Abstract
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 folate-related 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=0.08), mainly due to a much higher SAH concentration (P<0.005). Colonic folate concentration was significantly diminished in malignant tissue (P<0.0001). 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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Abbreviations
- SAH=:
-
S-adenosylhomocysteine
- SAM=:
-
S-adenosylmethionine
References
Cantoni GL (1985). The role of S-adenosylhomocysteine in the biological utilization of S-adenosylmethionine. Prog Clin Biol Res 198, 47–65.
Castro R, Rivera I, Struys EA, Jansen EEW, Ravasco P, Camilo ME et al. (2003). Increased homocysteine and S-adenosylhomocysteine concentrations and DNA hypomethylation in vascular disease. Clin Chem 49, 1292–1296.
Caudill MA, Wang JC, Melnyk S, Pogribny IP, Jernigan S, Collins MD et al. (2001). Intracellular S-adenosylhomocysteine concentrations predict global DNA hypomethylation in tissues of methyl-deficient cystathionine β-synthase heterozygous mice. J Nutr 131, 2811–2818.
Choi SW, Mason JB (2000). Folate and carcinogenesis: an integrated scheme. J Nutr 130, 129–132.
Choi SW, Mason JB (2002). Folate status: effect on pathways of colorectal carcinogenesis. J Nutr 132, 2413S–2418S.
Cravo M, Fidalgo P, Pereira AD, Gouveia-Oliveira A, Chaves P, Selhub J et al. (1994). DNA methylation as an intermediate biomarker in colorectal cancer: modulation by folic acid supplementation. Eur J Cancer Prev 3, 473–479.
de Meer K, Finglas PM, Molloy A, Pietrzik K, Powers HJ, Jägerstad M et al. (2006). Position paper: goals for folate and related vitamins in Europe and the developing world. Eur J Clin Nutr 60, 287–294.
Giovannucci E (2002). Epidemiological studies of folate and colorectal neoplasia: a review. J Nutr 132, 2350S–2355S.
Goelz SE, Vogelstein B, Hamilton SR, Feinberg AP (1985). Hypomethylation of DNA from benign and malignant human colon neoplasms. Science 228, 187–190.
Hoffman DR, Cornatzer WE, Duerre JA (1979). Relationship between tissue levels of S-adenosylmethionine, S-adenosylhomocysteine, and transmethylation reactions. Can J Biochem 57, 56–65.
Hoffman DR, Marion DW, Cornatzer WE, Duerre JA (1980). S-adenosylmethionine and S-adenosylhomocysteine metabolism in isolated liver. J Biol Chem 22, 10822–10827.
Institute of Medicine (2000). Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. National Academy Press: Washington, DC.
James SJ, Melnyk S, Pogribna M, Pogribny IP, Caudill MA (2002). Elevation in S-adenosylhomocysteine and DNA hypomethylation: potential epigenetic mechanism for homocysteine-related pathology. J Nutr 132, 2361S–2366S.
Kim YI (1999). Folate and carcinogenesis: evidence, mechanisms, and implications. J Nutr Biochem 10, 66–88.
Kim YI (2004). Folate and DNA methylation: a mechanistic link between folate deficiency and colorectal cancer? Cancer Epidemiol Bio Prev 13, 511–519.
Kim YI, Fawaz K, Knox T, Lee YM, Norton R, Arora S et al. (1998). Colonic mucosal concentrations of folate correlate well with blood measurements of folate status in persons with colorectal polyps. Am J Clin Nutr 68, 866–872.
Laird PW, Jaenisch R (1996). The role of DNA methylation in cancer genetics and epigenetics. Annu Rev Genet 30, 441–464.
Meenan J, ÓHallinan E, Scott J, Weir DG (1997). Epithelial cell folate depletion occurs in neoplastic but not adjacent normal colon mucosa. Gastroenterology 112, 1163–1168.
Pufulete M, Al-Ghnaniem R, Leather AJM, Appleby P, Gout S, Terry C et al. (2003). Folate status, genomic DNA hypomethylation, and risk of colorectal adenoma and cancer: a case control study. Gastroenterology 124, 1240–1248.
Stempak JM, Sohn KJ, Chiang EP, Shane B, Kim YI (2005). Cell and stage of transformation – specific effects of folate deficiency on methionine cycle intermediates and DNA methylation in an in vitro model. Carcinogenesis 26, 981–990.
Varela-Moreiras G (2003). Folate deficiency. In: Vaquero P, García-Arias T, Carbajal A, Sánchez-Muñiz FJ (eds). Bioavailability of Micronutrients and Minor Dietary Compounds Metabolic and Technological Aspects pp 68–81. Research Signpost: Kerala, India.
Wainfan E, Poirier LA (1992). Methyl groups in carcinogenesis: effects on DNA methylation and gene expression. Cancer Res 52, 2071S–2077S.
Yi P, Melnyk KS, Pogribna M, Pogribny IP, Hine RJ, James SJ (2000). Increase in plasma homocysteine associated with parallel increases in plasma S-adenosylhomocysteine and lymphocyte DNA hypomethylation. J Biol Chem 275, 29318–29323.
Acknowledgements
This research was granted by the Regional Government, Comunidad de Madrid Research Plan, Spain (contract no. 08.1/0041.2/98). We thank the fellows from Servicio de Cirugía general y de Aparato Digestivo from Hospital Fundación Jiménez Díaz (Madrid, Spain) for their collaboration in patient recruitment, surgery and sample collection. We also acknowledge the Vitamin Metabolism Laboratory, from the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University (Boston, MA, USA), for their technical assistance in folate determinations.
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Alonso-Aperte, E., González, M., Póo-Prieto, R. et al. Folate status and S-adenosylmethionine/S-adenosylhomocysteine ratio in colorectal adenocarcinoma in humans. Eur J Clin Nutr 62, 295–298 (2008). https://doi.org/10.1038/sj.ejcn.1602722
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DOI: https://doi.org/10.1038/sj.ejcn.1602722
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