Folate status, genomic DNA hypomethylation, and risk of colorectal adenoma and cancer: a case control study

Pufulete, Maria; Al-Ghnaniem, Reyad; Leather, Andrew J M; Appleby, Paul N.; Gout, Sally; Terry, Catherine; Emery, Peter W.; Sanders, Tom

doi:10.1016/s0016-5085(03)00279-8

Cited by 247 publications

(213 citation statements)

References 45 publications

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“…The mean value for plasma homocysteine (10.570.26 mmol/l) is well below the 14.0 mmol/l, usually recognized as the high-risk cut-off value for hyperhomocysteinemia and related diseases. Vitamin B12 mean plasma concentration (203.773.03 pmol/l) is well above the cut-off range for vitamin B12 deficiency (Institute of Medicine, 2000) and our results match values published by Pufulete et al (2003) in patients diagnosed with colorectal cancer.…”

Section: Resultssupporting

confidence: 90%

“…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%

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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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Section: Resultssupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

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

et al. 2007

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“…The laboratory methods used to analyse serum and erythrocyte folate concentrations, plasma homocysteine, genomic DNA methylation and gene polymorphisms have been described in detail elsewhere (Pufulete et al, 2003). Genomic DNA methylation was determined in colonic mucosa using an in vitro methyl acceptance assay (Balaghi and Wagner, 1993).…”

Section: Laboratory Methodsmentioning

confidence: 99%

“…A recent study suggested that DNA hypomethylation in normal-appearing colonic mucosa is associated with low folate status and increased risk of colorectal neoplasia (Pufulete et al, 2003). However, no studies have investigated the relationship between DNA methylation in colonic mucosa and folate status in subjects without colorectal adenoma or cancer.…”

mentioning

confidence: 99%

Influence of folate status on genomic DNA methylation in colonic mucosa of subjects without colorectal adenoma or cancer

et al. 2005

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DNA hypomethylation may increase the risk of colorectal cancer. The main aim of this study was to assess the influence of folate status (serum and erythrocyte folate and plasma homocysteine concentrations) on DNA methylation. Methylenetetrahydrofolate reductase (MTHFR 677C-T and 1298A-C), methionine synthase (MS 2756A-G) and cystathionine synthase (CBS 844ins68) polymorphisms were measured to account for potential confounding effects on folate status and DNA methylation. A total of 68 subjects (33 men and 35 women, 36 -78 years) free from colorectal polyps or cancer were recruited in a cross-sectional study. Tissue biopsies were obtained at colonoscopy for the determination of DNA methylation in colonic mucosa using an in vitro radiolabelled methyl acceptance assay. Serum and erythrocyte folate were inversely correlated with plasma homocysteine (r ¼ À0.573, Po0.001 and r ¼ À0.307, P ¼ 0.01 respectively) and DNA hypomethylation in colonic mucosa (r ¼ À0.311, P ¼ 0.01 and r ¼ À0.356, P ¼ 0.03). After adjusting for gender, age, body mass index, smoking and genotype, there were weak negative associations between serum and erythrocyte folate and colonic DNA hypomethylation (P ¼ 0.07 and P ¼ 0.08, respectively).

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“…DNA methylation is critical for regulating gene expression [1]. Methionine synthase is a vitamin B 12 -dependent enzyme, which catalyzes the remethylation of homocysteine to methionine and the concurrent demethylation of 5-methyltetrahydrofolate to tetrahydrofolate.…”

Section: Introductionmentioning

confidence: 99%

Role of polymorphism of methyltetrahydrofolate-homocysteine methyltransferase (MTR) A2756G and breast cancer risk

Hosseini¹

2013

pjp

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Breast cancer (BC) is one of the most common causes of death among women, and second in Iran. The objectives of this study were to determine the frequency of methyltetrahydrofolate-homocysteine methyltransferase (MTR) 2756 gene polymorphism in patients with breast cancer. For the first time, we evaluated these polymorphisms and effects on the breast cancer risk association in an Iranian sporadic populationbased case-control study of 282 breast cancer cases and 310 controls using a PCR-RFLP-based assay. Analyses of affected and controls show that homozygote genotype MTR 2756 AA has the highest frequency in both groups (33.3 in patients). Genotype MTR 2756 GG was the highest risk factor in our population [AG/GG odds ratio, 0.329 (95% CI: 0.146-0.741) p = 0.006, AA/AG, OR, 2.316, 95% CI: 1.509-3.555, p = 0.001, AA/GG odds ratio, 0.761 (95% CI: 0.363-1.595) p = 0.297]. There was a significant association of breast cancer risk with MTR 2756 GG and AA polymorphism.

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Folate status, genomic DNA hypomethylation, and risk of colorectal adenoma and cancer: a case control study

Cited by 247 publications

References 45 publications

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

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

Influence of folate status on genomic DNA methylation in colonic mucosa of subjects without colorectal adenoma or cancer

Role of polymorphism of methyltetrahydrofolate-homocysteine methyltransferase (MTR) A2756G and breast cancer risk

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