Abstract
In relation to the genome, investigation of the epigenome is emerging as an equal, if not more influential factor in modulating human health and disease. Since epigenetic modifications are gradual in onset and potentially reversible, determining factors that modulate the epigenome is critical for possible preventive and therapeutic interventions. The development and progression of cancer is mechanistically linked to a number of epigenetic changes, including global DNA hypomethylation and gene-specific CpG promoter DNA hypermethylation. Environmental factors, including diet, have been shown to affect cancer risk, via epigenetic and non-epigenetic mechanisms. In this regard, one-carbon nutrients are prototypic dietary factors that may modulate cancer risk via epigenetic mechanisms. This chapter will discuss the role of nutrients involved in one-carbon metabolism and their effect on cancer risk via epigenetic modifications with a particular focus on DNA methylation.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
(1998) Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. The National Academies Press, Washington, DC
Abbadi RA-G, Emery P, Pufulete M (2012) Short-term folate supplementation in physiological doses has no effect on ESR1 and MLH1 methylation in colonic mucosa of individuals with adenoma. J Nutrigenet Nutrigenomics 5:327–338
Abratte CM, Wang W, Li R, Axume J, Moriarty DJ, Caudill MA (2009) Choline status is not a reliable indicator of moderate changes in dietary choline consumption in premenopausal women. J Nutr Biochem 20:62–69
Ackerstaff E, Pflug BR, Nelson JB, Bhujwalla ZM (2001) Detection of increased choline compounds with proton nuclear magnetic resonance spectroscopy subsequent to malignant transformation of human prostatic epithelial cells. Cancer Res 61:3599–3603
Alberg AJ, Selhub J, Shah KV, Viscidi RP, Comstock GW, Helzlsouer KJ (2000) The risk of cervical cancer in relation to serum concentrations of folate, vitamin B-12, and homocysteine. Cancer Epidemiol Biomarkers Prev 9:761–764
Albert CM, Cook NR, Gaziano JM, Zaharris E, Macfadyen J, Danielson E, Buring JE, Manson JE (2008) Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: a randomized trial. JAMA 299:2027–2036
Al-Ghnaniem R, Peters J, Foresti R, Heaton N, Pufulete M (2007) Methylation of estrogen receptor alpha and mutL homolog 1 in normal colonic mucosa: association with folate and vitamin B-12 status in subjects with and without colorectal neoplasia. Am J Clin Nutr 86:1064–1072
Alonso-Aperte E, Gonzalez MP, Poo-Prieto R, Varela-Moreiras G (2008) Folate status and S-adenosylmethionine/S-adenosylhomocysteine ratio in colorectal adenocarcinoma in humans. Eur J Clin Nutr 62:295–298
Alvarez H, Opalinska J, Zhou L, Sohal D, Fazzari MJ, Yu YT, Montagna C, Montgomery EA, Canto M, Dunbar KB, Wang J, Roa JC, Mo YK, Bhagat T, Ramesh KH, Cannizzaro L, Mollenhauer J, Thompson RF, Suzuki M, Meltzer SJ, Melnick A, Greally JM, Maitra A, Verma A (2011) Widespread hypomethylation occurs early and synergizes with gene amplification during esophageal carcinogenesis. PLoS Genet 7
Asada K, Kotake Y, Asada R, Saunders D, Broyles RH, Towner RA, Fukui H, Floyd RA (2006) LINE-1 hypomethylation in a choline-deficiency-induced liver cancer in rats: dependence on feeding period. J Biomed Biotechnol 2006:17142
Aufreiter S, Gregory JF, Pfeiffer CM, Fazili Z, Kim YI, Marcon N, Kamalaporn P, Pencharz PB, O’Connor DL (2009) Folate is absorbed across the colon of adults: evidence from cecal infusion of C-13-labeled 6S–5-formyltetrahydrofolic acid. Am J Clin Nutr 90:116–123
Ba Y, Yu H, Liu F, Geng X, Zhu C, Zhu Q, Zheng T, Ma S, Wang G, Li Z, Zhang Y (2011) Relationship of folate, vitamin B12 and methylation of insulin-like growth factor-II in maternal and cord blood. Eur J Clin Nutr 65:480–485
Baggott JE, Vaughn WH, Juliana MM, Eto I, Krumdieck CL, Grubbs CJ (1992) Effects of folate-deficiency and supplementation on methylnitrosourea-induced RAT mammary-tumors. J Natl Cancer Inst 84:1740–1744
Baghurst PA, McMichael AJ, Slavotinek AH, Baghurst KI, Boyle P, Walker AM (1991) A case-control study of diet and cancer of the pancreas. Am J Epidemiol 134:167–179
Bailey LB (2003) Folate, methyl-related nutrients, alcohol, and the MTHFR 677C → T polymorphism affect cancer risk: intake recommendations. J Nutr 133:3748S–3753S
Bailey SW, Ayling JE (2009) The extremely slow and variable activity of dihydrofolate reductase in human liver and its implications for high folic acid intake. Proc Natl Acad Sci U S A 106:15424–15429
Bailey HD, Miller M, Langridge A, De Klerk NH, Van Bockxmeer FM, Attia J, Scott RJ, Armstrong BK, Milne E (2012) Maternal dietary intake of folate and vitamins B6 and B12 during pregnancy and the risk of childhood acute lymphoblastic leukemia. Nutr Cancer 64:1122–1130
Balch C, Matei DE, Huang TH, Nephew KP (2010) Role of epigenomics in ovarian and endometrial cancers. Epigenomics 2:419–447
Balk EM, Raman G, Tatsioni A, Chung M, Lau J, Rosenberg IH (2007) Vitamin B6, B12, and folic acid supplementation and cognitive function: a systematic review of randomized trials. Arch Intern Med 167:21–30
Ballestar E, Esteller M (2002) The impact of chromatin in human cancer: linking DNA methylation to gene silencing. Carcinogenesis 23:1103–1109
Banno K, Kisu I, Yanokura M, Masuda K, Kobayashi Y, Ueki A, Tsuji K, Yamagami W, Nomura H, Susumu N, Aoki D (2012) Endometrial cancer and hypermethylation: regulation of DNA and MicroRNA by epigenetics. Biochem Res Int 2012:738274
Bassett JK, Severi G, Hodge AM, Baglietto L, Hopper JL, English DR, Giles GG (2012) Dietary intake of B vitamins and methionine and prostate cancer incidence and mortality. Cancer Causes Control 23:855–863
Basten GP, Duthie SJ, Pirie L, Vaughan N, Hill MH, Powers HJ (2006) Sensitivity of markers of DNA stability and DNA repair activity to folate supplementation in healthy volunteers. Br J Cancer 94:1942–1947
Beilby J, Ambrosini GL, Rossi E, De Klerk NH, Musk AW (2010) Serum levels of folate, lycopene, beta-carotene, retinol and vitamin E and prostate cancer risk. Eur J Clin Nutr 64:1235–1238
Berner C, Aumuller E, Gnauck A, Nestelberger M, Just A, Haslberger AG (2010) Epigenetic control of estrogen receptor expression and tumor suppressor genes is modulated by bioactive food compounds. Ann Nutr Metab 57:183–189
Biasco G, Zannoni U, Paganelli GM, Santucci R, Gionchetti P, Rivolta G, Miniero R, Pironi L, Calabrese C, Di Febo G, Miglioli M (1997) Folic acid supplementation and cell kinetics of rectal mucosa in patients with ulcerative colitis. Cancer Epidemiol Biomarkers Prev 6:469–471
Biel RK, Csizmadi I, Cook LS, Courneya KS, Magliocco AM, Friedenreich CM (2011) Risk of endometrial cancer in relation to individual nutrients from diet and supplements. Public Health Nutr 14:1948–1960
Bird AP, Wolffe AP (1999) Methylation-induced repression–belts, braces, and chromatin. Cell 99:451–454
Bistulfi G, Foster BA, Karasik E, Gillard B, Miecznikowski J, Dhiman VK, Smiraglia DJ (2011) Dietary folate deficiency blocks prostate cancer progression in the TRAMP model. Cancer Prev Res 4:1825–1834
Boeke CE, Baccarelli A, Kleinman KP, Burris HH, Litonjua AA, Rifas-Shiman SL, Tarantini L, Gillman MW (2012) Gestational intake of methyl donors and global LINE-1 DNA methylation in maternal and cord blood Prospective results from a folate-replete population. Epigenetics 7:253–260
Bravi F, Edefonti V, Randi G, Garavello W, La Vecchia C, Ferraroni M, Talamini R, Franceschi S, Decarli A (2012) Dietary patterns and the risk of esophageal cancer. Ann Oncol 23:765–770
Bunin GR, Meadows AT, Emanuel BS, Buckley JD, Woods WG, Hammond GD (1989) Pre- and postconception factors associated with sporadic heritable and nonheritable retinoblastoma. Cancer Res 49:5730–5735
Bunin GR, Kuijten RR, Buckley JD, Rorke LB, Meadows AT (1993) Relation between maternal diet and subsequent primitive neuroectodermal brain tumors in young children. N Engl J Med 329:536–541
Bunin GR, Gallagher PR, Rorke-Adams LB, Robison LL, Cnaan A (2006) Maternal supplement, micronutrient, and cured meat intake during pregnancy and risk of medulloblastoma during childhood: a children’s oncology group study. Cancer Epidemiol Biomarkers Prev 15:1660–1667
Calcagno DQ, Leal MF, Assumpcao PP, Smith MA, Burbano RR (2008) MYC and gastric adenocarcinoma carcinogenesis. World J Gastroenterol 14:5962–5968
Calcagno DQ, Gigek CO, Chen ES, Burbano RR, Smith MA (2013) DNA and histone methylation in gastric carcinogenesis. World J Gastroenterol 19:1182–1192
Canman CE, Lim DS, Cimprich KA, Taya Y, Tamai K, Sakaguchi K, Appella E, Kastan MB, Siliciano JD (1998) Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. Science 281:1677–1679
Carroll C, Cooper K, Papaioannou D, Hind D, Tappenden P, Pilgrim H, Booth A (2010) Meta-analysis: folic acid in the chemoprevention of colorectal adenomas and colorectal cancer. Aliment Pharmacol Ther 31:708–718
Castro R, Rivera I, Ravasco P, Camilo ME, Jakobs C, Blom HJ, De Almeida IT (2004) 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C → T and 1298A → C mutations are associated with DNA hypomethylation. J Med Genet 41:454–458
Chagas CE, Bassoli BK, De Souza CA, Deminice R, Jordao Junior AA, Paiva SA, Dagli ML, Ong TP, Moreno FS (2011) Folic acid supplementation during early hepatocarcinogenesis: cellular and molecular effects. Int J Cancer 129:2073–2082
Charles MA, Johnson IT, Belshaw NJ (2012) Supra-physiological folic acid concentrations induce aberrant DNA methylation in normal human cells in vitro. Epigenetics 7:689–694
Chen J, Gammon MD, Chan W, Palomeque C, Wetmur JG, Kabat GC, Teitelbaum SL, Britton JA, Terry MB, Neugut AI, Santella RM (2005) One-carbon metabolism, MTHFR polymorphisms, and risk of breast cancer. Cancer Res 65:1606–1614
Chen J, Huang Z-J, Duan Y-Q, Xiao X-R, Jiang J-Q, Zhang R (2012) Aberrant DNA methylation of P16, MGMT, and hMLH1 genes in combination with MTHFR C677T genetic polymorphism and folate intake in esophageal squamous cell carcinoma. Asian Pac J Cancer Prev 13:5303–5306
Chen F-P, Lin C-C, Chen T-H, Tsai M-C, Huang Y-C (2013) Higher plasma homocysteine is associated with increased risk of developing colorectal polyps. Nutr Cancer 65:195–201
Cheng YW, Idrees K, Shattock R, Khan SA, Zeng Z, Brennan CW, Paty P, Barany F (2010) Loss of imprinting and marked gene elevation are 2 forms of aberrant IGF2 expression in colorectal cancer. Int J Cancer 127:568–577
Cho E, Willett WC, Colditz GA, Fuchs CS, Wu K, Chan AT, Zeisel SH, Giovannucci EL (2007a) Dietary choline and betaine and the risk of distal colorectal adenoma in women. J Natl Cancer Inst 99:1224–1231
Cho EY, Holmes M, Hankinson SE, Willett WC (2007b) Nutrients involved in one-carbon metabolism and risk of breast cancer among premenopausal women. Cancer Epidemiol Biomarkers Prev 16:2787–2790
Choi SW, Kim YI, Weitzel JN, Mason JB (1998) Folate depletion impairs DNA excision repair in the colon of the rat. Gut 43:93–99
Choi SW, Friso S, Dolnikowski GG, Bagley PJ, Edmondson AN, Smith DE, Mason JB (2003) Biochemical and molecular aberrations in the rat colon due to folate depletion are age-specific. J Nutr 133:1206–1212
Christman JK, Sheikhnejad G, Dizik M, Abileah S, Wainfan E (1993) Reversibility of changes in nucleic-acid methylation and gene-expression induced in rat-liver by severe dietary methyl deficiency. Carcinogenesis 14:551–557
Chuang SC, Stolzenberg-Solomon R, Ueland PM, Vollset SE, Midttun O, Olsen A, Tjonneland A, Overvad K, Boutron-Ruault MC, Morois S, Clavel-Chapelon F, Teucher B, Kaaks R, Weikert C, Boeing H, Trichopoulou A, Benetou V, Naska A, Jenab M, Slimani N, Romieu I, Michaud DS, Palli D, Sieri S, Panico S, Sacerdote C, Tumino R, Skeie G, Duell EJ, Rodriguez L, Molina-Montes E, Huerta JM, Larranaga N, Gurrea AB, Johansen D, Manjer J, Ye WM, Sund M, Peeters PHM, Jeurnink S, Wareham N, Khaw KT, Crowe F, Riboli E, Bueno-de-Mesquita B, Vineis P (2011) A U-shaped relationship between plasma folate and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition. Eur J Cancer 47:1808–1816
Ciappio ED, Liu Z, Brooks RS, Mason JB, Bronson RT, Crott JW (2011a) Maternal B vitamin supplementation from preconception through weaning suppresses intestinal tumorigenesis in Apc(1638N) mouse offspring. Gut 60:1695–1702
Ciappio ED, Mason JB, Crott JW (2011b) Maternal one-carbon nutrient intake and cancer risk in offspring. Nutr Rev 69:561–571
Clarke R, Halsey J, Lewington S, Lonn E, Armitage J, Manson JE, Bonaa KH, Spence JD, Nygard O, Jamison R, Gaziano JM, Guarino P, Bennett D, Mir F, Peto R, Collins R (2010) Effects of lowering homocysteine levels with B vitamins on cardiovascular disease, cancer, and cause-specific mortality: meta-analysis of 8 randomized trials involving 37 485 individuals. Arch Intern Med 170:1622–1631
Colapinto CK, O’Connor DL, Tremblay MS (2011) Folate status of the population in the Canadian Health Measures Survey. CMAJ 183:E100–E106
Cole BF, Baron JA, Sandler RS, Haile RW, Ahnen DJ, Bresalier RS, McKeown-Eyssen G, Summers RW, Rothstein RI, Burke CA, Snover DC, Church TR, Allen JI, Robertson DJ, Beck GJ, Bond JH, Byers T, Mandel JS, Mott LA, Pearson LH, Barry EL, Rees JR, Marcon N, Saibil F, Ueland PM, Greenberg ER (2007) Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA 297:2351–2359
Collin SM, Metcalfe C, Refsum H, Lewis SJ, Zuccolo L, Smith GD, Chen L, Harris R, Davis M, Marsden G, Johnston C, Lane JA, Ebbing M, Bonaa KH, Nygard O, Ueland PM, Grau MV, Baron JA, Donovan JL, Neal DE, Hamdy FC, Smith AD, Martin RM (2010) Circulating folate, vitamin B12, homocysteine, vitamin B12 transport proteins, and risk of prostate cancer: a case-control study, systematic review, and meta-analysis. Cancer Epidemiol Biomarkers Prev 19:1632–1642
Couvert P, Carrie A, Du Montcel ST, Vaysse J, Sutton A, Barget N, Trinchet J-C, Beaugrand M, Ganne N, Giral P, Chelly J (2012) Insulin-like growth factor 2 gene methylation in peripheral blood mononuclear cells of patients with hepatitis C related cirrhosis or hepatocellular carcinoma. Clin Res Hepatol Gastroenterol 36:345–351
Cravo M, Fidalgo P, Pereira AD, Gouveia-Oliveira A, Chaves P, Selhub J, Mason JB, Mira FC, Leitao CN (1994) DNA methylation as an intermediate biomarker in colorectal cancer: modulation by folic acid supplementation. Eur J Cancer Prev 3:473–479
Cravo ML, Albuquerque CM, Salazar De Sousa L, Gloria LM, Chaves P, Dias Pereira A, Nobre Leitao C, Quina MG, Costa Mira F (1998a) Microsatellite instability in non-neoplastic mucosa of patients with ulcerative colitis: effect of folate supplementation. Am J Gastroenterol 93:2060–2064
Cravo ML, Pinto AG, Chaves P, Cruz JA, Lage P, Nobre Leitao C, Costa Mira F (1998b) Effect of folate supplementation on DNA methylation of rectal mucosa in patients with colonic adenomas: correlation with nutrient intake. Clin Nutr 17:45–49
Crider KS, Bailey LB, Berry RJ (2011) Folic acid food fortification-its history, effect, concerns, and future directions. Nutrients 3
Cropley JE, Suter CM, Beckman KB, Martin DIK (2006) Germ-line epigenetic modification of the murine A(vy) allele by nutritional supplementation. Proc Natl Acad Sci U S A 103:17308–17312
Crott JW, Liu Z, Keyes MK, Choi S-W, Jang H, Moyer MP, Mason JB (2008) Moderate folate depletion modulates the expression of selected genes involved in cell cycle, intracellular signaling and folate uptake in human colonic epithelial cell lines. J Nutr Biochem 19:328–335
Crowell J, Ly A, Kim YI (2011) Folate and DNA methylation. In: Maulik N, Maulik G (eds) Nutrition, epigenetic mechanisms, and human disease. CRC, Boca Raton
Curtin K, Slattery ML, Ulrich CM, Bigler J, Levin TR, Wolff RK, Albertsen H, Potter JD, Samowitz WS (2007) Genetic polymorphisms in one-carbon metabolism: associations with CpG island methylator phenotype (CIMP) in colon cancer and the modifying effects of diet. Carcinogenesis 28:1672–1679
Dahlin AM, Van Guelpen B, Hultdin J, Johansson I, Hallmans G, Palmqvist R (2008) Plasma vitamin B12 concentrations and the risk of colorectal cancer: a nested case-referent study. Int J Cancer 122:2057–2061
Davis CD, Uthus EO (2004) DNA methylation, cancer susceptibility, and nutrient interactions. Exp Biol Med 229:988–995
De Vogel S, Bongaerts BW, Wouters KA, Kester AD, Schouten LJ, De Goeij AF, De Bruine AP, Goldbohm RA, Van Den Brandt PA, Van Engeland M, Weijenberg MP (2008a) Associations of dietary methyl donor intake with MLH1 promoter hypermethylation and related molecular phenotypes in sporadic colorectal cancer. Carcinogenesis 29:1765–1773
De Vogel S, Dindore V, Van Engeland M, Goldbohm RA, Van Den Brandt PA, Weijenberg MP (2008b) Dietary folate, methionine, riboflavin, and vitamin B-6 and risk of sporadic colorectal cancer. J Nutr 138:2372–2378
De Vogel S, Schneede J, Ueland PM, Vollset SE, Meyer K, Fredriksen A, Midttun O, Bjorge T, Kampman E, Bretthauer M, Hoff G (2011a) Biomarkers related to one-carbon metabolism as potential risk factors for distal colorectal adenomas. Cancer Epidemiol Biomarkers Prev 20:1726–1735
De Vogel S, Wouters KAD, Gottschalk RWH, Van Schooten FJ, De Goeij AFPM, De Bruine AP, Goldbohm RA, Van Den Brandt PA, Van Engeland M, Weijenberg MP (2011b) Dietary methyl donors, methyl metabolizing enzymes, and epigenetic regulators: diet-gene interactions and promoter CpG island hypermethylation in colorectal cancer. Cancer Causes Control 22:1–12
De Wals P, Tairou F, Van Allen MI, Uh SH, Lowry RB, Sibbald B, Evans JA, Van Den Hof MC, Zimmer P, Crowley M, Fernandez B, Lee NS, Niyonsenga T (2007) Reduction in neural-tube defects after folic acid fortification in Canada. N Engl J Med 357:135–142
Dizik M, Christman JK, Wainfan E (1991) Alterations in expression and methylation of specific genes in livers of rats fed a cancer promoting methyl-deficient diet. Carcinogenesis 12:1307–1312
Dockerty JD, Herbison P, Skegg DC, Elwood M (2007) Vitamin and mineral supplements in pregnancy and the risk of childhood acute lymphoblastic leukaemia: a case-control study. BMC Public Health 7:136
Dominguez-Salas P, Cox SE, Prentice AM, Hennig BJ, Moore SE (2012) Maternal nutritional status, C-1 metabolism and offspring DNA methylation: a review of current evidence in human subjects. Proc Nutr Soc 71:154–165
Du YP, Peng JS, Sun A, Tang ZH, Ling WH, Zhu HL (2009) Assessment of the effect of betaine on p16 and c-myc DNA methylation and mRNA expression in a chemical induced rat liver cancer model. BMC Cancer 9
Duthie SJ, Narayanan S, Blum S, Pirie L, Brand GM (2000) Folate deficiency in vitro induces uracil misincorporation and DNA hypomethylation and inhibits DNA excision repair in immortalized normal human colon epithelial cells. Nutr Cancer 37:245–251
Duthie SJ, Grant G, Pirie LP, Watson AJ, Margison GP (2010) Folate deficiency alters hepatic and colon MGMT and OGG-1 DNA repair protein expression in rats but has no effect on genome-wide DNA methylation. Cancer Prev Res (Phila) 3:92–100
Ebbing M, Bonaa KH, Nygard O, Arnesen E, Ueland PM, Nordrehaug JE, Rasmussen K, Njolstad I, Refsum H, Nilsen DW, Tverdal A, Meyer K, Vollset SE (2009) Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA 302:2119–2126
Ebbing M, Bonaa KH, Arnesen E, Ueland PM, Nordrehaug JE, Rasmussen K, Njolstad I, Nilsen DW, Refsum H, Tverdal A, Vollset SE, Schirmer H, Bleie O, Steigen T, Midttun O, Fredriksen A, Pedersen ER, Nygard O (2010) Combined analyses and extended follow-up of two randomized controlled homocysteine-lowering B-vitamin trials. J Intern Med 268:367–382
Egger G, Liang G, Aparicio A, Jones PA (2004) Epigenetics in human disease and prospects for epigenetic therapy. Nature 429:457–463
Esteller M (2003) Relevance of DNA methylation in the management of cancer. Lancet Oncol 4:351–358
Esteller M (2007) Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet 8:286–298
Esteller M (2012) Human cancer epigenetics. Eur J Cancer 48:S6
Eussen SJPM, Vollset SE, Hustad S, Midttun O, Meyer K, Fredriksen A, Ueland PM, Jenab M, Slimani N, Boffetta P, Overvad K, Thorlacius-Ussing O, Tjonneland A, Olsen A, Clavel-Chapelon F, Boutron-Ruault M-C, Morois S, Weikert C, Pischon T, Linseisen J, Kaaks R, Trichopoulou A, Zilis D, Katsoulis M, Palli D, Pala V, Vineis P, Tumino R, Panico S, Peeters PHM, Bueno-De-Mesquita HB, Van Duijnhoven FJB, Skeie G, Munoz X, Martinez C, Dorronsoro M, Ardanaz E, Navarro C, Rodriguez L, Vanguelpen B, Palmqvist R, Manjer J, Ericson U, Bingham S, Khaw K-T, Norat T, Riboli E (2010a) Plasma vitamins B2, B6, and B12, and related genetic variants as predictors of colorectal cancer risk. Cancer Epidemiol Biomarkers Prev 19:2549–2561
Eussen SJPM, Vollset SE, Hustad S, Midttun O, Meyer K, Fredriksen A, Ueland PM, Jenab M, Slimani N, Ferrari P, Agudo A, Sala N, Capella G, Del Giudice G, Palli D, Boeing H, Weikert C, Bueno-De-Mesquita HB, Buechner FL, Carneiro F, Berrino F, Vineis P, Tumino R, Panico S, Berglund G, Manjer J, Stenling R, Hallmans G, Martinez C, Arrizola L, Barricarte A, Navarro C, Rodriguez L, Bingham S, Linseisen J, Kaaks R, Overvad K, Tjonneland A, Peeters PHM, Numans ME, Clavel-Chapelon F, Boutron-Ruault M-C, Morois S, Trichopoulou A, Lund E, Plebani M, Riboli E, Gonzalez CA (2010b) Vitamins B2 and B6 and genetic polymorphisms related to one-carbon metabolism as risk factors for gastric adenocarcinoma in the European prospective investigation into cancer and nutrition. Cancer Epidemiol Biomarkers Prev 19:28–38
Fang JY, Xiao SD, Zhu SS, Yuan JM, Qiu DK, Jiang SJ (1997) Relationship of plasma folic acid and status of DNA methylation in human gastric cancer. J Gastroenterol 32:171–175
Fearon ER (2011) Molecular genetics of colorectal cancer. Annu Rev Pathol 6:479–507
Feigelson HS, Jonas CR, Robertson AS, McCollough ML, Thun MJ, Calle EE (2003) Alcohol, folate, methionine, and risk of incident breast cancer in the American Cancer Society Cancer Prevention Study II Nutrition Cohort. Cancer Epidemiol Biomarkers Prev 12:161–164
Felix AS, Weissfeld JL, Stone RA, Bowser R, Chivukula M, Edwards RP, Linkov F (2010) Factors associated with Type I and Type II endometrial cancer. Cancer Causes Control 21:1851–1856
Fenech M, Aitken C, Rinaldi J (1998) Folate, vitamin B12, homocysteine status and DNA damage in young Australian adults. Carcinogenesis 19:1163–1171
Fife J, Raniga S, Hider PN, Frizelle FA (2011) Folic acid supplementation and colorectal cancer risk: a meta-analysis. Colorectal Dis 13:132–137
Figueiredo JC, Grau MV, Haile RW, Sandler RS, Summers RW, Bresalier RS, Burke CA, McKeown-Eyssen GE, Baron JA (2009a) Folic acid and risk of prostate cancer: results from a randomized clinical trial. J Natl Cancer Inst 101:432–435
Figueiredo JC, Grau MV, Wallace K, Levine AJ, Shen L, Hamdan R, Chen X, Bresalier RS, McKeown-Eyssen G, Haile RW, Baron JA, Issa J-PJ (2009b) Global DNA hypomethylation (LINE-1) in the normal colon and lifestyle characteristics and dietary and genetic factors. Cancer Epidemiol Biomarkers Prev 18:1041–1049
Figueiredo JC, Mott LA, Giovannucci E, Wu K, Cole B, Grainge MJ, Logan RF, Baron JA (2011) Folic acid and prevention of colorectal adenomas: a combined analysis of randomized clinical trials. Int J Cancer 129:192–203
Finnell RH, Spiegelstein O, Wlodarczyk B, Triplett A, Pogribny IP, Melnyk S, James JS (2002) DNA methylation in Folbp1 knockout mice supplemented with folic acid during gestation. J Nutr 132:2457S–2461S
Fischer LM, Dacosta KA, Kwock L, Stewart PW, Lu TS, Stabler SP, Allen RH, Zeisel SH (2007) Sex and menopausal status influence human dietary requirements for the nutrient cholin. Am J Clin Nutr 85:1275–1285
Fisher AG, Brockdorff N (2012) Epigenetic memory and parliamentary privilege combine to evoke discussions on inheritance. Development 139:3891–3896
Flatley JE, McNeir K, Balasubramani L, Tidy J, Stuart EL, Young TA, Powers HJ (2009) Folate status and aberrant DNA methylation are associated with HPV infection and cervical pathogenesis. Cancer Epidemiol Biomarkers Prev 18:2782–2789
Forman D, Burley VJ (2006) Gastric cancer: global pattern of the disease and an overview of environmental risk factors. Best Pract Res Clin Gastroenterol 20:633–649
Friso S, Choi SW, Girelli D, Mason JB, Dolnikowski GG, Bagley PJ, Olivieri O, Jacques PF, Rosenberg IH, Corrocher R, Selhub J (2002) A common mutation in the 5,10-methylenetetrahydrofolate reductase gene affects genomic DNA methylation through an interaction with folate status. Proc Natl Acad Sci U S A 99:5606–5611
Friso S, Girelli D, Trabetti E, Olivieri O, Guarini P, Pignatti PF, Corrocher R, Choi SW (2005) The MTHFR 1298A > C polymorphism and genomic DNA methylation in human lymphocytes. Cancer Epidemiol Biomarkers Prev 14:938–943
Fryer AA, Nafee TM, Ismail KM, Carroll WD, Emes RD, Farrell WE (2009) LINE-1 DNA methylation is inversely correlated with cord plasma homocysteine in man: a preliminary study. Epigenetics 4:394–398
Fryer AA, Emes RD, Ismail KM, Haworth KE, Mein C, Carroll WD, Farrell WE (2011) Quantitative, high-resolution epigenetic profiling of CpG loci identifies associations with cord blood plasma homocysteine and birth weight in humans. Epigenetics 6
Fujimori S, Gudis K, Takahashi Y, Kotoyori M, Tatsuguchi A, Ohaki Y, Sakamoto C (2011) Determination of the minimal essential serum folate concentration for reduced risk of colorectal adenoma. Clin Nutr 30:653–658
Galvan-Portillo MV, Cantoral A, Onate-Ocana LF, Chen J, Herrera-Goepfert R, Torres-Sanchez L, Hernandez-Ramirez RU, Palma-Coca O, Lopez-Carrillo L (2009) Gastric cancer in relation to the intake of nutrients involved in one-carbon metabolism among MTHFR 677 TT carriers. Eur J Nutr 48:269–276
Galvan-Portillo MV, Onate-Ocana LF, Perez-Perez GI, Chen J, Herrera-Goepfert R, Chihu-Amparan L, Flores-Luna L, Mohar-Betancourt A, Lopez-Carrillo L (2010) Dietary folate and vitamin B12 intake before diagnosis decreases gastric cancer mortality risk among susceptible MTHFR 677TT carriers. Nutrition 26:201–208
Gao S, Ding LH, Wang JW, Li CB, Wang ZY (2013) Diet folate, DNA methylation and polymorphisms in methylenetetrahydrofolate reductase in association with the susceptibility to gastric cancer. Asian Pac J Cancer Prev 14:299–302
Ghosh C, Baker JA, Moysich KB, Rivera R, Brasure JR, McCann SE (2008) Dietary intakes of selected nutrients and food groups and risk of cervical cancer. Nutr Cancer 60:331–341
Ghoshal K, Li X, Datta J, Bai S, Pogribny I, Pogribny M, Huang Y, Young D, Jacob ST (2006) A folate- and methyl-deficient diet alters the expression of DNA methyltransferases and methyl CpG binding proteins involved in epigenetic gene silencing in livers of F344 rats. J Nutr 136:1522–1527
Gibson TM, Weinstein SJ, Pfeiffer RM, Hollenbeck AR, Subar AF, Schatzkin A, Mayne ST, Stolzenberg-Solomon R (2011) Pre- and postfortification intake of folate and risk of colorectal cancer in a large prospective cohort study in the United States. Am J Clin Nutr 94:1053–1062
Giovannucci E, Rimm EB, Ascherio A, Stampfer MJ, Colditz GA, Willett WC (1995) Alcohol, low-methionine–low-folate diets, and risk of colon cancer in men. J Natl Cancer Inst 87:265–273
Giovannucci E, Stampfer MJ, Colditz GA, Hunter DJ, Fuchs C, Rosner BA, Speizer FE, Willett WC (1998) Multivitamin use, folate, and colon cancer in women in the Nurses’ Health Study. Ann Intern Med 129:517–524
Gonda TA, Kim YI, Salas MC, Gamble MV, Shibata W, Muthupalani S, Sohn KJ, Abrams JA, Fox JG, Wang TC, Tycko B (2012) Folic acid increases global DNA methylation and reduces inflammation to prevent helicobacter-associated gastric cancer in mice. Gastroenterology 142:824–833
Gong Z, Holly EA, Bracci PM (2009) Intake of folate, vitamins B6, B12 and methionine and risk of pancreatic cancer in a large population-based case-control study. Cancer Causes Control 20:1317–1325
Goodman MT, McDuffie K, Hernandez B, Wilkens LR, Selhub J (2000) Case-control study of plasma folate, homocysteine, vitamin B-12, and cysteine as markers of cervical dysplasia. Cancer 89:376–382
Goodman MT, McDuffie K, Hernandez B, Wilkens LR, Bertram CC, Killeen J, Le Marchand L, Selhub J, Murphy S, Donlon TA (2001) Association of methylenetetrahydrofolate reductase polymorphism C677T and dietary folate with the risk of cervical dysplasia. Cancer Epidemiol Biomarkers Prev 10:1275–1280
Haas GP, Delongchamps N, Brawley OW, Wang CY, De La Roza G (2008) The worldwide epidemiology of prostate cancer: perspectives from autopsy studies. Can J Urol 15:3866–3871
Haggarty P, Hoad G, Campbell DM, Horgan GW, Piyathilake C, McNeill G (2013) Folate in pregnancy and imprinted gene and repeat element methylation in the offspring. Am J Clin Nutr 97:94–99
Hajizadeh B, Jessri M, Akhoondan M, Moasheri SM, Rashidkhani B (2012) Nutrient patterns and risk of esophageal squamous cell carcinoma: a case-control study. Dis Esophagus 25:442–448
Hanna L, Adams M (2006) Prevention of ovarian cancer. Best Prac Res Clin Obstet Gynaecol 20:339–362
Hariharan D, Saied A, Kocher HM (2008) Analysis of mortality rates for pancreatic cancer across the world. HPB 10:58–62
Harnack L, Jacobs DR, Nicodemus K, Lazovich D, Anderson K, Folsom AR (2002) Relationship of folate, vitamin B-6, vitamin B-12, and methionine intake to incidence of colorectal cancers. Nutr Cancer 43:152–158
Harris HR, Cramer DW, Vitonis AF, Depari M, Terry KL (2012) Folate, vitamin B6, vitamin B12, methionine and alcohol intake in relation to ovarian cancer risk. Int J Cancer 131:E518–E529
Heichman KA, Warren JD (2012) DNA methylation biomarkers and their utility for solid cancer diagnostics. Clin Chem Lab Med 50:1707–1721
Herman JG, Baylin SB (2003) Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med 349:2042–2054
Hernandez BY, McDuffie K, Wilkens LR, Kamemoto L, Goodman MT (2003) Diet and premalignant lesions of the cervix: evidence of a protective role for folate, riboflavin, thiamin, and vitamin B-12. Cancer Causes Control 14:859–870
Hezel AF, Kimmelman AC, Stanger BZ, Bardeesy N, Depinho RA (2006) Genetics and biology of pancreatic ductal adenocarcinoma. Genes Dev 20:1218–1249
Hirsch S, Sanchez H, Albala C, De La Maza MP, Barrera G, Leiva L, Bunout D (2009) Colon cancer in Chile before and after the start of the flour fortification program with folic acid. Eur J Gastroenterol Hepatol 21:436–439
Ho E, Beaver LM, Williams DE, Dashwood RH (2011) Dietary factors and epigenetic regulation for prostate cancer prevention. Adv Nutr 2:497–510
Holm K, Hegardt C, Staaf J, Vallon-Christersson J, Jonsson G, Olsson H, Borg A, Ringner M (2010) Molecular subtypes of breast cancer are associated with characteristic DNA methylation patterns. Breast Cancer Res 12:R36
Honda S, Arai Y, Haruta M, Sasaki F, Ohira M, Yamaoka H, Horie H, Nakagawara A, Hiyama E, Todo S, Kaneko Y (2008) Loss of imprinting of IGF2 correlates with hypermethylation of the H19 differentially methylated region in hepatoblastoma. Br J Cancer 99:1891–1899
Hou L, Wang H, Sartori S, Gawron A, Lissowska J, Bollati V, Tarantini L, Zhang FF, Zatonski W, Chow W-H, Baccarelli A (2010) Blood leukocyte DNA hypomethylation and gastric cancer risk in a high-risk Polish population. Int J Cancer 127:1866–1874
Hoyo C, Murtha AP, Schildkraut JM, Jirtle RL, Demark-Wahnefried W, Forman MR, Iversen ES, Kurtzberg J, Overcash F, Huang Z, Murphy SK (2011) Methylation variation at IGF2 differentially methylated regions and maternal folic acid use before and during pregnancy. Epigenetics 6:928–936
Huang M, Chen H (2008) Effect of folate deprivation on WNT signaling pathway in human colon cell lines. FASEB J 22
Hultdin J, Van Guelpen B, Bergh A, Hallmans G, Stattin M (2005) Plasma folate, vitamin B12, and homocysteine and prostate cancer risk: a prospective study. Int J Cancer 113:819–824
Ibiebele TI, Hughes MC, Pandeya N, Zhao Z, Montgomery G, Hayward N, Green AC, Whiteman DC, Webb PM, Study of Digestive Health, Australian Cancer Study (2011) High intake of folate from food sources is associated with reduced risk of esophageal cancer in an Australian population. J Nutr 141:274–283
Ibrahim EM, Zekri JM (2010) Folic acid supplementation for the prevention of recurrence of colorectal adenomas: metaanalysis of interventional trials. Med Oncol 27:915–918
Ingrosso D, Cimmino A, Perna AF, Masella L, De Santo NG, De Bonis ML, Vacca M, D’esposito M, D’urso M, Galletti P, Zappia V (2003) Folate treatment and unbalanced methylation and changes of allelic expression induced by hyperhomocysteinaemia in patients with uraemia. Lancet 361:1693–1699
Issa JP (2004) CpG island methylator phenotype in cancer. Nat Rev Cancer 4:988–993
Jacob RA, Gretz DM, Taylor PC, James SJ, Pogribny IP, Miller BJ, Henning SM, Swendseid ME (1998) Moderate folate depletion increases plasma homocysteine and decreases lymphocyte DNA methylation in postmenopausal women. J Nutr 128:1204–1212
Jacobs EJ, Connell CJ, Patel AV, Chao A, Rodriguez C, Seymour J, McCullough ML, Calle EE, Thun MJ (2001) Multivitamin use and colon cancer mortality in the Cancer Prevention Study II cohort (United States). Cancer Causes Control 12:927–934
Jain MG, Rohan TE, Howe GR, Miller AB (2000) A cohort study of nutritional factors and endometrial cancer. Eur J Epidemiol 16:899–905
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
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90
Jeronimo C, Bastian PJ, Bjartell A, Carbone GM, Catto JW, Clark SJ, Henrique R, Nelson WG, Shariat SF (2011) Epigenetics in prostate cancer: biologic and clinical relevance. Eur Urol 60:753–766
Jessri M, Rashidkhani B, Hajizadeh B, Jessri M, Gotay C (2011) Macronutrients, vitamins and minerals intake and risk of esophageal squamous cell carcinoma: a case-control study in Iran. Nutr J 10
Jin F, Qu LS, Shen XZ (2009) Association between the methylenetetrahydrofolate reductase C677T polymorphism and hepatocellular carcinoma risk: a meta-analysis. Diagn Pathol 4:39
Johansson M, Appleby PN, Allen NE, Travis RC, Roddam AW, Egevad L, Jenab M, Rinaldi S, Kiemeney LA, Bueno-De-Mesquita HB, Vollset SE, Ueland PM, Sanchez MJ, Quiros JR, Gonzalez CA, Larranaga N, Chirlaque MD, Ardanaz E, Sieri S, Palli D, Vineis P, Tumino R, Linseisen J, Kaaks R, Boeing H, Pischon T, Psaltopoulou T, Trichopoulou A, Trichopoulos D, Khaw KT, Bingham S, Hallmans G, Riboli E, Stattin P, Key TJ (2008) Circulating concentrations of folate and vitamin B12 in relation to prostate cancer risk: results from the European Prospective Investigation into Cancer and Nutrition study. Cancer Epidemiol Biomarkers Prev 17:279–285
Johansson M, Van Guelpen B, Vollset SE, Hultdin J, Bergh A, Key T, Midttun O, Hallmans G, Ueland PM, Stattin P (2009) One-carbon metabolism and prostate cancer risk: prospective investigation of seven circulating B vitamins and metabolites. Cancer Epidemiol Biomarkers Prev 18:1538–1543
Jones PA, Baylin SB (2002) The fundamental role of epigenetic events in cancer. Nat Rev Genet 3:415–428
Jones PA, Buckley JD (1990) The role of DNA methylation in cancer. Adv Cancer Res 54:1–23
Jones PL, Veenstra GJ, Wade PA, Vermaak D, Kass SU, Landsberger N, Strouboulis J, Wolffe AP (1998) Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat Genet 19:187–191
Jun Ying MHR, Michael Hallman D, Hernandez LM, Spitz MR, Forman MR, Gorlova OY (2013) Associations between dietary intake of choline and betaine and lung cancer risk. PLoS One 8:e54561
Kabat GC, Miller AB, Jain M, Rohan TE (2008) Dietary intake of selected B vitamins in relation to risk of major cancers in women. Br J Cancer 99:816–821
Kadaveru K, Protiva P, Greenspan EJ, Kim YI, Rosenberg DW (2012) Dietary methyl donor depletion protects against intestinal tumorigenesis in ApcMin/+ mice. Cancer Prev Res 5:911–920
Kane MF, Loda M, Gaida GM, Lipman J, Mishra R, Goldman H, Jessup JM, Kolodner R (1997) Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines. Cancer Res 57:808–811
Kasperzyk JL, Fall K, Mucci LA, Hakansson N, Wolk A, Johansson JE, Andersson SO, Andren O (2009) One-carbon metabolism-related nutrients and prostate cancer survival. Am J Clin Nutr 90:561–569
Kawakami K, Ruszkiewicz A, Bennett G, Moore J, Watanabe G, Iacopetta B (2003) The folate pool in colorectal cancers is associated with DNA hypermethylation and with a polymorphism in methylenetetrahydrofolate reductase. Clin Cancer Res 9:5860–5865
Kelemen LE, Sellers TA, Vierkant RA, Harnack L, Cerhan JR (2004) Association of folate and alcohol with risk of ovarian cancer in a prospective study of postmenopausal women. Cancer Causes Control 15:1085–1093
Kennedy DA, Stern SJ, Moretti M, Matok I, Sarkar M, Nickel C, Koren G (2011) Folate intake and the risk of colorectal cancer: a systematic review and meta-analysis. Cancer Epidemiol 35:2–10
Keszei AP, Verhage BA, Heinen MM, Goldbohm RA, Van Den Brandt PA (2009) Dietary folate and folate vitamers and the risk of pancreatic cancer in the Netherlands cohort study. Cancer Epidemiol Biomarkers Prev 18:1785–1791
Key TJA, Silcocks PB, Davey GK, Appleby PN, Bishop DT (1997) A case-control study of diet and prostate cancer. Br J Cancer 76:678–687
Key T, Schatzkin A, Willett WC, Allen NE, Spencer EA, Travis RC (2004) Diet, nutrition and the prevention of cancer. Public Health Nutr 7:187–200
Key TJ, Appleby PN, Masset G, Brunner EJ, Cade JE, Greenwood DC, Stephen AM, Kuh D, Bhaniani A, Powell N, Khaw K-T (2012) Vitamins, minerals, essential fatty acids and colorectal cancer risk in the United Kingdom Dietary Cohort Consortium. Int J Cancer 131:E320–E325
Khosraviani K, Weir HP, Hamilton P, Moorehead J, Williamson K (2002) Effect of folate supplementation on mucosal cell proliferation in high risk patients for colon cancer. Gut 51:195–199
Kim YI (1999) Folate and carcinogenesis: evidence, mechanisms, and implications. J Nutr Biochem 10:66–88
Kim YI (2003) Role of folate in colon cancer development and progression. J Nutr 133:3731S–3739S
Kim YI (2004a) Folate and DNA methylation: a mechanistic link between folate deficiency and colorectal cancer? Cancer Epidemiol Biomarkers Prev 13:511–519
Kim YI (2004b) Will mandatory folic acid fortification prevent or promote cancer? Am J Clin Nutr 80:1123–1128
Kim YI (2005) Nutritional epigenetics: impact of folate deficiency on DNA methylation and colon cancer susceptibility. J Nutr 135:2703–2709
Kim YI (2006) Folate: a magic bullet or a double edged sword for colorectal cancer prevention? Gut 55:1387–1389
Kim YI (2007a) Folate and colorectal cancer: an evidence-based critical review. Mol Nutr Food Res 51:267–292
Kim YI (2007b) Folic acid fortification and supplementation—good for some but not so good for others. Nutr Rev 65:504–511
Kim YI (2008) Folic acid supplementation and cancer risk: point. Cancer Epidemiol Biomarkers Prev 17:2220–2225
Kim YI (2009) Role of the MTHFR polymorphisms in cancer risk modification and treatment. Future Oncol 5:523–542
Kim YI, Giuliano A, Hatch KD, Schneider A, Nour MA, Dallal GE, Selhub J, Mason JB (1994) Global DNA hypomethylation increases progressively in cervical dysplasia and carcinoma. Cancer 74:893–899
Kim YI, Salomon RN, Graeme-Cook F, Choi SW, Smith DE, Dallal GE, Mason JB (1996) Dietary folate protects against the development of macroscopic colonic neoplasia in a dose responsive manner in rats. Gut 39:732–740
Kim YI, Pogribny IP, Basnakian AG, Miller JW, Selhub J, James SJ, Mason JB (1997) Folate deficiency in rats induces DNA strand breaks and hypomethylation within the p53 tumor suppressor gene. Am J Clin Nutr 65:46–52
Kim YI, Baik HW, Fawaz K, Knox T, Lee YM, Norton R, Libby E, Mason JB (2001) Effects of folate supplementation on two provisional molecular markers of colon cancer: a prospective, randomized trial. Am J Gastroenterol 96:184–195
Kim TH, Yang J, Darling PB, O’Connor DL (2004) A large pool of available folate exists in the large intestine of human infants and piglets. J Nutr 134:1389–1394
Kim DH, Smith-Warner SA, Spiegelman D, Yaun SS, Colditz GA, Freudenheim JL, Giovannucci E, Goldbohm RA, Graham S, Harnack L, Jacobs EJ, Leitzmann M, Mannisto S, Miller AB, Potter JD, Rohan TE, Schatzkin A, Speizer FE, Stevens VL, Stolzenberg-Solomon R, Terry P, Toniolo P, Weijenberg MP, Willett WC, Wolk A, Zeleniuch-Jacquotte A, Hunter DJ (2010) Pooled analyses of 13 prospective cohort studies on folate intake and colon cancer. Cancer Causes Control 21:1919–1930
Kim HW, Kim KN, Choi YJ, Chang N (2013) Effects of paternal folate deficiency on the expression of insulin-like growth factor-2 and global DNA methylation in the fetal brain. Mol Nutr Food Res 57(4):671–676
Klaus A, Birchmeier W (2008) Wnt signalling and its impact on development and cancer. Nat Rev Cancer 8:387–398
Klose RJ, Bird AP (2006) Genomic DNA methylation: the mark and its mediators. Trends Biochem Sci 31:89–97
Kobayashi LC, Limburg H, Miao Q, Woolcott C, Bedard LL, Massey TE, Aronson KJ (2012) Folate intake, alcohol consumption, and the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism: influence on prostate cancer risk and interactions. Front Oncol 2:100
Kotsopoulos J, Sohn KJ, Martin R, Choi M, Renlund R, McKerlie C, Hwang SW, Medline A, Kim YIJ (2003) Dietary folate deficiency suppresses N-methyl-N-nitrosourea-induced mammary tumorigenesis in rats. Carcinogenesis 24:937–944
Kotsopoulos J, Medline A, Renlund R, Sohn KJ, Martin R, Hwang SW, Lu S, Archer MC, Kim YI (2005) Effects of dietary folate on the development and progression of mammary tumors in rats. Carcinogenesis 26:1603–1612
Kotsopoulos J, Sohn KJ, Kim YI (2008) Postweaning dietary folate deficiency provided through childhood to puberty permanently increases genomic DNA methylation in adult rat liver. J Nutr 138:703–709
Kotsopoulos J, Hankinson SE, Tworoger SS (2010) Dietary betaine and choline intake are not associated with risk of epithelial ovarian cancer. Eur J Clin Nutr 64:111–114
Kotsopoulos J, Kim YI, Narod SA (2012) Folate and breast cancer: what about high-risk women? Cancer Causes Control 23:1405–1420
Kovacheva VP, Mellott TJ, Davison JM, Wagner N, Lopez-Coviella I, Schnitzler AC, Blusztajn JK (2007) Gestational choline deficiency causes global and Igf2 gene DNA hypermethylation by up-regulation of dnmt1 expression. J Biol Chem 282:31777–31788
Kovacheva VP, Davison JM, Mellott TJ, Rogers AE, Yang S, O’Brien MJ, Blusztajn JK (2009) Raising gestational choline intake alters gene expression in DMBA-evoked mammary tumors and prolongs survival. FASEB J 23:1054–1063
Kraunz KS, Hsiung D, McClean MD, Liu M, Osanyingbemi J, Nelson HH, Kelsey KT (2006) Dietary folate is associated with p16(INK4A) methylation in head and neck squamous cell carcinoma. Int J Cancer 119:1553–1557
Krishnaveni GV, Hill JC, Veena SR, Bhat DS, Wills AK, Karat CLS, Yajnik CS, Fall CHD (2009) Low plasma vitamin B-12 in pregnancy is associated with gestational ‘diabesity’ and later diabetes. Diabetologia 52:2350–2358
Kwanbunjan K, Saengkar P, Cheeramakara C, Tangjitgamol S, Chitcharoenrung K (2006) Vitamin B12 status of Thai women with neoplasia of the cervix uteri. Southeast Asian J Trop Med Public Health 37:178–183
Lajous M, Lazcano-Ponce E, Hernandez-Avila M, Willett W, Romieu I (2006a) Folate, vitamin B-6, and vitamin B-12 intake and the risk of breast cancer among Mexican women. Cancer Epidemiol Biomarkers Prev 15:443–448
Lajous M, Romieu I, Sabia S, Boutron-Ruault MC, Clavel-Chapelon F (2006b) Folate, vitamin B12 and postmenopausal breast cancer in a prospective study of French women. Cancer Causes Control 17:1209–1213
Lammi L, Arte S, Somer M, Jarvinen H, Lahermo P, Thesleff I, Pirinen S, Nieminen P (2004) Mutations in AXIN2 cause familial tooth agenesis and predispose to colorectal cancer. Am J Hum Genet 74:1043–1050
Larsson SC, Giovannucci E, Wolk A (2004) Dietary folate intake and incidence of ovarian cancer: The Swedish Mammography Cohort. J Natl Cancer Inst 96:396–402
Larsson SC, Giovannucci E, Wolk A (2006a) Folate intake, MTHFR polymorphisms, and risk of esophageal, gastric, and pancreatic cancer: a meta-analysis. Gastroenterology 131:1271–1283
Larsson SC, Hakansson N, Giovannucci E, Wolk A (2006b) Folate intake and pancreatic cancer incidence: a prospective study of Swedish women and men. J Natl Cancer Inst 98:407–413
Larsson SC, Orsini N, Wolk A (2010) Vitamin B6 and risk of colorectal cancer: a meta-analysis of prospective studies. JAMA 303:1077–1083
Lashner BA, Shapiro BD, Husain A, Goldblum JR (1999) Evaluation of the usefulness of testing for p53 mutations in colorectal cancer surveillance for ulcerative colitis. Am J Gastroenterol 94:456–462
Lawrance AK, Deng L, Rozen R (2009) Methylenetetrahydrofolate reductase deficiency and low dietary folate reduce tumorigenesis in Apcmin/+ mice. Gut 58:805–811
Lazarevic K, Nagorni A, Bogdanovic D, Rancic N, Stosic L, Milutinovic S (2011) Dietary micronutrients and gastric cancer: hospital based study. Central Eur J Med 6:783–787
Le Marchand L, Wang H, Selhub J, Vogt TM, Yokochi L, Decker R (2011) Association of plasma vitamin B6 with risk of colorectal adenoma in a multiethnic case-control study. Cancer Causes Control 22:929–936
Lee JE, Li H, Giovannucci E, Lee IM, Selhub J, Stampfer M, Ma J (2009) Prospective study of plasma vitamin B(6) and risk of colorectal cancer in men. Cancer Epidemiol Biomarkers Prev 18:1197–1202
Lee JE, Giovannucci E, Fuchs CS, Willett WC, Zeisel SH, Cho E (2010) Choline and betaine intake and the risk of colorectal cancer in men. Cancer Epidemiol Biomarkers Prev 19:884–887
Li E, Jaenisch R (2000) DNA methylation and methyltransferases. In: Ehrlich M (ed) DNA alterations in cancer: genetic and epigenetic changes. Eaton, Natick
Li XL, Xu JH (2012) MTHFR polymorphism and the risk of prostate cancer: a meta-analysis of case-control studies. Prostate Cancer Prostatic Dis 15:244–249
Li JY, Taylor PR, Li B, Dawsey S, Wang GQ, Ershow AG, Guo WD, Liu SF, Yang CS, Shen Q, Wang W, Mark SD, Zou XN, Greenwald P, Wu YP, Blot WJ (1993) Nutrition intervention trials in Linxian, China—multiple vitamin mineral supplementation, cancer incidence, and disease-specific mortality among adults with esophageal dysplasia. J Natl Cancer Inst 85:1492–1498
Lillycrop KA, Phillips ES, Jackson AA, Hanson MA, Burdge GC (2005) Dietary protein restriction of pregnant rats induces and folic acid supplementation prevents epigenetic modification of hepatic gene expression in the offspring. J Nutr 135:1382–1386
Lillycrop KA, Slater-Jefferies JL, Hanson MA, Godfrey KM, Jackson AA, Burdge GC (2007) Induction of altered epigenetic regulation of the hepatic glucocorticoid receptor in the offspring of rats fed a protein-restricted diet during pregnancy suggests that reduced DNA methyltransferase-1 expression is involved in impaired DNA methylation and changes in histone modifications. Br J Nutr 97:1064–1073
Lim U, Flood A, Choi SW, Albanes D, Cross AJ, Schatzkin A, Sinha R, Katki HA, Cash B, Schoenfeld P, Stolzenberg-Solomon R (2008) Genomic methylation of leukocyte DNA in relation to colorectal adenoma among asymptomatic women. Gastroenterology 134:47–55
Lin J, Lee IM, Cook NR, Selhub J, Manson JE, Buring JE, Zhang SM (2008) Plasma folate, vitamin B-6, vitamin B-12, and risk of breast cancer in women. Am J Clin Nutr 87:734–743
Lin PC, Giannopoulou EG, Park K, Mosquera JM, Sboner A, Tewari AK, Garraway LA, Beltran H, Rubin MA, Elemento O (2013) Epigenomic alterations in localized and advanced prostate cancer. Neoplasia 15:373–383
Linhart HG, Troen AM, Bell GW, Cantu E, Chao WH, Moran E, Steine E, He T, Jaenisch R (2009) Folate deficiency induces genomic uracil misincorporation and hypomethylation but does not increase DNA point mutations. Gastroenterology 136:227–235
Liu ZH, Ciappio ED, Crott JW, Brooks RS, Nesvet J, Smith DE, Choi SW, Mason JB (2011) Combined inadequacies of multiple B vitamins amplify colonic Wnt signaling and promote intestinal tumorigenesis in BAT-LacZ X Apc1638N mice. FASEB J 25:3136–3145
Liu WR, Shi YH, Peng YF, Fan J (2012) Epigenetics of hepatocellular carcinoma: a new horizon. Chin Med J (Engl) 125:2349–2360
Liu JJ, Hazra A, Giovannucci E, Hankinson SE, Rosner B, De Vivo I (2013) One-carbon metabolism factors and endometrial cancer risk. Br J Cancer 108:183–187
Logan CY, Nusse R (2004) The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 20:781–810
Lu C, Xie H, Wang F, Shen H, Wang J (2011) Diet folate, DNA methylation and genetic polymorphisms of MTHFR C677T in association with the prognosis of esophageal squamous cell carcinoma. BMC Cancer 11
Lubecka-Pietruszewska K, Kaufman-Szymczyk A, Stefanska B, Fabianowska-Majewska K (2013) Folic acid enforces DNA methylation-mediated transcriptional silencing of PTEN, APC and RARbeta2 tumour suppressor genes in breast cancer. Biochem Biophys Res Commun 430:623–628
Lucock M (2004) Is folic acid the ultimate functional food component for disease prevention? BMJ 328:211–214
Ly A, Lee H, Chen J, Sie KKY, Renlund R, Medline A, Sohn K-J, Croxford R, Thompson LU, Kim Y-I (2011) Effect of maternal and postweaning folic acid supplementation on mammary tumor risk in the offspring. Cancer Res 71:988–997
Ly A, Hoyt L, Crowell J, Kim Y-I (2012) Folate and DNA methylation. Antioxid Redox Signal 17:302–326
Ma E, Iwasaki M, Junko I, Hamada GS, Nishimoto IN, Carvalho SM, Motola J Jr, Laginha FM, Tsugane S (2009a) Dietary intake of folate, vitamin B6, and vitamin B12, genetic polymorphism of related enzymes, and risk of breast cancer: a case-control study in Brazilian women. BMC Cancer 9:122
Ma E, Iwasaki M, Kobayashi M, Kasuga Y, Yokoyama S, Onuma H, Nishimura H, Kusama R, Tsugane S (2009b) Dietary intake of folate, vitamin B2, vitamin B6, vitamin B12, genetic polymorphism of related enzymes, and risk of breast cancer: a case-control study in Japan. Nutr Cancer 61:447–456
Macfarlane AJ, Greene-Finestone LS, Shi YP (2011) Vitamin B-12 and homocysteine status in a folate-replete population: results from the Canadian Health Measures Survey. Am J Clin Nutr 94:1079–1087
Maloney CA, Hay SM, Rees WD (2007) Folate deficiency during pregnancy impacts on methyl metabolism without affecting global DNA methylation in the rat fetus. Br J Nutr 97:1090–1098
Malouf R, Grimley Evans J (2003) The effect of vitamin B6 on cognition. Cochrane Database Syst Rev CD004393
Markowitz SD, Bertagnolli MM (2009) Molecular origins of cancer: molecular basis of colorectal cancer. N Engl J Med 361:2449–2460
Marmot M, Atinmo T, Byers T, Chen J, Hirohata T, Jackson A, James W, Kolonel L, Kumanyika S, Leitzmann C (2007) Food, nutrition, physical activity, and the prevention of cancer: a global perspective. AICR, Washington, DC
Maruti SS, Ulrich CM, White E (2009) Folate and one-carbon metabolism nutrients from supplements and diet in relation to breast cancer risk. Am J Clin Nutr 89:624–633
Mason JB, Dickstein A, Jacques PF, Haggarty P, Selhub J, Dallal G, Rosenberg IH (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 Biomarkers Prev 16:1325–1329
Matthews RG, Haywood BJ (1979) Inhibition of pig liver methylenetetrahydrofolate reductase by dihydrofolate: some mechanistic and regulatory implications. Biochemistry 18:4845–4851
Mayne ST, Risch HA, Dubrow R, Chow WH, Gammon MD, Vaughan TL, Farrow DC, Schoenberg JB, Stanford JL, Ahsan H, West AB, Rotterdam H, Blot WJ, Fraumeni JF (2001) Nutrient intake and risk of subtypes of esophageal and gastric cancer. Cancer Epidemiol Biomarkers Prev 10:1055–1062
McCleary-Wheeler AL, Lomberk GA, Weiss FU, Schneider G, Fabbri M, Poshusta TL, Dusetti NJ, Baumgart S, Iovanna JL, Ellenrieder V, Urrutia R, Fernandez-Zapico ME (2013) Insights into the epigenetic mechanisms controlling pancreatic carcinogenesis. Cancer Lett 328:212–221
McKay JA, Waltham KJ, Williams EA, Mathers JC (2011a) Folate depletion during pregnancy and lactation reduces genomic DNA methylation in murine adult offspring. Genes Nutr 6:189–196
Mckay JA, Williams EA, Mathers JC (2011b) Effect of maternal and post-weaning folate supply on gene-specific DNA methylation in the small intestine of weaning and adult apc and wild type mice. Front Genet 2:23
McKay JA, Wong YK, Relton CL, Ford D, Mathers JC (2011c) Maternal folate supply and sex influence gene-specific DNA methylation in the fetal gut. Mol Nutr Food Res 55:1717–1723
McKay JA, Xie L, Harris S, Wong YK, Ford D, Mathers JC (2011d) Blood as a surrogate marker for tissue-specific DNA methylation and changes due to folate depletion in post-partum female mice. Mol Nutr Food Res 55:1026–1035
McKay JA, Groom A, Potter C, Coneyworth LJ, Ford D, Mathers JC, Relton CL (2012) Genetic and non-genetic influences during pregnancy on infant global and site specific DNA methylation: role for folate gene variants and vitamin B-12. PLoS One 7
Mellen M, Ayata P, Dewell S, Kriaucionis S, Heintz N (2012) MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system. Cell 151:1417–1430
Menezes CA, Bonde P, Bell Z, Swarbrick C, O’Hara G, Hoper M, Khosraviani K, Campbell FC, McGuigan J (2008) Folate supplementation in rats reduces gastro-esophageal reflux induced hyperproliferative esophagitis. Gastroenterology 134:A634
Michalek AM, Buck GM, Nasca PC, Freedman AN, Baptiste MS, Mahoney MC (1996) Gravid health status, medication use, and risk of neuroblastoma. Am J Epidemiol 143:996–1001
Milne E, Royle JA, Miller M, Bower C, De Klerk NH, Bailey HD, Van Bockxmeer F, Attia J, Scott RJ, Norris MD, Haber M, Thompson JR, Fritschi L, Marshall GM, Armstrong BK (2010) Maternal folate and other vitamin supplementation during pregnancy and risk of acute lymphoblastic leukemia in the offspring. Int J Cancer 126:2690–2699
Missaoui N, Hmissa S, Dante R, Frappart L (2010) Global DNA methylation in precancerous and cancerous lesions of the uterine cervix. Asian Pac J Cancer Prev 11:1741–1744
Mokarram P, Naghibalhossaini F, Saberi Firoozi M, Hosseini SV, Izadpanah A, Salahi H, Malek-Hosseini SA, Talei A, Mojallal M (2008) Methylenetetrahydrofolate reductase C677T genotype affects promoter methylation of tumor-specific genes in sporadic colorectal cancer through an interaction with folate/vitamin B12 status. World J Gastroenterol 14:3662–3671
Molloy AM, Kirke PN, Troendle JF, Burke H, Sutton M, Brody LC, Scott JM, Mills JM (2009) Maternal vitamin B12 status and risk of neural tube defects in a population with high neural tube defect prevalence and no folic acid fortification. Pediatrics 123:917–923
Morillon M, Katula K (2008) Alterations in Wnt signaling in folate deficient cells. FASEB J 22
MRC Vitamin Study Research Group (1991) Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet 338:131–137
Mu LN, Cao W, Zhang ZF, Yu SZ, Jiang QW, You NC, Lu QY, Zhou XF, Ding BG, Chang J, Chen CW, Wei GR, Cai L (2007) Polymorphisms of 5,10-methylenetetralydrofolate reductase (MTHFR), fruit and vegetable intake, and the risk of stomach cancer. Biomarkers 12:61–75
Nafee TM, Farrell WE, Carroll WD, Fryer AA, Ismail KMK (2008) Epigenetic control of fetal gene expression. BJOG 115:158–168
Nakai K, Mitomi H, Alkam Y, Arakawa A, Yao T, Tokuda E, Saito M, Kasumi F (2012) Predictive value of MGMT, hMLH1, hMSH2 and BRCA1 protein expression for pathological complete response to neoadjuvant chemotherapy in basal-like breast cancer patients. Cancer Chemother Pharmacol 69:923–930
Negri E, Lavecchia C, Franceschi S, Levi F, Parazzini F (1996) Intake of selected micronutrients and the risk of endometrial carcinoma. Cancer 77:917–923
Neuhouser ML, Nijhout HF, Gregory JF III, Reed MC, James SJ, Liu A, Shane B, Ulrich CM (2011) Mathematical modeling predicts the effect of folate deficiency and excess on cancer-related biomarkers. Cancer Epidemiol Biomarkers Prev 20:1912–1917
Nishisho I, Nakamura Y, Miyoshi Y, Miki Y, Ando H, Horii A, Koyama K, Utsunomiya J, Baba S, Hedge P, Markham A, Krush AJ, Petersen G, Hamilton SR, Nilbert MC, Levy DB, Bryan TM, Preisinger AC, Smith KJ, Su LK, Kinzler KW, Vogelstein B (1991) Mutations of chromosome-5Q21 genes in FAP and colorectal-cancer patients. Science 253:665–669
Oaks BM, Dodd KW, Meinhold CL, Jiao L, Church TR, Stolzenberg-Solomon RZ (2010) Folate intake, post-folic acid grain fortification, and pancreatic cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Am J Clin Nutr 91:449–455
Okabe K, Hayashi M, Yoshida I, Nishimura K, Fukushima N, Tsujiuchi T (2011) Distinct DNA methylation patterns of lysophosphatidic acid receptor genes during rat hepatocarcinogenesis induced by a choline-deficient L-amino acid-defined diet. Arch Toxicol 85:1303–1310
Olshan AF, Smith JC, Bondy ML, Neglia JP, Pollock BH (2002) Maternal vitamin use and reduced risk of neuroblastoma. Epidemiology 13:575–580
Otsuka S, Maegawa S, Takamura A, Kamitani H, Watanabe T, Oshimura M, Nanba E (2009) Aberrant promoter methylation and expression of the imprinted PEG3 gene in glioma. Proc Jpn Acad Ser B Phys Biol Sci 85:157–165
Paspatis GA, Karamanolis DG (1994) Folate supplementation and adenomatous colonic polyps. Dis Colon Rectum 37:1340–1341
Pathak S, Bhatla N, Singh N (2012) Cervical cancer pathogenesis is associated with one-carbon metabolism. Mol Cell Biochem 369:1–7
Pelengaris S, Khan M, Evan G (2002) c-MYC: more than just a matter of life and death. Nat Rev Cancer 2:764–776
Pelucchi C, Galeone C, Talamini R, Negri E, Parpinel M, Franceschi S, Montella M, La Vecchia C (2005a) Dietary folate and risk of prostate cancer in Italy. Cancer Epidemiol Biomarkers Prev 14:944–948
Pelucchi C, Mereghetti M, Talamini R, Negri E, Montella M, Ramazzotti V, Franceschi S, La Vecchia C (2005b) Dietary folate, alcohol consumption, and risk of ovarian cancer in an Italian case-control study. Cancer Epidemiol Biomarkers Prev 14:2056–2058
Persson EC, Schwartz LM, Park Y, Trabert B, Hollenbeck AR, Graubard BI, Freedman ND, McGlynn KA (2013) Alcohol consumption, folate intake, hepatocellular carcinoma, and liver disease mortality. Cancer Epidemiol Biomarkers Prev 22:415–421
Piyathilake CJ, Macaluso M, Brill I, Heimburger DC, Partridge EE (2007) Lower red blood cell folate enhances the HPV-16-associated risk of cervical intraepithelial neoplasia. Nutrition 23:203–210
Piyathilake CJ, Macaluso M, Alvarez RD, Bell WC, Heimburger DC, Partridge EE (2009) Lower risk of cervical intraepithelial neoplasia in women with high plasma folate and sufficient vitamin B12 in the post-folic acid fortification era. Cancer Prev Res 2:658–664
Piyathilake CJ, Macaluso M, Alvarez RD, Chen M, Badiga S, Siddiqui NR, Edberg JC, Partridge EE, Johanning GL (2011) A higher degree of LINE-1 methylation in peripheral blood mononuclear cells, a one-carbon nutrient related epigenetic alteration, is associated with a lower risk of developing cervical intraepithelial neoplasia. Nutrition 27:513–519
Pogribny IP, Ross SA, Wise C, Pogribna M, Jones EA, Tryndyak VP, James SJ, Dragan YP, Poirier LA (2006) Irreversible global DNA hypomethylation as a key step in hepatocarcinogenesis induced by dietary methyl deficiency. Mutat Res 593:80–87
Pogribny IP, Tryndyak VP, Muskhelishvili L, Rusyn I, Ross SA (2007) Methyl deficiency, alterations in global histone modifications, and carcinogenesis. J Nutr 137:216S–222S
Pogribny IP, Karpf AR, James SR, Melnyk S, Han T, Tryndyak VP (2008) Epigenetic alterations in the brains of Fisher 344 rats induced by long-term administration of folate/methyl-deficient diet. Brain Res 1237:25–34
Pogribny IP, Shpyleva SI, Muskhelishvili L, Bagnyukova TV, James SJ, Beland FA (2009a) Role of DNA damage and alterations in cytosine DNA methylation in rat liver carcinogenesis induced by a methyl-deficient diet. Mutat Res 669:56–62
Pogribny IP, Tryndyak VP, Bagnyukova TV, Melnyk S, Montgomery B, Ross SA, Latendresse JR, Rusyn I, Beland FA (2009b) Hepatic epigenetic phenotype predetermines individual susceptibility to hepatic steatosis in mice fed a lipogenic methyl-deficient diet. J Hepatol 51:176–186
Potter JD (2002) Methyl supply, methyl metabolizing enzymes and colorectal neoplasia. J Nutr 132:2410S–2412S
Pufulete M, Al-Ghnaniem R, Leather AJ, Appleby P, Gout S, Terry C, Emery PW, Sanders TA (2003) Folate status, genomic DNA hypomethylation, and risk of colorectal adenoma and cancer: a case control study. Gastroenterology 124:1240–1248
Pufulete M, Al-Ghnaniem R, Khushal A, Appleby P, Harris N, Gout S, Emery PW, Sanders TA (2005a) Effect of folic acid supplementation on genomic DNA methylation in patients with colorectal adenoma. Gut 54:648–653
Pufulete M, Al-Ghnaniem R, Rennie JA, Appleby P, Harris N, Gout S, Emery PW, Sanders TA (2005b) Influence of folate status on genomic DNA methylation in colonic mucosa of subjects without colorectal adenoma or cancer. Br J Cancer 92:838–842
Qin X, Peng Q, Chen Z, Deng Y, Huang S, Xu J, Li H, Li S, Zhao J (2013) The association between MTHFR gene polymorphisms and hepatocellular carcinoma risk: a meta-analysis. PLoS One 8:e56070
Quinlivan EP, Gregory JF 3rd (2003) The impact of food fortification on folic acid intake in Canada. Can J Public Health 94:154
Ragasudha PN, Thulaseedharan JV, Wesley R, Jayaprakash PG, Lalitha P, Pillai MR (2012) A case-control nutrigenomic study on the synergistic activity of folate and vitamin B12 in cervical cancer progression. Nutr Cancer 64:550–558
Rampersaud GC, Kauwell GP, Hutson AD, Cerda JJ, Bailey LB (2000) Genomic DNA methylation decreases in response to moderate folate depletion in elderly women. Am J Clin Nutr 72:998–1003
Ray JG, Goodman J, O’Mahoney PRA, Mamdani MM, Jiang D (2008) High rate of maternal vitamin B12 deficiency nearly a decade after Canadian folic acid flour fortification. QJM 101:475–477
Razzak AA, Oxentenko AS, Vierkant RA, Tillmans LS, Wang AH, Weisenberger DJ, Laird PW, Lynch CF, Anderson KE, French AJ, Haile RW, Harnack LJ, Potter JD, Slager SL, Smyrk TC, Thibodeau SN, Cerhan JR, Limburg PJ (2012) Associations between intake of folate and related micronutrients with molecularly defined colorectal cancer risks in the Iowa Women’s Health Study. Nutr Cancer 64:899–910
Richman EL, Kenfield SA, Stampfer MJ, Giovannucci EL, Zeisel SH, Willett WC, Chan JM (2012) Choline intake and risk of lethal prostate cancer: incidence and survival. Am J Clin Nutr 96:855–863
Robertson KD, Wolffe AP (2000) DNA methylation in health and disease. Nat Rev Genet 1:11–19
Robien K (2005) Folate during antifolate chemotherapy: what we know… and do not know. Nutr Clin Pract 20:411–422
Roddam A, Allen N, Appleby P, Key T (2008) Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. J Natl Cancer Inst 100:170–183
Rong N, Selhub J, Goldin BR, Rosenberg IH (1991) Bacterially synthesized folate in rat large-intestine is incorporated into host tissue folyl polyglutamates. J Nutr 121:1955–1959
Ropero S, Esteller M (2007) The role of histone deacetylases (HDACs) in human cancer. Mol Oncol 1:19–25
Rosenfeld CS (2010) Animal models to study environmental epigenetics. Biol Reprod 82:473–488
Ross JA, Blair CK, Olshan AF, Robison LL, Smith FO, Heerema NA, Roesler M (2005) Periconceptional vitamin use and leukemia risk in children with Down syndrome: a Children’s Oncology Group study. Cancer 104:405–410
Ryan-Harshman M, Aldoori W (2008) Vitamin B12 and health. Can Fam Physician 54:536–541
Saavedra KP, Brebi PM, Roa JC (2012) Epigenetic alterations in preneoplastic and neoplastic lesions of the cervix. Clin Epigenetics 4:13
Salazar-Martinez E, Lazcano-Ponce EC, Lira-Lira GG, Escudero-De Los Rios P, Hernandez-Avila M (2002) Nutritional determinants of epithelial ovarian cancer risk: a case-control study in Mexico. Oncology 63:151–157
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 E, Wolpin B, Rifai N, Cochrane B, Manson JA, Ma J, Giovannucci E, Thomson C, Stampfer MJ, Fuchs C (2007) Plasma folate, vitamin B6, vitamin B12, and homocysteine and pancreatic cancer risk in four large cohorts. Cancer Res 67:5553–5560
Schernhammer ES, Giovannucci E, Kawasaki T, Rosner B, Fuchs C, Ogino S (2009) Dietary folate, alcohol, and B vitamins in relation to LINE-1 hypomethylation in colon cancer. Gut 59(6):794–799
Schuz J, Weihkopf T, Kaatsch P (2007) Medication use during pregnancy and the risk of childhood cancer in the offspring. Eur J Pediatr 166:433–441
Seeber LM, Van Diest PJ (2012) Epigenetics in ovarian cancer. Methods Mol Biol 863:253–269
Shabbeer S, Williams SA, Simons BW, Herman JG, Carducci MA (2012) Progression of prostate carcinogenesis and dietary methyl donors: temporal dependence. Cancer Prev Res (Phila) 5:229–239
Shakur YA, Garriguet D, Corey P, O’Connor DL (2010) Folic acid fortification above mandated levels results in a low prevalence of folate inadequacy among Canadians. Am J Clin Nutr 92:818–825
Shane B (1995) Folate chemistry and metabolism. In: Bailey LB (ed) Folate in health and disease. Marcel Dekker, New York
Shannon J, Phoutrides E, Palma A, Farris P, Peters L, Forester A, Tillotson CJ, Garzotto M (2009) Folate intake and prostate cancer risk: a case-control study. Nutr Cancer 61:617–628
Shaw GM, Carmichael SL, Yang W, Selvin S, Schaffer DM (2004) Periconceptional dietary intake of choline and betaine and neural tube defects in offspring. Am J Epidemiol 160:102–109
Shaw GM, Finnell RH, Blom HJ, Carmichael SL, Vollset SE, Yang W, Ueland PM (2009) Choline and risk of neural tube defects in a folate-fortified population. Epidemiology 20:714–719
Shelnutt KP, Kauwell GP, Gregory JF 3rd, Maneval DR, Quinlivan EP, Theriaque DW, Henderson GN, Bailey LB (2004) Methylenetetrahydrofolate reductase 677C → T polymorphism affects DNA methylation in response to controlled folate intake in young women. J Nutr Biochem 15:554–560
Shimizu K, Onishi M, Sugata E, Sokuza Y, Mori C, Nishikawa T, Honoki K, Tsujiuchi T (2007) Disturbance of DNA methylation patterns in the early phase of hepatocarcinogenesis induced by a choline-deficient L-amino acid-defined diet in rats. Cancer Sci 98:1318–1322
Shrubsole MJ, Jin F, Dai Q, Shu XO, Potter JD, Hebert JR, Gao YT, Zheng W (2001) Dietary folate intake and breast cancer risk: results from the Shanghai Breast Cancer Study. Cancer Res 61:7136–7141
Shrubsole MJ, Shu XO, Li HL, Cai H, Yang G, Gao YT, Gao J, Zheng W (2011) Dietary B vitamin and methionine intakes and breast cancer risk among Chinese women. Am J Epidemiol 173:1171–1182
Shuangshoti S, Hourpai N, Pulmsuk U, Mutirangura A (2007) Line-1 hypomethylation in multistage carcinogenesis of the uterine cervix. Asian Pac J Cancer Prev 8:307–309
Sie KKY, Chen JM, Sohn KJ, Croxford R, Thompson LU, Kim YI (2009) Folic acid supplementation provided in utero and during lactation reduces the number of terminal end buds of the developing mammary glands in the offspring. Cancer Lett 280:72–77
Sie KK, Medline A, Van Weel J, Sohn KJ, Choi SW, Croxford R, Kim YI (2011) Effect of maternal and postweaning folic acid supplementation on colorectal cancer risk in the offspring. Gut 60(12):1687–1694
Sie KK, Li J, Ly A, Sohn KJ, Croxford R, Kim YI (2013) Effect of maternal and postweaning folic acid supplementation on global and gene-specific DNA methylation in the liver of the rat offspring. Mol Nutr Food Res 57(4):677–685
Silvera SAN, Jain M, Howe GR, Miller AB, Rohan TE (2006) Dietary folate consumption and risk of ovarian cancer: a prospective cohort study. Eur J Cancer Prev 15:511–515
Sinclair KD, Allegrucci C, Singh R, Gardner DS, Sebastian S, Bispham J, Thurston A, Huntley JF, Rees WD, Maloney CA, Lea RG, Craigon J, McEvoy TG, Young LE (2007) DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status. Proc Natl Acad Sci U S A 104:19351–19356
Skinner HG, Michaud DS, Giovannucci EL, Rimm EB, Stampfer MJ, Willett WC, Colditz GA, Fuchs CS (2004) A prospective study of folate intake and the risk of pancreatic cancer in men and women. Am J Epidemiol 160:248–258
Slattery ML, Curtin K, Sweeny C, Levin TR, Potter JD, Wolff RK, Albertsen H, Samowitz WS (2006) Diet and lifestyle factor associations with CpG island methylator phenotype and BRAF mutations in colon cancer. Int J Cancer 120:656–663
Smith AD, Kim YI, Refsum H (2008) Is folic acid good for everyone? Am J Clin Nutr 87:517–533
Sohn KJ, Stempak JM, Reid S, Shirwadkar S, Mason JB, Kim YI (2003) The effect of dietary folate on genomic and p53-specific DNA methylation in rat colon. Carcinogenesis 24:81–90
Song YQ, Manson JE, Lee IM, Cook NR, Paul L, Selhub J, Giovannucci E, Zhang SMM (2012) Effect of combined folic acid, vitamin B-6, and vitamin B-12 on colorectal adenoma. J Natl Cancer Inst 104:1562–1575
Song MA, Tiirikainen M, Kwee S, Okimoto G, Yu H, Wong LL (2013) Elucidating the landscape of aberrant DNA methylation in hepatocellular carcinoma. PLoS One 8:e55761
Steegers-Theunissen RP, Obermann-Borst SA, Kremer D, Lindemans J, Siebel C, Steegers EA, Slagboom PE, Heijmans BT (2009) Periconceptional maternal folic acid use of 400 microg per day is related to increased methylation of the IGF2 gene in the very young child. PLoS One 4:e7845
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
Stevens VL, Rodriguez C, Pavluck AL, McCullough ML, Thun MJ, Calle EE (2006) Folate nutrition and prostate cancer incidence in a large cohort of US men. Am J Epidemiol 163:989–996
Stevens VL, McCullough ML, Sun JZ, Gapstur SM (2010) Folate and other one-carbon metabolism-related nutrients and risk of postmenopausal breast cancer in the Cancer Prevention Study II Nutrition Cohort. Am J Clin Nutr 91:1708–1715
Stevens VL, McCullough ML, Sun J, Jacobs EJ, Campbell PT, Gapstur SM (2011) High levels of folate from supplements and fortification are not associated with increased risk of colorectal cancer. Gastroenterology 141:98–105, 105.e1
Stolzenberg-Solomon RZ, Albanes D, Nieto FJ, Hartman TJ, Tangrea JA, Rautalahti M, Sehlub J, Virtamo J, Taylor PR (1999) Pancreatic cancer risk and nutrition-related methyl-group availability indicators in male smokers. J Natl Cancer Inst 91:535–541
Stolzenberg-Solomon RZ, Pietinen P, Barrett MJ, Taylor PR, Virtamo J, Albanes D (2001) Dietary and other methyl-group availability factors and pancreatic cancer risk in a cohort of male smokers. Am J Epidemiol 153:680–687
Tajima S, Suetake I (1998) Regulation and function of DNA methylation in vertebrates. J Biochem 123:993–999
Tao MH, Freudenheim JL (2010) DNA methylation in endometrial cancer. Epigenetics 5:491–498
Tao MH, Mason JB, Marian C, McCann SE, Platek ME, Millen A, Ambrosone C, Edge SB, Krishnan SS, Trevisan M, Shields PG, Freudenheim JL (2011) Promoter methylation of E-Cadherin, p16, and RAR-beta(2) genes in breast tumors and dietary intake of nutrients important in one-carbon metabolism. Nutr Cancer 63:1143–1150
Teegarden D, Romieu I, Lelievre SA (2012) Redefining the impact of nutrition on breast cancer incidence: is epigenetics involved? Nutr Res Rev 25:68–95
Thompson JR, Gerald PF, Willoughby ML, Armstrong BK (2001) Maternal folate supplementation in pregnancy and protection against acute lymphoblastic leukaemia in childhood: a case-control study. Lancet 358:1935–1940
Tong SY, Kim MK, Lee JK, Lee JM, Choi SW, Friso S, Song ES, Lee KB, Lee JP (2011) Common polymorphisms in methylenetetrahydrofolate reductase gene are associated with risks of cervical intraepithelial neoplasia and cervical cancer in women with low serum folate and vitamin B12. Cancer Causes Control 22:63–72
Toole JF, Malinow MR, Chambless LE, Spence JD, Pettigrew LC, Howard VJ, Sides EG, Wang CH, Stampfer M (2004) Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA 291:565–575
Toyota M, Ahuja N, Ohe-Toyota M, Herman JG, Baylin SB, Issa JP (1999) CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci U S A 96:8681–8686
Tsang V, Fry RC, Niculescu MD, Rager JE, Saunders J, Paul DS, Zeisel SH, Waalkes MP, Styblo M, Drobna Z (2012) The epigenetic effects of a high prenatal folate intake in male mouse fetuses exposed in utero to arsenic. Toxicol Appl Pharmacol 264:439–450
Tworoger SS, Hecht JL, Giovannucci E, Hankinson SE (2006) Intake of folate and related nutrients in relation to risk of epithelial ovarian cancer. Am J Epidemiol 163:1101–1111
Uccella S, Cha SS, Melton LJ 3rd, Bergstralh EJ, Boardman LA, Keeney GL, Podratz KC, Ciancio FF, Mariani A (2011a) Risk factors for developing multiple malignancies in patients with endometrial cancer. Int J Gynecol Cancer 21:896–901
Uccella S, Mariani A, Wang AH, Vierkant RA, Robien K, Anderson KE, Cerhan JR (2011b) Dietary and supplemental intake of one-carbon nutrients and the risk of type I and type II endometrial cancer: a prospective cohort study. Ann Oncol 22:2129–2136
Ueland PM (2011) Choline and betaine in health and disease. J Inherit Metab Dis 34:3–15
Ulrich CM, Toriola AT, Koepl LM, Sandifer T, Poole EM, Duggan C, McTiernan A, Issa JP (2012) Metabolic, hormonal and immunological associations with global DNA methylation among postmenopausal women. Epigenetics 7:1020–1028
Van Den Donk M, Pellis L, Crott JW, Van Engeland M, Friederich P, Nagengast FM, Van Bergeijk JD, De Boer SY, Mason JB, Kok FJ, Keijer J, Kampman E (2007a) Folic acid and vitamin B-12 supplementation does not favorably influence uracil incorporation and promoter methylation in rectal mucosa DNA of subjects with previous colorectal adenomas. J Nutr 137:2114–2120
Van Den Donk M, Van Engeland M, Pellis L, Witteman BJ, Kok FJ, Keijer J, Kampman E (2007b) Dietary folate intake in combination with MTHFR C677T genotype and promoter methylation of tumor suppressor and DNA repair genes in sporadic colorectal adenomas. Cancer Epidemiol Biomarkers Prev 16:327–333
Van Engeland M, Weijenberg MP, Roemen GM, Brink M, De Bruine AP, Goldbohm RA, Van Den Brandt PA, Baylin SB, De Goeij AF, Herman JG (2003) Effects of dietary folate and alcohol intake on promoter methylation in sporadic colorectal cancer: the Netherlands cohort study on diet and cancer. Cancer Res 63:3133–3137
Van Guelpen B, Dahlin AM, Hultdin J, Eklof V, Johansson I, Henriksson ML, Cullman I, Hallmans G, Palmqvist R (2010) One-carbon metabolism and CpG island methylator phenotype status in incident colorectal cancer: a nested case-referent study. Cancer Causes Control 21:557–566
Van Wijk N, Watkins CJ, Bohlke M, Maher TJ, Hageman RJJ, Kamphuis P, Broersen LM, Wurtman RJ (2012) Plasma choline concentration varies with different dietary levels of vitamins B-6, B-12 and folic acid in rats maintained on choline-adequate diets. Br J Nutr 107:1408–1412
Vargas AJ, Thompson PA (2012) Diet and nutrient factors in colorectal cancer risk. Nutr Clin Pract 27:613–623
Velicer CM, Ulrich CM (2008) Vitamin and mineral supplement use among US adults after cancer diagnosis: a systematic review. J Clin Oncol 26:665–673
Verhage BAJ, Cremers P, Schouten LJ, Goldbohm RA, Van Den Brandt PA (2012) Dietary folate and folate vitamers and the risk of prostate cancer in The Netherlands Cohort Study. Cancer Causes Control 23:2003–2011
Vlajinac HD, Marinkovic JM, Ilic MD, Kocev NI (1997) Diet and prostate cancer: a case-control study. Eur J Cancer 33:101–107
Vollset SE, Igland J, Jenab M, Fredriksen A, Meyer K, Eussen S, Gjessing HK, Ueland PM, Pera G, Sala N, Agudo A, Capella G, Del Giudice G, Palli D, Boeing H, Weikert C, Bueno-De-Mesquita HB, Carneiro F, Pala V, Vineis P, Tumino R, Panico S, Berglund G, Manjer J, Stenling R, Hallmans G, Martinez C, Dorronsoro M, Barricarte A, Navarro C, Quiros JR, Allen N, Key TJ, Bingham S, Linseisen J, Kaaks R, Overvad K, Tjonneland A, Buchner FL, Peeters PHM, Numans ME, Clavel-Chapelon F, Boutron-Ruault M-C, Trichopoulou A, Lund E, Slimani N, Ferrari P, Riboli E, Gonzalez CA (2007) The association of gastric cancer risk with plasma folate, cobalamin, and Methylenetetrahydrofolate reductase polymorphisms in the European prospective investigation into cancer and nutrition. Cancer Epidemiol Biomarkers Prev 16:2416–2424
Vollset SE, Clarke R, Lewington S, Ebbing M, Halsey J, Lonn E, Armitage J, Manson JE, Hankey GJ, Spence JD, Galan P, Bonaa KH, Jamison R, Gaziano JM, Guarino P, Baron JA, Logan RF, Giovannucci EL, Den Heijer M, Ueland PM, Bennett D, Collins R, Peto R (2013) Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50 000 individuals. Lancet 381(9871):1029–1036
Wainfan E, Poirier LA (1992) Methyl-groups in carcinogenesis—effects on DNA methylation and gene-expression. Cancer Res 52:S2071–S2077
Wainfan E, Dizik M, Stender M, Christman JK (1989) Rapid appearance of hypomethylated DNA in livers of rats fed cancer-promoting, methyl-deficient diets. Cancer Res 49:4094–4097
Wallace K, Grau MV, Levine AJ, Shen L, Hamdan R, Chen X, Gui J, Haile RW, Barry EL, Ahnen D, McKeown-Eyssen G, Baron JA, Issa JP (2010) Association between folate levels and CpG Island hypermethylation in normal colorectal mucosa. Cancer Prev Res (Phila) 3:1552–1564
Wang J, Sasco AJ, Fu C, Xue H, Guo G, Hua Z, Zhou Q, Jiang Q, Xu B (2008) Aberrant DNA methylation of P16, MGMT, and hMLH1 genes in combination with MTHFR C677T genetic polymorphism in esophageal squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev 17:118–125
Wasson GR, McGlynn AP, McNulty H, O’Reilly SL, McKelvey-Martin VJ, McKerr G, Strain JJ, Scott J, Downes CS (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
Watanabe F (2007) Vitamin B12 sources and bioavailability. Exp Biol Med 232:1266–1274
Waterland RA, Jirtle RL (2003) Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol 23:5293–5300
Waterland RA, Dolinoy DC, Lin JR, Smith CA, Shi X, Tahiliani KG (2006a) Maternal methyl supplements increase offspring DNA methylation at Axin Fused. Genesis 44:401–406
Waterland RA, Lin JR, Smith CA, Jirtle RL (2006b) Post-weaning diet affects genomic imprinting at the insulin-like growth factor 2 (Igf2) locus. Hum Mol Genet 15:705–716
Waterland RA, Travisano M, Tahiliani KG (2007) Diet-induced hypermethylation at agouti viable yellow is not inherited transgenerationally through the female. FASEB J 21:3380–3385
Webb PM, Ibiebele TI, Hughes MC, Beesley J, Van Der Pols JC, Chen X, Nagle CM, Bain CJ, Chenevix-Trench G, Australian Cancer Study (Ovarian Cancer), Australian Ovarian Cancer Study Group (2011) Folate and related micronutrients, folate-metabolising genes and risk of ovarian cancer. Eur J Clin Nutr 65:1133–1140
Weinstein SJ, Hartman TJ, Stolzenberg-Solomon R, Pietinen P, Barrett MJ, Taylor PR, Virtamo J, Albanes D (2003) Null association between prostate cancer and serum folate, vitamin B(6), vitamin B(12), and homocysteine. Cancer Epidemiol Biomarkers Prev 12:1271–1272
Weinstein SJ, Stolzenberg-Solomon R, Pietinen P, Taylor PR, Virtamo J, Albanes D (2006) Dietary factors of one-carbon metabolism and prostate cancer risk. Am J Clin Nutr 84:929–935
Weinstein SJ, Albanes D, Selhub J, Graubard B, Lim U, Taylor PR, Virtamo J, Stolzenberg-Solomon R (2008) One-carbon metabolism biomarkers and risk of colon and rectal cancers. Cancer Epidemiol Biomarkers Prev 17:3233–3240
Welzel TM, Katki HA, Sakoda LC, Evans AA, London WT, Chen G, O’Broin S, Shen FM, Lin WY, McGlynn KA (2007) Blood folate levels and risk of liver damage and hepatocellular carcinoma in a prospective high-risk cohort. Cancer Epidemiol Biomarkers Prev 16:1279–1282
Wen W, Shu XO, Potter JD, Severson RK, Buckley JD, Reaman GH, Robison LL (2002) Parental medication use and risk of childhood acute lymphoblastic leukemia. Cancer 95:1786–1794
Weng Y-R, Sun D-F, Fang J-Y, Gu W-Q, Zhu H-Y (2006) Folate levels in mucosal tissue but not methylenetetrahydrofolate reductase polymorphisms are associated with gastric carcinogenesis. World J Gastroenterol 12:7591–7597
Westgren M (2012) Prevention of ovarian cancer—let’s do something. Acta Obstet Gynecol Scand 91:1009–1010
Wien TN, Pike E, Wisløff T, Staff A, Smeland S, Klemp M (2012) Cancer risk with folic acid supplements: a systematic review and meta-analysis. BMJ Open 2
Williams CD, Satia JA, Adair LS, Stevens J, Galanko J, Keku TO, Sandler RS (2010) Antioxidant and DNA methylation-related nutrients and risk of distal colorectal cancer. Cancer Causes Control 21:1171–1181
Wilson MJ, Shivapurkar N, Poirier LA (1984) Hypomethylation of hepatic nuclear-DNA in rats fed with a carcinogenic methyl-deficient diet. Biochem J 218:987–990
Wilson RD, Johnson JA, Wyatt P, Allen V, Gagnon A, Langlois S, Blight C, Audibert F, Desilets V, Brock JA, Koren G, Goh YI, Nguyen P, Kapur B (2007) Pre-conceptional vitamin/folic acid supplementation 2007: the use of folic acid in combination with a multivitamin supplement for the prevention of neural tube defects and other congenital anomalies. J Obstet Gynaecol Can 29:1003–1026
Wolff GL, Roberts DW, Morrissey RL, Greenman DL, Allen RR, Campbell WL, Bergman H, Nesnow S, Frith CH (1987) Tumorigenic responses to lindane in mice—potentiation by a dominant mutation. Carcinogenesis 8:1889–1897
Wolff GL, Kodell RL, Moore SR, Cooney CA (1998) Maternal epigenetics and methyl supplements affect agouti gene expression in Avy/a mice. FASEB J 12:949–957
Wu KN, Helzlsouer KJ, Comstock GW, Hoffman SC, Nadeau MR, Selhub J (1999) A prospective study on folate, B12, and pyridoxal 5′-phosphate (B6) and breast cancer. Cancer Epidemiol Biomarkers Prev 8:209–217
Xiang TX, Yuan Y, Li LL, Wang ZH, Dan LY, Chen Y, Ren GS, Tao Q (2013) Aberrant promoter CpG methylation and its translational applications in breast cancer. Chin J Cancer 32:12–20
Xiao SD, Meng XJ, Shi Y, Hu YB, Zhu SS, Wang CW (2002) Interventional study of high dose folic acid in gastric carcinogenesis in beagles. Gut 50:61–64
Xu XR, Chen J (2009) One-carbon metabolism and breast cancer: an epidemiological perspective. J Genet Genomics 36:203–214
Xu WH, Shrubsole MJ, Xiang YB, Cai QY, Zhao GM, Ruan ZX, Cheng JR, Zheng W, Shu XO (2007) Dietary folate intake, MTHFR genetic polymorphisms, and the risk of endometrial cancer among Chinese women. Cancer Epidemiol Biomarkers Prev 16:281–287
Xu XR, Gammon MD, Zeisel SH, Bradshaw PT, Wetmur JG, Teitelbaum SL, Neugut AI, Santella RM, Chen J (2009a) High intakes of choline and betaine reduce breast cancer mortality in a population-based study. FASEB J 23:4022–4028
Xu XR, Gammon MD, Zhang YJ, Bestor TH, Zeisel SH, Wetmur JG, Wallenstein S, Bradshaw PT, Garbowski G, Teitelbaum SL, Neugut AI, Santella RM, Chen J (2009b) BRCA1 promoter methylation is associated with increased mortality among women with breast cancer. Breast Cancer Res Treat 115:397–404
Xu X, Gammon MD, Jefferson E, Zhang Y, Cho YH, Wetmur JG, Teitelbaum SL, Bradshaw PT, Terry MB, Garbowski G, Hibshoosh H, Neugut AI, Santella RM, Chen J (2011) The influence of one-carbon metabolism on gene promoter methylation in a population-based breast cancer study. Epigenetics 6:1276–1283
Xu XR, Gammon MD, Hernandez-Vargas H, Herceg Z, Wetmur JG, Teitelbaum SL, Bradshaw PT, Neugut AI, Santella RM, Chen J (2012) DNA methylation in peripheral blood measured by LUMA is associated with breast cancer in a population-based study. FASEB J 26:2657–2666
Yang K, Kurihara N, Fan K, Newmark H, Rigas B, Bancroft L, Corner G, Livote E, Lesser M, Edelmann W, Velcich A, Lipkin M, Augenlicht L (2008) Dietary induction of colonic tumors in a mouse model of sporadic colon cancer. Cancer Res 68:7803–7810
Yen TT, Gill AM, Frigeri LG, Barsh GS, Wolff GL (1994) Obesity, diabetes, and neoplasia in yellow A(vy)/-mice—ectopic expression of the agouti gene. FASEB J 8:479–488
Yetley EA, Coates PM, Johnson CL (2011a) Overview of a roundtable on NHANES monitoring of biomarkers of folate and vitamin B-12 status: measurement procedure issues. Am J Clin Nutr 94:297S–302S
Yetley EA, Pfeiffer CM, Phinney KW, Bailey RL, Blackmore S, Bock JL, Brody LC, Carmel R, Curtin LR, Durazo-Arvizu R, Eckfeldt JH, Green R, Gregory JF, Hoofnagle AN, Jacobsen DW, Jacques PF, Lacher DA, Molloy AM, Massaro J, Mills JL, Nexo E, Rader JI, Selhub J, Sempos C, Shane B, Stabler S, Stover P, Tamura T, Tedstone A, Thorpe SJ, Coates PM, Johnson CL, Picciano MF (2011b) Biomarkers of vitamin B-12 status in NHANES: a roundtable summary. Am J Clin Nutr 94:313S–321S
Yeung L, Yang QH, Berry RJ (2008) Contributions of Total Daily Intake of Folic Acid to Serum Folate Concentrations. JAMA 300:2486–2487
Ying J, Rahbar MH, Hallman DM, Hernandez LM, Spitz MR, Forman MR, Gorlova OY (2013) Associations between dietary intake of choline and betaine and lung cancer risk. PLoS One 8
Zeisel SH (2005) Choline, homocysteine, and pregnancy. Am J Clin Nutr 82:719–720
Zeisel SH, Da Costa KA (2009) Choline: an essential nutrient for public health. Nutr Rev 67:615–623
Zhang SM, Willett WC, Selhub J, Hunter DJ, Giovannucci EL, Holmes MD, Colditz GA, Hankinson SE (2003) Plasma folate, vitamin B6, vitamin B12, homocysteine, and risk of breast cancer. J Natl Cancer Inst 95:373–380
Zhang C-X, Ho SC, Chen Y-M, Lin F-Y, Fu J-H, Cheng S-Z (2011) Dietary folate, vitamin B6, vitamin B12 and methionine intake and the risk of breast cancer by oestrogen and progesterone receptor status. Br J Nutr 106:936–943
Zhang CX, Pan MX, Li B, Wang L, Mo XF, Chen YM, Lin FY, Ho SC (2013a) Choline and betaine intake is inversely associated with breast cancer risk: a two-stage case-control study in China. Cancer Sci 104:250–258
Zhang X-H, Ma J, Smith-Warner SA, Lee JE, Giovannucci E (2013b) Vitamin B6 and colorectal cancer: current evidence and future directions. World J Gastroenterol 19:1005
Zhao H, Li Q, Wang J, Su X, Ng KM, Qiu T, Shan L, Ling Y, Wang L, Cai J, Ying J (2012) Frequent epigenetic silencing of the folate-metabolising gene cystathionine-beta-synthase in gastrointestinal cancer. PLoS One 7
Ziegler RG, Jones CJ, Brinton LA, Norman SA, Mallin K, Levine RS, Lehman HF, Hamman RF, Trumble AC, Rosenthal JF et al (1991) Diet and the risk of in situ cervical cancer among white women in the United States. Cancer Causes Control 2:17–29
Zschabitz S, Cheng TYD, Neuhouser ML, Zheng YY, Ray RM, Miller JW, Song XL, Maneval DR, Beresford SAA, Lane D, Shikany JM, Ulrich CM (2013) B vitamin intakes and incidence of colorectal cancer: results from the Women’s Health Initiative Observational Study cohort. Am J Clin Nutr 97:332–343
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer Science+Business Media New York
About this chapter
Cite this chapter
Masih, S., Plumptre, L.A., Kim, YI. (2014). One-Carbon Metabolism Nutrients and Epigenetics: A Mechanistic Link Between Aberrant One-Carbon Metabolism and Cancer Risk?. In: Maulik, N., Karagiannis, T. (eds) Molecular mechanisms and physiology of disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0706-9_11
Download citation
DOI: https://doi.org/10.1007/978-1-4939-0706-9_11
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4939-0705-2
Online ISBN: 978-1-4939-0706-9
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)