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

Arasaradam RP, Commane DM, Bradburn D et al (2008) A review of dietary factors and its influence on DNA methylation in colorectal carcinogenesis. Epigenetics 3:193–198 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 95:13217–13220 Balaghi M, Wagner C (1993) DNA methylation in folate deficiency: use of CpG methylase. Biochem Biophys Res Commun 193:1184–1190 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 94:1942–1947 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 578:317–326 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 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 30:615–620 Blount BC, Ames BN (1994) Analysis of uracil in DNA by gas chromatography-mass spectometry. Anal Biochem 219:195–200 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 94:3290–3295 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 354:1578–1588 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 57:2586–2588 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 615:12–17 Chen J, Giovannucci E, Kelsey K et al (1996) A methylenetetrahydrofolate reductase polymorphism and the risk of colorectal cancer. Cancer Res 56:4862–4864 Choi S-W, Kim Y-I, Weitzel JN, Mason JB (1998) Folate depletion impairs DNA excision repair in the colon of the rat. Gut 43:93–99 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 Christmann M, Tomicic MT, Rood WP, Kaina B (2003) Mechanisms of human DNA repair: an update. Toxicology 193:3–34 Cole BF, Baron JA, Sandler RS et al (2007) Folic acid for the prevention of colorectal adenomas-a randomized clinical trial. JAMA 297:2351–2359 Costello JF, Plass C (2001) Methylation matters. J Med Genet 38:285–303 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 3:473–479 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 17:45–49 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 93:2060–2064 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 22:1019–1025 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, 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 626:171–179 De Boer J, Hoeijmakers JHJ (2000) Nucleotide excision repair and human syndromes. Carcinogenesis 21:453–460 De Bont R, van Larebeke N (2004) Endogenous DNA damage in humans: a review of quantitative data. Mutagenesis 19:169–185 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 88:1149–1158 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 66:1191–11308 Duthie SJ, McMillan P (1997) Uracil misincorporation in human DNA detected using single cell gel electrophoresis. Carcinogenesis 18:1709–1714 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 12:1491–1497 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 37:127–133 Duthie SJ, Grant G, Narayanan S (2000b) Increased uracil misincorporation in lymphocytes from folate-deficient rats. Brit J Cancer 83:1532–1537 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 39:106–111 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 7:3254–3266 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 3:92–100 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 300:795–804 Ebbing M, Bonaa KH, Nygard O et al (2009) Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA 302:2119–2126 Fenech M, Aitken C, Rinaldi J (1998) Folate, vitamin B12, homocysteine status and DNA damage in young Australian adults. Carcinogenesis 19:1163–1171 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 18:1041–1049 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 101:432–435 Fortini P, Pascucci B, Parlanti E et al (2003) 8-oxoguanine DNA damage: at the crossroads of alternative repair pathways. Mutat Res 531:127–139 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 99:5606–5611 Frosst P, Blom HJ, Milos R et al (1995) Candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10:111–113 Giovannucci E (2002) Epidemiologic studies of folate and colorectal neoplasia: a review. J Nutr 132:2350S–2355S Glynn SA, Albanes D (1994) Folate and cancer-a review of the literature. Nutr Cancer 22:101–119 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 21:463–469 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 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 128:1204–1212 Jacques PF, Bostom AG, Williams RR et al (1996) Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation 93:7–9 James SJ, Yin L (1989) Diet-induced DNA damage and altered nucleotide metabolism in lymphocytes from methyl-donor-deficient rats. Carcinogenesis 10:1209–1214 James SJ, Cross DR, Miller BJ (1992) Alterations in nucleotide pools in rats fed diets deficient in choline, methionine and/or folic acid. Carcinogenesis 13:2471–2474 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–3747S Kim YI (2007) Folate and colorectal cancer: an evidence-based critical review. Mol Nutr Food Res 51:267–292 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 39:732–740 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, 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 119:151–161 Kono S, Chen K (2005) Genetic polymorphisms of methylenetetrahydrofolate reductase and colorectal cancer and adenoma. Cancer Sci 96:535–542 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 Ma J, Stampfer MJ, Giovannucci E et al (1997) Methylenetetrahydrofolate reductase polymorphism: dietary interactions and risk of colorectal cancer. Cancer Res 57:1098–1102 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 16:1325–1329 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 146:35–44 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 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 62:4519–4524 Pogribny IP, Muskheloshvili L, Miller BJ, James SJ (1997) Presence and consequence of uracil in preneoplastic DNA from folate/methyl-deficient rats. Carcinogenesis 18:2071–2076 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 548:53–59 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 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 54:648–653 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 135:389–396 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 72:998–1003 Reidy JA (1988) Role of deoxyuridine incorporation and DNA repair in the expression of human chromosomal fragile sites. Mutat Res 211:215–220 Sanjoaquin MA, Allen N, Couto E, Roddam AW, Key TJ (2005) Folate intake and colorectal cancer risk: a meta-analytical approach. Int J Cancer 113:825–828 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) Sharp L, Little J (2004) Polymorphisms in genes involved in folate metabolism and colorectal neoplasia: a HuGE review. Am J Epidemiol 159:423–443 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 24:81–90 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 124:1999–2005 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 60:3191–3199 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 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 26:981–990 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 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 83:895–904 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 137:2114–2120 Wainfan E, Poirier LA (1992) Methyl groups in carcinogenesis: effects on DNA methylation and gene expression. Cancer Res 52:2071s–2077s 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 136:2748–2753 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 Whitehouse A, Meredith DM, Markham AF (1998) DNA mismatch repair genes and their association with colorectal cancer. Int J Mol Med 1:469–474 Wickramasinghe SN, Fida S (1994) Bone marrow cells from vitamin B12-and folate-deficient patients misincorporate uracil into DNA. Blood 83:1656–1661 World Cancer Research Fund (2007) Food, nutrition, physical activity and the prevention of cancer: a global perspective. American Institute of Cancer Research, Washington 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 18:1439–1447 Zijno A, Andreoli C, Leopardi P et al (2003) Folate status, metabolic genotype and biomarkers of genotoxicity in healthy subjects. Carcinogenesis 24:1097–1103