk, via epigenetic and non-epigenetic mechanisms. In this regard, one-carbon nutrients are prototypic dietary factors that may modulate cancer risk via epigenetic mechanisms. This chapter will discuss the role of nutrients involved in one-carbon metabolism and their effect on cancer risk via epigenetic modifi cations with a particular focus on DNA methylation.

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“…Apart from the folates, some [87,88], though not all [89], epidemiological studies that have examined the issue suggest a protective effect of other nutrients linked to one-carbon metabolism against colorectal cancer, including methionine and betaine. Further studies to determine whether such potentially beneficial effects are associated with consistent epigenetic patterns in the colorectal mucosa would be valuable.…”

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confidence: 99%

The effect of diet on the intestinal epigenome

Johnson

Belshaw

2014

Epigenomics

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The colorectal mucosal epithelium is composed of rapidly proliferating crypt cells derived by clonal expansion from stem cells. The aging human colorectal mucosa develops aberrant patterns of DNA methylation that may contribute to its increasing vulnerability to cancer. Various types of evidence suggest that age-dependent loss of global methylation, together with hypermethylation of CpG islands associated with cancer-related genes, may be influenced by nutritional and metabolic factors. Folates are essential for the maintenance of normal DNA methylation, and folate metabolism is known to modify epigenetic mechanisms under experimental conditions. Human intervention trials and cross-sectional studies suggest a role for folates and other nutritional and metabolic factors as determinants of colorectal mucosal DNA methylation. Future studies should focus on the possibility that folic acid fortification may exert unforeseen effects on the human gastrointestinal epigenome. Naturally occurring DNA methyltransferase inhibitors in plant foods may be useful for the manipulation of epigenetic profiles in health and disease.

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Biomarkers Related to One-Carbon Metabolism as Potential Risk Factors for Distal Colorectal Adenomas

Cited by 32 publications

References 48 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

One-Carbon Metabolism Nutrients and Epigenetics: A Mechanistic Link Between Aberrant One-Carbon Metabolism and Cancer Risk?

The effect of diet on the intestinal epigenome

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