DNA methylation as an intermediate biomarker in colorectal cancer

Cravo, Marília; Fidalgo, Paula; Pereira, António Dias; Gouveia-Oliveira, A; Chaves, Paula; Selhub, Jacob; Mason, Joel B.; Mira, F. Costa; Leitão, C. Nobre

doi:10.1097/00008469-199411000-00004

Cited by 157 publications

(87 citation statements)

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“…Folate deficiency has not been shown unequivocally to induce genomic or site-specific DNA hypomethylation but is still considered as a possible mechanism. Cravo et al 53,54 observed that folate supplementation significantly reversed genomic DNA hypomethylation of the colonic mucosa. Kim et al 55 reported that DNA methylation underwent improvement with folate supplementation.…”

Section: Discussionmentioning

confidence: 99%

Intake of dietary folate vitamers and risk of colorectal carcinoma

Konings

Goldbohm

Brants

et al. 2002

Cancer

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BACKGROUNDSeveral studies have reported inverse associations between folate intake and colorectal carcinoma risk. Few were prospective studies and none evaluated the association between the intake of individual folate vitamers and colorectal carcinoma risk.METHODSThe aim of the current study was to investigate the relationship between dietary folate intake and the risk of colorectal carcinoma in a large prospective cohort study in The Netherlands comprising 120,852 men and women aged 55–69 years. After 7.3 years of follow‐up, 760 colon and 411 rectal carcinoma cases were available for analysis. Data processing and analysis used the case–cohort approach. A new Dutch database was used to estimate intakes of total and individual folate vitamers.RESULTSAnalyses adjusted for age, energy intake, family history of colorectal carcinoma, alcohol, vitamin C, iron, and dietary fiber intake yielded an inverse association between colon carcinoma risk and total dietary folate intake (rate ratio [RR]highest vs. lowest quintile, men: 0.73; 95% confidence interval [CI], 0.46–1.17, P trend = 0.03; women: 0.68; 95% CI, 0.39–1.20, P trend = 0.18). An inverse association between rectal carcinoma and total dietary folate intake was found only among men (RR highest vs. lowest quintile, men: 0.66; 95% CI, 0.35–1.21, P trend = 0.03). Analyses showed no clear difference in colorectal carcinoma risk associated with intake of different folate vitamers.CONCLUSIONSDietary folate intake was related inversely to colon and male rectal carcinoma risk. Cancer 2002;95:1421–33. © 2002 American Cancer Society.DOI 10.1002/cncr.10866

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Section: Discussionmentioning

confidence: 99%

Intake of dietary folate vitamers and risk of colorectal carcinoma

Konings

Goldbohm

Brants

et al. 2002

Cancer

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“…Homocysteine is thus an accurate inverse indicator of folate status (Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, 1999). Low folate status can result in increased chromosome instability, DNA damage, impaired repair, aberrant DNA methylation and point mutations (Cravo et al, 1994;Fenech et al, 1997;Kim, 1999). These initiate colon carcinogenesis Folic acid (Kim et al, 1996;Newmark et al, 2001;Konings et al, 2002) (2) Insulin resistance/plasma insulin, free fatty acids and triacylglycerol (McKeown-Eyssen, 1994;Giovannucci, 1995;Kim, 1998) Dietary factors including a hypercaloric diet with refined sugars, increased saturated fat, and reduced n-3 fatty acids, together with reduced energy expenditure, increase the accumulation of energy substrates in the body and lead to insulin resistance (Storlien et al, 1991;Tran et al, 1996Tran et al, , 2003Koohestani et al, 1998;Bruce et al, 2000;Kaaks et al, 2000).…”

Section: Study Protocolmentioning

confidence: 99%

A pilot randomised controlled trial to reduce colorectal cancer risk markers associated with B-vitamin deficiency, insulin resistance and colonic inflammation

Cirocco

Giacca

et al. 2005

Br J Cancer

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Colorectal cancer risk is associated with biochemical markers for B-vitamin deficiency, insulin resistance and colonic inflammation, suggesting that these three conditions are each involved in colon carcinogenesis. We expected that dietary supplements of folic acid, n-3 fatty acids and calcium would reduce the markers and thus possibly cancer risk. We therefore randomised 98 participants, with previous colonic polyps or intramucosal carcinomas, to a combined treatment of supplementary folic acid, fish oil and calcium carbonate, or placebos for 28 days. Blood and faecal samples were obtained prior to and at the conclusion of the intervention and analysed for plasma folate, homocysteine, insulin, free fatty acids, triglycerides and faecal calprotectin. In addition, plasma vitamin B 12 , thiamin, glucose and C-reactive protein were assessed. Our supplemental strategy modestly affected some of the biomarkers associated with folate metabolism and insulin resistance, but had no effect on those associated with colonic inflammation. This pilot study demonstrates the feasibility and practicality of clinical trials aimed at reducing diet-related biochemical risk markers for colon cancer. We suggest that long-term intervention studies with tumour-related end points should be undertaken when the intervention agents used are found effective in short-term biochemical risk marker trials.

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“…In colorectal cancer, genomic DNA hypomethylation has been reported in tumour tissue (Goelz et al, 1985;Cravo et al, 1994) and there are also reports of decreased DNA methylation in normal appearing colonic mucosa from individuals with colorectal cancer or adenoma (Cravo et al, 1994;Pufulete et al, 2003). However, very few studies have attempted to study changes in methylation intermediates, either systemic or tissue specific, in humans diagnosed with colorectal cancer.…”

Section: Resultsmentioning

confidence: 99%

Folate status and S-adenosylmethionine/S-adenosylhomocysteine ratio in colorectal adenocarcinoma in humans

et al. 2007

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Objectives: This study reports the influence of colorectal neoplasia on methylation intermediates and folate concentrations in human colonic mucosa, as well as systemic measures of folate status, to examine biomarkers and possible mechanisms of folaterelated carcinogenesis. Subjects: A total of 47 patients were selected from those previously diagnosed with adenocarcinoma of the colorectum undergoing surgery. For each individual, we obtained a biopsy of the adenocarcinoma and a biopsy of normal appearing mucosa, to perform an intra-individual comparison. Results: The 'methylation' ratio (S-adenosylmethionine/S-adenosylhomocysteine (SAH)) was lower in pathological tissue vs normal mucosa (P ¼ 0.08), mainly due to a much higher SAH concentration (Po0.005). Colonic folate concentration was significantly diminished in malignant tissue (Po0.0001). Plasma homocysteine concentration was within the normal to high range, and folate and vitamin B12 plasma concentrations were within the low to normal range as compared with normative values. Conclusion: Our results contribute to the hypothesis that altered DNA methylation and methyl metabolism is associated with colorectal neoplasia.

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DNA methylation as an intermediate biomarker in colorectal cancer

Cited by 157 publications

References 0 publications

Intake of dietary folate vitamers and risk of colorectal carcinoma

Intake of dietary folate vitamers and risk of colorectal carcinoma

A pilot randomised controlled trial to reduce colorectal cancer risk markers associated with B-vitamin deficiency, insulin resistance and colonic inflammation

Folate status and S-adenosylmethionine/S-adenosylhomocysteine ratio in colorectal adenocarcinoma in humans

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