Skip to main content
Erschienen in: Journal of Inherited Metabolic Disease 1/2011

01.02.2011 | Homocysteine and B-Vitamin Metabolism

Folate and cancer: how DNA damage, repair and methylation impact on colon carcinogenesis

verfasst von: Susan J. Duthie

Erschienen in: Journal of Inherited Metabolic Disease | Ausgabe 1/2011

Einloggen, um Zugang zu erhalten

Abstract

Inappropriate diet may contribute to one third of cancer deaths. Folates, a group of water-soluble B vitamins present in high concentrations in green, leafy vegetables, maintain DNA stability through their ability to donate one-carbon units for cellular metabolism. Folate deficiency has been implicated in the development of several cancers, including cancer of the colorectum, breast, ovary, pancreas, brain, lung and cervix. Generally, data from the majority of human studies suggest that people who habitually consume the highest level of folate, or with the highest blood folate concentrations, have a significantly reduced risk of developing colon polyps or cancer. However, an entirely protective role for folate against carcinogenesis has been questioned, and recent data indicate that an excessive intake of synthetic folic acid (from high-dose supplements or fortified foods) may increase human cancers by accelerating growth of precancerous lesions. Nonetheless, on balance, evidence from the majority of human studies indicates that dietary folate is genoprotective against colon cancer. Suboptimal folate status in humans is widespread. Folate maintains genomic stability by regulating DNA biosynthesis, repair and methylation. Folate deficiency induces and accelerates carcinogenesis by perturbing each of these processes. This review presents recent evidence describing how these mechanisms act, and interact, to modify colon cancer risk.
Literatur
Zurück zum Zitat Arasaradam RP, Commane DM, Bradburn D et al (2008) A review of dietary factors and its influence on DNA methylation in colorectal carcinogenesis. Epigenetics 3:193–198CrossRef Arasaradam RP, Commane DM, Bradburn D et al (2008) A review of dietary factors and its influence on DNA methylation in colorectal carcinogenesis. Epigenetics 3:193–198CrossRef
Zurück zum Zitat Bagley P, Selhub J (1998) A common mutation in the methylenetetrahydrofolate reductase gene is associated with an accumulation of formylated tetrahydrofolates in red blood cells. Proc Natl Acad Sci USA 95:13217–13220CrossRefPubMed Bagley P, Selhub J (1998) A common mutation in the methylenetetrahydrofolate reductase gene is associated with an accumulation of formylated tetrahydrofolates in red blood cells. Proc Natl Acad Sci USA 95:13217–13220CrossRefPubMed
Zurück zum Zitat Balaghi M, Wagner C (1993) DNA methylation in folate deficiency: use of CpG methylase. Biochem Biophys Res Commun 193:1184–1190CrossRefPubMed Balaghi M, Wagner C (1993) DNA methylation in folate deficiency: use of CpG methylase. Biochem Biophys Res Commun 193:1184–1190CrossRefPubMed
Zurück zum Zitat Basten GP, Duthie SJ, Pirie L et al (2006) Sensitivity of markers of DNA stability and DNA repair activity to folate supplementation in healthy volunteers. Brit J Cancer 94:1942–1947CrossRefPubMed Basten GP, Duthie SJ, Pirie L et al (2006) Sensitivity of markers of DNA stability and DNA repair activity to folate supplementation in healthy volunteers. Brit J Cancer 94:1942–1947CrossRefPubMed
Zurück zum Zitat Beetstra S, Thomas P, Salisbury C et al (2005) Folic acid deficiency increases chromosomal instability, chromosome 21 aneuploidy and sensitivity to radiation-induced micronuclei. Mutat Res 578:317–326PubMed Beetstra S, Thomas P, Salisbury C et al (2005) Folic acid deficiency increases chromosomal instability, chromosome 21 aneuploidy and sensitivity to radiation-induced micronuclei. Mutat Res 578:317–326PubMed
Zurück zum Zitat Bigler J, Ulrich CM, Kawashima T et al (2006) Polymorphisms in hOGG1, XRCC1 and XRCC3 as risk factors for colorectal polyps. Proc Am Assoc Cancer Res 47:2051 Bigler J, Ulrich CM, Kawashima T et al (2006) Polymorphisms in hOGG1, XRCC1 and XRCC3 as risk factors for colorectal polyps. Proc Am Assoc Cancer Res 47:2051
Zurück zum Zitat Billson HA, Harrison KL, Lees NP et al (2009) Dietary variables associated with DNA N7-methylguanine and O6-alkylguanine DNA-alkyltransferase activity in human colorectal mucosa. Carcinogenesis 30:615–620CrossRefPubMed Billson HA, Harrison KL, Lees NP et al (2009) Dietary variables associated with DNA N7-methylguanine and O6-alkylguanine DNA-alkyltransferase activity in human colorectal mucosa. Carcinogenesis 30:615–620CrossRefPubMed
Zurück zum Zitat Blount BC, Ames BN (1994) Analysis of uracil in DNA by gas chromatography-mass spectometry. Anal Biochem 219:195–200CrossRefPubMed Blount BC, Ames BN (1994) Analysis of uracil in DNA by gas chromatography-mass spectometry. Anal Biochem 219:195–200CrossRefPubMed
Zurück zum Zitat Blount BC, Mack MM, Wehr CM et al (1997) Folate deficiency causes uracil misincorporation into human DNA and chromosomal breakage; implications for cancer and neuronal damage. Proc Natl Acad Sci USA 94:3290–3295CrossRefPubMed Blount BC, Mack MM, Wehr CM et al (1997) Folate deficiency causes uracil misincorporation into human DNA and chromosomal breakage; implications for cancer and neuronal damage. Proc Natl Acad Sci USA 94:3290–3295CrossRefPubMed
Zurück zum Zitat Bonaa KH, Njolstad I, Ueland PM et al (2006) NORVIT trial investigators. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 354:1578–1588CrossRefPubMed Bonaa KH, Njolstad I, Ueland PM et al (2006) NORVIT trial investigators. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 354:1578–1588CrossRefPubMed
Zurück zum Zitat Branda RF, LaFayette AR, O’Neill JP et al (1997) Effect of folate deficiency on mutations at the hprt locus in Chinese hamster ovary cells exposed to monofunctional alkylating agents. Cancer Res 57:2586–2588PubMed Branda RF, LaFayette AR, O’Neill JP et al (1997) Effect of folate deficiency on mutations at the hprt locus in Chinese hamster ovary cells exposed to monofunctional alkylating agents. Cancer Res 57:2586–2588PubMed
Zurück zum Zitat Branda RF, O’Neill JP, Brooks EM et al (2007) The effect of dietary folic acid deficiency on the cytotoxic and mutagenic responses to methyl methanesulfonate in wild type and in 30 methyladenine DNA glycosylase-deficient Aag null mice. Mutat Res 615:12–17PubMed Branda RF, O’Neill JP, Brooks EM et al (2007) The effect of dietary folic acid deficiency on the cytotoxic and mutagenic responses to methyl methanesulfonate in wild type and in 30 methyladenine DNA glycosylase-deficient Aag null mice. Mutat Res 615:12–17PubMed
Zurück zum Zitat Chen J, Giovannucci E, Kelsey K et al (1996) A methylenetetrahydrofolate reductase polymorphism and the risk of colorectal cancer. Cancer Res 56:4862–4864PubMed Chen J, Giovannucci E, Kelsey K et al (1996) A methylenetetrahydrofolate reductase polymorphism and the risk of colorectal cancer. Cancer Res 56:4862–4864PubMed
Zurück zum Zitat Choi S-W, Kim Y-I, Weitzel JN, Mason JB (1998) Folate depletion impairs DNA excision repair in the colon of the rat. Gut 43:93–99CrossRefPubMed Choi S-W, Kim Y-I, Weitzel JN, Mason JB (1998) Folate depletion impairs DNA excision repair in the colon of the rat. Gut 43:93–99CrossRefPubMed
Zurück zum Zitat Choi S-W, Stern LL, Dzialo HM et al (1999) A common polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene decreases genomic DNA methylation, but does not reduce DNA strand breaks, p53 methylation or uracil misincorporation: implications for colorectal carcinogenesis. Gastroenterol 116:G1707, abstract Choi S-W, Stern LL, Dzialo HM et al (1999) A common polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene decreases genomic DNA methylation, but does not reduce DNA strand breaks, p53 methylation or uracil misincorporation: implications for colorectal carcinogenesis. Gastroenterol 116:G1707, abstract
Zurück zum Zitat Christmann M, Tomicic MT, Rood WP, Kaina B (2003) Mechanisms of human DNA repair: an update. Toxicology 193:3–34CrossRefPubMed Christmann M, Tomicic MT, Rood WP, Kaina B (2003) Mechanisms of human DNA repair: an update. Toxicology 193:3–34CrossRefPubMed
Zurück zum Zitat Cole BF, Baron JA, Sandler RS et al (2007) Folic acid for the prevention of colorectal adenomas-a randomized clinical trial. JAMA 297:2351–2359CrossRefPubMed Cole BF, Baron JA, Sandler RS et al (2007) Folic acid for the prevention of colorectal adenomas-a randomized clinical trial. JAMA 297:2351–2359CrossRefPubMed
Zurück zum Zitat Cravo M, Fidalgo P, Pereira AD et al (1994) DNA methylation as an intermediate biomarker in colorectal cancer: modulation by folic acid supplementation. Eur J Cancer Prev 3:473–479CrossRefPubMed Cravo M, Fidalgo P, Pereira AD et al (1994) DNA methylation as an intermediate biomarker in colorectal cancer: modulation by folic acid supplementation. Eur J Cancer Prev 3:473–479CrossRefPubMed
Zurück zum Zitat Cravo ML, Pinto AG, Chaves P et al (1998a) Effect of folate supplementation on DNA methylation of rectal mucosa in patients with colonic adenomas: correlation with nutrient intake. Clin Nutr 17:45–49CrossRefPubMed Cravo ML, Pinto AG, Chaves P et al (1998a) Effect of folate supplementation on DNA methylation of rectal mucosa in patients with colonic adenomas: correlation with nutrient intake. Clin Nutr 17:45–49CrossRefPubMed
Zurück zum Zitat Cravo ML, Albuquerque CM, de Sousa S et al (1998b) Microsatellite instability in non-neoplastic mucosa of patients with ulcerative colitis: effect of folate supplementation. Am J Gastroenterol 93:2060–2064CrossRefPubMed Cravo ML, Albuquerque CM, de Sousa S et al (1998b) Microsatellite instability in non-neoplastic mucosa of patients with ulcerative colitis: effect of folate supplementation. Am J Gastroenterol 93:2060–2064CrossRefPubMed
Zurück zum Zitat Crott JW, Mashiyama ST, Ames BN, Fenech MF (2001a) Methylenetetrahydrofolate reductase C677T polymorphism does not alter folic acid deficiency-induced uracil incorporation into human lymphocyte DNA in vitro. Carcinogenesis 22:1019–1025CrossRefPubMed Crott JW, Mashiyama ST, Ames BN, Fenech MF (2001a) Methylenetetrahydrofolate reductase C677T polymorphism does not alter folic acid deficiency-induced uracil incorporation into human lymphocyte DNA in vitro. Carcinogenesis 22:1019–1025CrossRefPubMed
Zurück zum Zitat Crott JW, Mashiyama ST, Ames BN, Fenech M (2001b) The effect of folic acid deficiency and MTHFR C677T polymorphism on chromosome damage in human lymphocytes in vitro. Cancer Epidemiol Biomarker Prevent 10:1089–1096 Crott JW, Mashiyama ST, Ames BN, Fenech M (2001b) The effect of folic acid deficiency and MTHFR C677T polymorphism on chromosome damage in human lymphocytes in vitro. Cancer Epidemiol Biomarker Prevent 10:1089–1096
Zurück zum Zitat Crott JW, Liu ZH, Choi SW, Mason JB (2007) Folate depletion in human lymphocytes upregulates p53 expression despite marked induction of strand breaks in exons 5–8 of the gene. Mutat Res 626:171–179PubMed Crott JW, Liu ZH, Choi SW, Mason JB (2007) Folate depletion in human lymphocytes upregulates p53 expression despite marked induction of strand breaks in exons 5–8 of the gene. Mutat Res 626:171–179PubMed
Zurück zum Zitat De Boer J, Hoeijmakers JHJ (2000) Nucleotide excision repair and human syndromes. Carcinogenesis 21:453–460CrossRefPubMed De Boer J, Hoeijmakers JHJ (2000) Nucleotide excision repair and human syndromes. Carcinogenesis 21:453–460CrossRefPubMed
Zurück zum Zitat De Bont R, van Larebeke N (2004) Endogenous DNA damage in humans: a review of quantitative data. Mutagenesis 19:169–185CrossRefPubMed De Bont R, van Larebeke N (2004) Endogenous DNA damage in humans: a review of quantitative data. Mutagenesis 19:169–185CrossRefPubMed
Zurück zum Zitat DeVos L, Chanson A, Liu Z et al (2008) Associations between single nucleotide polymprphisms in folate uptake and metabolising genes with blood folate, homocysteine and DNA uracil concentrations. Am J Clin Nutr 88:1149–1158PubMed DeVos L, Chanson A, Liu Z et al (2008) Associations between single nucleotide polymprphisms in folate uptake and metabolising genes with blood folate, homocysteine and DNA uracil concentrations. Am J Clin Nutr 88:1149–1158PubMed
Zurück zum Zitat Doll R, Peto R (1981) The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. J Natl Cancer Inst 66:1191–11308PubMed Doll R, Peto R (1981) The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. J Natl Cancer Inst 66:1191–11308PubMed
Zurück zum Zitat Duthie SJ, McMillan P (1997) Uracil misincorporation in human DNA detected using single cell gel electrophoresis. Carcinogenesis 18:1709–1714CrossRefPubMed Duthie SJ, McMillan P (1997) Uracil misincorporation in human DNA detected using single cell gel electrophoresis. Carcinogenesis 18:1709–1714CrossRefPubMed
Zurück zum Zitat Duthie SJ, Hawdon A (1998) DNA stability (strand breakage, uracil misincorporation, and defective repair) is increased by folic acid depletion in human lymphocytes in vitro. FASEB J 12:1491–1497PubMed Duthie SJ, Hawdon A (1998) DNA stability (strand breakage, uracil misincorporation, and defective repair) is increased by folic acid depletion in human lymphocytes in vitro. FASEB J 12:1491–1497PubMed
Zurück zum Zitat Duthie SJ, Narayanan S, Blum S, Pirie L, Brand GM (2000a) Folate deficiency in vitro induces uracil misincorporation, DNA hypomethylation and inhibits DNA excision repair in immortalised normal human colon epithelial cells. Nutr Cancer 37:127–133CrossRef Duthie SJ, Narayanan S, Blum S, Pirie L, Brand GM (2000a) Folate deficiency in vitro induces uracil misincorporation, DNA hypomethylation and inhibits DNA excision repair in immortalised normal human colon epithelial cells. Nutr Cancer 37:127–133CrossRef
Zurück zum Zitat Duthie SJ, Grant G, Narayanan S (2000b) Increased uracil misincorporation in lymphocytes from folate-deficient rats. Brit J Cancer 83:1532–1537CrossRefPubMed Duthie SJ, Grant G, Narayanan S (2000b) Increased uracil misincorporation in lymphocytes from folate-deficient rats. Brit J Cancer 83:1532–1537CrossRefPubMed
Zurück zum Zitat Duthie SJ, Narayanan S, Brand GM, Grant G (2000c) DNA stability and genomic methylation status in colonocytes isolated from methyl-donor-deficient rats. Eur J Nutr 39:106–111CrossRefPubMed Duthie SJ, Narayanan S, Brand GM, Grant G (2000c) DNA stability and genomic methylation status in colonocytes isolated from methyl-donor-deficient rats. Eur J Nutr 39:106–111CrossRefPubMed
Zurück zum Zitat Duthie SJ, Mavrommatis Y, Rucklidge G et al (2008) The response of human colonocytes to folate deficiency in vitro: functional and proteomic analysis. J Proteome Res 7:3254–3266CrossRefPubMed Duthie SJ, Mavrommatis Y, Rucklidge G et al (2008) The response of human colonocytes to folate deficiency in vitro: functional and proteomic analysis. J Proteome Res 7:3254–3266CrossRefPubMed
Zurück zum Zitat Duthie SJ, Pirie LP, Grant G, Watson AJ, Margison GP (2010) Long term folate deficiency differentially alters hepatic and colon MGMT and OGG-1 DNA repair protein expression in rats but has no impact on genome-wide DNA methylation. Cancer Prev Res 3:92–100CrossRef Duthie SJ, Pirie LP, Grant G, Watson AJ, Margison GP (2010) Long term folate deficiency differentially alters hepatic and colon MGMT and OGG-1 DNA repair protein expression in rats but has no impact on genome-wide DNA methylation. Cancer Prev Res 3:92–100CrossRef
Zurück zum Zitat Ebbing M, Bleie O, Ueland PM et al (2008) Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary artery angiography: a randomised controlled trial. JAMA 300:795–804CrossRefPubMed Ebbing M, Bleie O, Ueland PM et al (2008) Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary artery angiography: a randomised controlled trial. JAMA 300:795–804CrossRefPubMed
Zurück zum Zitat Ebbing M, Bonaa KH, Nygard O et al (2009) Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA 302:2119–2126CrossRefPubMed Ebbing M, Bonaa KH, Nygard O et al (2009) Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA 302:2119–2126CrossRefPubMed
Zurück zum Zitat Fenech M, Aitken C, Rinaldi J (1998) Folate, vitamin B12, homocysteine status and DNA damage in young Australian adults. Carcinogenesis 19:1163–1171CrossRefPubMed Fenech M, Aitken C, Rinaldi J (1998) Folate, vitamin B12, homocysteine status and DNA damage in young Australian adults. Carcinogenesis 19:1163–1171CrossRefPubMed
Zurück zum Zitat Figueiredo JC, Grau MV, Wallace K et al (2009a) Globle DNA hypomethylation (LINE-1) in the normal colon and lifestyle characteristics and dietary and genetic factors. Cancer Epidemiol Biomark Prev 18:1041–1049CrossRef Figueiredo JC, Grau MV, Wallace K et al (2009a) Globle DNA hypomethylation (LINE-1) in the normal colon and lifestyle characteristics and dietary and genetic factors. Cancer Epidemiol Biomark Prev 18:1041–1049CrossRef
Zurück zum Zitat Figueiredo JC, Grau MV, Haile RW et al (2009b) Folic acid and risk of prostate cancer: results from a randomised clinical trial. J Natl Cancer Inst 101:432–435CrossRefPubMed Figueiredo JC, Grau MV, Haile RW et al (2009b) Folic acid and risk of prostate cancer: results from a randomised clinical trial. J Natl Cancer Inst 101:432–435CrossRefPubMed
Zurück zum Zitat Fortini P, Pascucci B, Parlanti E et al (2003) 8-oxoguanine DNA damage: at the crossroads of alternative repair pathways. Mutat Res 531:127–139PubMed Fortini P, Pascucci B, Parlanti E et al (2003) 8-oxoguanine DNA damage: at the crossroads of alternative repair pathways. Mutat Res 531:127–139PubMed
Zurück zum Zitat Friso S, Choi S-Y, Girelli D et al (2002) A common mutation in the 5, 10-methylenetetrahydrofolate reductase gene affects genomic DNA methylation status through an interaction with folate status. Proc Natl Acad Sci USA 99:5606–5611CrossRefPubMed Friso S, Choi S-Y, Girelli D et al (2002) A common mutation in the 5, 10-methylenetetrahydrofolate reductase gene affects genomic DNA methylation status through an interaction with folate status. Proc Natl Acad Sci USA 99:5606–5611CrossRefPubMed
Zurück zum Zitat Frosst P, Blom HJ, Milos R et al (1995) Candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10:111–113CrossRefPubMed Frosst P, Blom HJ, Milos R et al (1995) Candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10:111–113CrossRefPubMed
Zurück zum Zitat Giovannucci E (2002) Epidemiologic studies of folate and colorectal neoplasia: a review. J Nutr 132:2350S–2355SPubMed Giovannucci E (2002) Epidemiologic studies of folate and colorectal neoplasia: a review. J Nutr 132:2350S–2355SPubMed
Zurück zum Zitat Glynn SA, Albanes D (1994) Folate and cancer-a review of the literature. Nutr Cancer 22:101–119CrossRefPubMed Glynn SA, Albanes D (1994) Folate and cancer-a review of the literature. Nutr Cancer 22:101–119CrossRefPubMed
Zurück zum Zitat Hirsch S, Sanchez H, Alba C et al (2009) Colon cancer in Chile before and after the start of the flour fortification program with folic acid. Eur J Gastroenterol Hepatol 21:463–469CrossRef Hirsch S, Sanchez H, Alba C et al (2009) Colon cancer in Chile before and after the start of the flour fortification program with folic acid. Eur J Gastroenterol Hepatol 21:463–469CrossRef
Zurück zum Zitat Ingrosso D, Cimmino A, Perna AF, Masella L (2003) Folate treatment and unbalanced methylation and changes of allelic expression induced by hyperhomocysteinemia in patients with uremia. Blood 361:1693–1699 Ingrosso D, Cimmino A, Perna AF, Masella L (2003) Folate treatment and unbalanced methylation and changes of allelic expression induced by hyperhomocysteinemia in patients with uremia. Blood 361:1693–1699
Zurück zum Zitat Jacob RA, Gretz DM, Taylor PC et al (1998) Moderate folate depletion increases plasma homocysteine and decreases lymphocyte DNA methylation in postmenopausal women. J Nutr 128:1204–1212PubMed Jacob RA, Gretz DM, Taylor PC et al (1998) Moderate folate depletion increases plasma homocysteine and decreases lymphocyte DNA methylation in postmenopausal women. J Nutr 128:1204–1212PubMed
Zurück zum Zitat Jacques PF, Bostom AG, Williams RR et al (1996) Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation 93:7–9PubMed Jacques PF, Bostom AG, Williams RR et al (1996) Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation 93:7–9PubMed
Zurück zum Zitat James SJ, Yin L (1989) Diet-induced DNA damage and altered nucleotide metabolism in lymphocytes from methyl-donor-deficient rats. Carcinogenesis 10:1209–1214CrossRefPubMed James SJ, Yin L (1989) Diet-induced DNA damage and altered nucleotide metabolism in lymphocytes from methyl-donor-deficient rats. Carcinogenesis 10:1209–1214CrossRefPubMed
Zurück zum Zitat James SJ, Cross DR, Miller BJ (1992) Alterations in nucleotide pools in rats fed diets deficient in choline, methionine and/or folic acid. Carcinogenesis 13:2471–2474CrossRefPubMed James SJ, Cross DR, Miller BJ (1992) Alterations in nucleotide pools in rats fed diets deficient in choline, methionine and/or folic acid. Carcinogenesis 13:2471–2474CrossRefPubMed
Zurück zum Zitat James SJ, Pogribny IP, Pogribna M et al (2003) Mechanisms of DNA damage, DNA hypomethylation and tumour progression in the folate/methyl deficient rat model. J Nutr 133:3740S–3747SPubMed James SJ, Pogribny IP, Pogribna M et al (2003) Mechanisms of DNA damage, DNA hypomethylation and tumour progression in the folate/methyl deficient rat model. J Nutr 133:3740S–3747SPubMed
Zurück zum Zitat Kim YI (2007) Folate and colorectal cancer: an evidence-based critical review. Mol Nutr Food Res 51:267–292CrossRefPubMed Kim YI (2007) Folate and colorectal cancer: an evidence-based critical review. Mol Nutr Food Res 51:267–292CrossRefPubMed
Zurück zum Zitat Kim YI, Salomon RN, Graeme-Cook F, Choi SW (1996a) Dietary folate protects against the development of macroscopic colonic neoplasia in a dose-dependent manner in rats. Gut 39:732–740CrossRefPubMed Kim YI, Salomon RN, Graeme-Cook F, Choi SW (1996a) Dietary folate protects against the development of macroscopic colonic neoplasia in a dose-dependent manner in rats. Gut 39:732–740CrossRefPubMed
Zurück zum Zitat Kim Y-I, Pogribny IP, Salomon RN et al (1996b) Exon-specific DNA hypomethylation of the p53 gene of rat colon induced by dimethylhydrazine: modulation by dietary folate. Am J Clin Pathol 149:1129–1137 Kim Y-I, Pogribny IP, Salomon RN et al (1996b) Exon-specific DNA hypomethylation of the p53 gene of rat colon induced by dimethylhydrazine: modulation by dietary folate. Am J Clin Pathol 149:1129–1137
Zurück zum Zitat Kim Y-I, Shirwadkar S, Choi S-W et al (2000) Effects of dietary folate on DNA strand breaks within mutation-prone exons of the p53 gene in rat colon. Gastroenterol 119:151–161CrossRef Kim Y-I, Shirwadkar S, Choi S-W et al (2000) Effects of dietary folate on DNA strand breaks within mutation-prone exons of the p53 gene in rat colon. Gastroenterol 119:151–161CrossRef
Zurück zum Zitat Kono S, Chen K (2005) Genetic polymorphisms of methylenetetrahydrofolate reductase and colorectal cancer and adenoma. Cancer Sci 96:535–542CrossRefPubMed Kono S, Chen K (2005) Genetic polymorphisms of methylenetetrahydrofolate reductase and colorectal cancer and adenoma. Cancer Sci 96:535–542CrossRefPubMed
Zurück zum Zitat Krugman II, Kumaravel TS, Lohani A et al (2002) Folic acid deficiency and homocysteine impair DNA repair in hippocampal neurons and sensitise them to amyloid toxicity in experimental models of Alzheimer’s disease. J Neurosci 22:1752–1762 Krugman II, Kumaravel TS, Lohani A et al (2002) Folic acid deficiency and homocysteine impair DNA repair in hippocampal neurons and sensitise them to amyloid toxicity in experimental models of Alzheimer’s disease. J Neurosci 22:1752–1762
Zurück zum Zitat Ma J, Stampfer MJ, Giovannucci E et al (1997) Methylenetetrahydrofolate reductase polymorphism: dietary interactions and risk of colorectal cancer. Cancer Res 57:1098–1102PubMed Ma J, Stampfer MJ, Giovannucci E et al (1997) Methylenetetrahydrofolate reductase polymorphism: dietary interactions and risk of colorectal cancer. Cancer Res 57:1098–1102PubMed
Zurück zum Zitat Mason JB, Dickstein A, Jacques PF et al (2007) A temporal association between folic acid fortification and an increase in colorectal cancer rates may be illuminating important biological principles: a hypothesis. Cancer Epidemiol Biomark Prev 16:1325–1329CrossRef Mason JB, Dickstein A, Jacques PF et al (2007) A temporal association between folic acid fortification and an increase in colorectal cancer rates may be illuminating important biological principles: a hypothesis. Cancer Epidemiol Biomark Prev 16:1325–1329CrossRef
Zurück zum Zitat Melnyk S, Pogribny M, Miller BJ et al (1999) Uracil misincorporation, DNA strand breaks and gene amplification are associated with tumorigenic cell transformation in folate deficient/repleted Chinese hamster ovary cells. Cancer Letts 146:35–44CrossRef Melnyk S, Pogribny M, Miller BJ et al (1999) Uracil misincorporation, DNA strand breaks and gene amplification are associated with tumorigenic cell transformation in folate deficient/repleted Chinese hamster ovary cells. Cancer Letts 146:35–44CrossRef
Zurück zum Zitat Narayanan S, McConnell J, Little J et al (2004) Methylenetetrahydrofolate reductase gene: association with folate metabolism and DNA stability (strand breaks, misincorporated uracil and DNA methylation status). Cancer Epidemiol Biomark Prev 13:1–8 Narayanan S, McConnell J, Little J et al (2004) Methylenetetrahydrofolate reductase gene: association with folate metabolism and DNA stability (strand breaks, misincorporated uracil and DNA methylation status). Cancer Epidemiol Biomark Prev 13:1–8
Zurück zum Zitat Paz MF, Avila S, Fraga MF et al (2002) Germ-line variants in methyl-group metabolism genes and susceptibility to DNA methylation in normal tissues and human primary tumours. Cancer Res 62:4519–4524PubMed Paz MF, Avila S, Fraga MF et al (2002) Germ-line variants in methyl-group metabolism genes and susceptibility to DNA methylation in normal tissues and human primary tumours. Cancer Res 62:4519–4524PubMed
Zurück zum Zitat Pogribny IP, Muskheloshvili L, Miller BJ, James SJ (1997) Presence and consequence of uracil in preneoplastic DNA from folate/methyl-deficient rats. Carcinogenesis 18:2071–2076CrossRefPubMed Pogribny IP, Muskheloshvili L, Miller BJ, James SJ (1997) Presence and consequence of uracil in preneoplastic DNA from folate/methyl-deficient rats. Carcinogenesis 18:2071–2076CrossRefPubMed
Zurück zum Zitat Pogribny IP, James SJ, Jernigan S, Pogribna M (2004) Genomic hypomethylation is specific for preneoplastic liver in folate/methyl deficient rats and does not occur in non-target tissues. Mutat Res 548:53–59PubMed Pogribny IP, James SJ, Jernigan S, Pogribna M (2004) Genomic hypomethylation is specific for preneoplastic liver in folate/methyl deficient rats and does not occur in non-target tissues. Mutat Res 548:53–59PubMed
Zurück zum Zitat Povey AC, Lees NP, Harrison KL, Hall CN, Margison GP (2002) Altered O-6-alkylguanine DNA alkyltransferase (MGMT) activity in normal colorectal tissue and adenomas is associated with K-ras GC-AT gene mutations. Proc Am Assoc Cancer Res 5049:1020 Povey AC, Lees NP, Harrison KL, Hall CN, Margison GP (2002) Altered O-6-alkylguanine DNA alkyltransferase (MGMT) activity in normal colorectal tissue and adenomas is associated with K-ras GC-AT gene mutations. Proc Am Assoc Cancer Res 5049:1020
Zurück zum Zitat Pufulete M, Al-Ghnaniem R, Khushal A et al (2005) Effect of folic acid supplementation on genomic DNA methylation in patients with colorectal adenoma. Gut 54:648–653CrossRefPubMed Pufulete M, Al-Ghnaniem R, Khushal A et al (2005) Effect of folic acid supplementation on genomic DNA methylation in patients with colorectal adenoma. Gut 54:648–653CrossRefPubMed
Zurück zum Zitat Quinlivan EP, Davis SR, Shelnutt KP et al (2005) Methylenetetrahydrofolate reductase 677C-T polymorphism anf folate status affect one-carbon incorporation into human DNA deoxynucleosides. J Nutr 135:389–396PubMed Quinlivan EP, Davis SR, Shelnutt KP et al (2005) Methylenetetrahydrofolate reductase 677C-T polymorphism anf folate status affect one-carbon incorporation into human DNA deoxynucleosides. J Nutr 135:389–396PubMed
Zurück zum Zitat Rampersaud GC, Kauwell GPA, Cerda HAD, JJ BLB (2000) Genomic DNA methylation decreases in response to moderate folate depletion in elderly women. Am J Clin Nutr 72:998–1003PubMed Rampersaud GC, Kauwell GPA, Cerda HAD, JJ BLB (2000) Genomic DNA methylation decreases in response to moderate folate depletion in elderly women. Am J Clin Nutr 72:998–1003PubMed
Zurück zum Zitat Reidy JA (1988) Role of deoxyuridine incorporation and DNA repair in the expression of human chromosomal fragile sites. Mutat Res 211:215–220 Reidy JA (1988) Role of deoxyuridine incorporation and DNA repair in the expression of human chromosomal fragile sites. Mutat Res 211:215–220
Zurück zum Zitat Sanjoaquin MA, Allen N, Couto E, Roddam AW, Key TJ (2005) Folate intake and colorectal cancer risk: a meta-analytical approach. Int J Cancer 113:825–828CrossRefPubMed Sanjoaquin MA, Allen N, Couto E, Roddam AW, Key TJ (2005) Folate intake and colorectal cancer risk: a meta-analytical approach. Int J Cancer 113:825–828CrossRefPubMed
Zurück zum Zitat Schernhammer ES, Giovannucci E, Kawasaki T et al (2009) Dietary folate, alcohol and B vitamins in relation to LINE-1 hypomethylation in colon cancer. Gut (e-pub ahead of print) Schernhammer ES, Giovannucci E, Kawasaki T et al (2009) Dietary folate, alcohol and B vitamins in relation to LINE-1 hypomethylation in colon cancer. Gut (e-pub ahead of print)
Zurück zum Zitat Sharp L, Little J (2004) Polymorphisms in genes involved in folate metabolism and colorectal neoplasia: a HuGE review. Am J Epidemiol 159:423–443CrossRefPubMed Sharp L, Little J (2004) Polymorphisms in genes involved in folate metabolism and colorectal neoplasia: a HuGE review. Am J Epidemiol 159:423–443CrossRefPubMed
Zurück zum Zitat Sohn Y-J, Stempack JM, Reid S et al (2003) The effect of dietary folate on genomic and p53-specific DNA methylation in rat colon. Carcinogenesis 24:81–90CrossRefPubMed Sohn Y-J, Stempack JM, Reid S et al (2003) The effect of dietary folate on genomic and p53-specific DNA methylation in rat colon. Carcinogenesis 24:81–90CrossRefPubMed
Zurück zum Zitat Sohn KJ, Jang H, Campan M et al (2009) The methylenetetrahydrofolate reductase C677T mutation induces cell-specific changes in genomic DNA methylation and uracil misincorporation: a possible molecular basis for the site-specific cancer modification. Int J Cancer 124:1999–2005CrossRefPubMed Sohn KJ, Jang H, Campan M et al (2009) The methylenetetrahydrofolate reductase C677T mutation induces cell-specific changes in genomic DNA methylation and uracil misincorporation: a possible molecular basis for the site-specific cancer modification. Int J Cancer 124:1999–2005CrossRefPubMed
Zurück zum Zitat Song J, Medline A, Mason JB, Gallinger S, Kim Y-I (2000a) Effects of dietary folate on intestinal tumorigenesis in the ApcMin Msh mouse. Cancer Res 60:3191–3199PubMed Song J, Medline A, Mason JB, Gallinger S, Kim Y-I (2000a) Effects of dietary folate on intestinal tumorigenesis in the ApcMin Msh mouse. Cancer Res 60:3191–3199PubMed
Zurück zum Zitat Song J, Sohn K-J, Medline A, Ash C, Gallinger S, Kim Y-I (2000b) Chemopreventive effects of dietary folate on intestinal polyps in Apc+/-Msh-/-mice. Cancer Res 6:3191–3199 Song J, Sohn K-J, Medline A, Ash C, Gallinger S, Kim Y-I (2000b) Chemopreventive effects of dietary folate on intestinal polyps in Apc+/-Msh-/-mice. Cancer Res 6:3191–3199
Zurück zum Zitat Stempak JM, Sohn K-Y, Chiang E-P, Shane B, Kim Y-I (2005) Cell and stage of transformation-specific effects of folate deficiency on methionine cycle intermediates and DNA methylation in an in vitro model. Carcinogenesis 26:981–990CrossRefPubMed Stempak JM, Sohn K-Y, Chiang E-P, Shane B, Kim Y-I (2005) Cell and stage of transformation-specific effects of folate deficiency on methionine cycle intermediates and DNA methylation in an in vitro model. Carcinogenesis 26:981–990CrossRefPubMed
Zurück zum Zitat Stern LL, Mason JB, Selhub J, Choi SW (2000) Genomic DNA hypomethylation, a characteristic of most cancers, is present in peripheral leukocytes of individuals who are homozygous for the C677T polymorphism in the methylenetetrahydrofolate reductase gene. Cancer Epidemiol Biomark Prev 9:849–853 Stern LL, Mason JB, Selhub J, Choi SW (2000) Genomic DNA hypomethylation, a characteristic of most cancers, is present in peripheral leukocytes of individuals who are homozygous for the C677T polymorphism in the methylenetetrahydrofolate reductase gene. Cancer Epidemiol Biomark Prev 9:849–853
Zurück zum Zitat Stolzenberg-Solomon RZ, Chang SC, Leitzmann MF et al (2006) Folate intake, alcohol use and postmenopausal breast cancer risk in the Prostate Lung Colorectal and Ovarian Cancer Screening Trial. Am J Clin Nutr 83:895–904PubMed Stolzenberg-Solomon RZ, Chang SC, Leitzmann MF et al (2006) Folate intake, alcohol use and postmenopausal breast cancer risk in the Prostate Lung Colorectal and Ovarian Cancer Screening Trial. Am J Clin Nutr 83:895–904PubMed
Zurück zum Zitat van den Donk M, Pellis L, Crott JW et al (2007) Folic acid and vitamin B12 supplementation does not favorably influence uracil misincorporation and promoter methylation in rectal mucosa DNA of subjects with previous colorectal adenomas. J Nutr 137:2114–2120PubMed van den Donk M, Pellis L, Crott JW et al (2007) Folic acid and vitamin B12 supplementation does not favorably influence uracil misincorporation and promoter methylation in rectal mucosa DNA of subjects with previous colorectal adenomas. J Nutr 137:2114–2120PubMed
Zurück zum Zitat Wainfan E, Poirier LA (1992) Methyl groups in carcinogenesis: effects on DNA methylation and gene expression. Cancer Res 52:2071s–2077sPubMed Wainfan E, Poirier LA (1992) Methyl groups in carcinogenesis: effects on DNA methylation and gene expression. Cancer Res 52:2071s–2077sPubMed
Zurück zum Zitat Wasson GR, McGlynn AP, McNulty H et al (2006) Global DNA and p53 region-specific hypomethylation in human colonic cells is induced by folate depletion and reversed by folate supplementation. J Nutr 136:2748–2753PubMed Wasson GR, McGlynn AP, McNulty H et al (2006) Global DNA and p53 region-specific hypomethylation in human colonic cells is induced by folate depletion and reversed by folate supplementation. J Nutr 136:2748–2753PubMed
Zurück zum Zitat Wei Q, Shen H, Wang LE et al (2003) Association between low dietary folate intake and suboptimal cellular DNA repair capacity. Cancer Epidemiol Biomark Prev 12:963–969 Wei Q, Shen H, Wang LE et al (2003) Association between low dietary folate intake and suboptimal cellular DNA repair capacity. Cancer Epidemiol Biomark Prev 12:963–969
Zurück zum Zitat Whitehouse A, Meredith DM, Markham AF (1998) DNA mismatch repair genes and their association with colorectal cancer. Int J Mol Med 1:469–474PubMed Whitehouse A, Meredith DM, Markham AF (1998) DNA mismatch repair genes and their association with colorectal cancer. Int J Mol Med 1:469–474PubMed
Zurück zum Zitat Wickramasinghe SN, Fida S (1994) Bone marrow cells from vitamin B12-and folate-deficient patients misincorporate uracil into DNA. Blood 83:1656–1661PubMed Wickramasinghe SN, Fida S (1994) Bone marrow cells from vitamin B12-and folate-deficient patients misincorporate uracil into DNA. Blood 83:1656–1661PubMed
Zurück zum Zitat World Cancer Research Fund (2007) Food, nutrition, physical activity and the prevention of cancer: a global perspective. American Institute of Cancer Research, Washington World Cancer Research Fund (2007) Food, nutrition, physical activity and the prevention of cancer: a global perspective. American Institute of Cancer Research, Washington
Zurück zum Zitat Yang Q, Bostick RM, Friedman JM, Flanders WD (2009) Serum folate and cancer mortality among US adults: findings from the third national health and nutritional examination survey linked mortality file. Cancer Epidemiol Biomark Prev 18:1439–1447CrossRef Yang Q, Bostick RM, Friedman JM, Flanders WD (2009) Serum folate and cancer mortality among US adults: findings from the third national health and nutritional examination survey linked mortality file. Cancer Epidemiol Biomark Prev 18:1439–1447CrossRef
Zurück zum Zitat Zijno A, Andreoli C, Leopardi P et al (2003) Folate status, metabolic genotype and biomarkers of genotoxicity in healthy subjects. Carcinogenesis 24:1097–1103CrossRefPubMed Zijno A, Andreoli C, Leopardi P et al (2003) Folate status, metabolic genotype and biomarkers of genotoxicity in healthy subjects. Carcinogenesis 24:1097–1103CrossRefPubMed
Metadaten
Titel
Folate and cancer: how DNA damage, repair and methylation impact on colon carcinogenesis
verfasst von
Susan J. Duthie
Publikationsdatum
01.02.2011
Verlag
Springer Netherlands
Erschienen in
Journal of Inherited Metabolic Disease / Ausgabe 1/2011
Print ISSN: 0141-8955
Elektronische ISSN: 1573-2665
DOI
https://doi.org/10.1007/s10545-010-9128-0

Weitere Artikel der Ausgabe 1/2011

Journal of Inherited Metabolic Disease 1/2011 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.