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Epigenetic Perturbations in the Context of the Multi-hit Hypothesis of Carcinogenesis

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Molecular mechanisms and physiology of disease

Abstract

Since 1950, a large number of models tried to represent the tumorigenesis process; numerous theories have overlapped and have been changed or improved along the way. Recently the significant role of epigenetics has emerged. These dynamic modifications are strongly linked to genetic and environmental factors and are involved in cancer development. The chapter highlights the contribution of the epigenetics in the multi-hit process of carcinogenesis, focusing on tumors with the highest incidence and mortality. Moreover the complex interplay between genetics and epigenetics will be discussed, such as the link between DNMT mutations and aberrant promoter methylation in several critical genes. Lifestyle factors such as smoking, alcohol and fat consumption, and stress have definitely an important role in carcinogenesis, and may act through epigenetic mechanisms. However numerous questions remain still unresolved, and continuous experimental researches are required.

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References

  • Ai L, Kim WJ, Kim TY, Fields CR, Massoll NA, Robertson KD, Brown KD (2006) Epigenetic silencing of the tumor suppressor cystatin M occurs during breast cancer progression. Cancer Res 66:7899–7909

    Article  CAS  PubMed  Google Scholar 

  • Albany C, Alva AS, Aparicio AM, Singal R, Yellapragada S, Sonpavde G, Hahn NM (2011) Epigenetics in prostate cancer. Prostate Cancer 2011:580318

    Article  PubMed Central  PubMed  Google Scholar 

  • Alfred G, Knudson JR (1971) Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A 68:820–823

    Article  Google Scholar 

  • Alvarez H, Opalinska J, Zhou L, Sohal D, Fazzari MJ, Yu Y, Montagna C, Montgomery EA, Canto M, Dunbar KB, Wang J, Roa JC, Mo Y, 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:e1001356

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Arasaradnam RP, Commane DM, Bradburn D, Mathers JC (2008) A review of dietary factors and its influence on DNA methylation in colorectal carcinogenesis. Epigenetics 3:193–198

    Article  CAS  PubMed  Google Scholar 

  • Arita A, Niu J, Qu Q, Zhao N, Ruan Y, Nadas A, Chervona Y, Wu F, Sun H, Hayes RB, Costa M (2011) Global levels of histone modifications in peripheral blood mononuclear cells of subjects with exposure to nickel. Environ Health Perspect 120:198–203

    Article  PubMed Central  PubMed  Google Scholar 

  • Armitage P, Doll R (1954) The age distribution of cancer and a multi-stage theory of carcinogenesis. Br J Cancer 8:1–12

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Barretina J, Caponigro G, Stransky N, Venkatesan K, Margolina A, Kim S, Wilson CJ, Leha RJ, Kryukov GV, Sonkin D et al (2012) The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature 483:603–607

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Baylin SB, Jones PA (2011) A decade of exploring the cancer epigenome—biological and translational implications. Nat Rev Cancer 11:726–734

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Beetstra S, Thomas P, Salisbury C, Turner J, Fenech M (2005) Folic acid deficiency increases chromosomal instability, chromosome 21 aneuploidy and sensitivity to radiation-induced micronuclei. Mutat Res 578:317–326

    Article  CAS  PubMed  Google Scholar 

  • Behbahani TE, Kahl P, von der Gathen J, Heukamp LC, Baumann C, Gütgemann I, Walter B, Hofstädter F, Bastian PJ, von Ruecker A, Müller SC, Rogenhofer S, Ellinger J (2012) Alterations of global histone H4K20 methylation during prostate carcinogenesis. BMC Urol 13:12–15

    Google Scholar 

  • Berdasco M, Esteller M (2013) Genetic syndromes caused by mutations in epigenetic genes. Hum Genet 132:359–383

    Article  CAS  PubMed  Google Scholar 

  • Berger AH, Knudson AG, Pandolfi PP (2011) A continuum model for tumour suppression. Nature 476:163–169

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bernard D, Pourtier-Manzanedo A, Gil J, Beach DH (2003) Myc confers androgen-independent prostate cancer cell growth. J Clin Invest 112:1724–1731

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bianco-Miotto T, Chiam K, Buchanan G, Jindal S, Day TK, Thomas M, Pickering MA, O’Loughlin MA, Ryan NK, Raymond WA, Horvath LG, Kench JG, Stricker PD, Marshall VR, Sutherland RL, Henshall SM, Gerald WL, Scher HI, Risbridger GP, Clements JA, Butler LM, Tilley WD, Horsfall DJ, Ricciardelli C, Australian Prostate Cancer Bioresource (2010) Global levels of specific histone modifications and an epigenetic gene signature predict prostate cancer progression and development. Cancer Epidemiol Biomarkers Prev 19:2611–2622

    Article  CAS  PubMed  Google Scholar 

  • Bollati V, Marinelli B, Apostoli P, Bonzini M, Nordio F, Hoxha M, Pegoraro V, Motta V, Tarantini L, Cantone L, Schwartz J, Bertazzi PA, Baccarelli A (2010) Exposure to metal-rich particulate matter modifies the expression of candidate microRNAs in peripheral blood leukocytes. Environ Health Perspect 118:763–768

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Calvanese V, Lara E, Kahn A, Fraga MF (2009) The role of epigenetics in aging and age-related diseases. Ageing Res Rev 8:268–276

    Article  CAS  PubMed  Google Scholar 

  • Catteau A, Morris JR (2002) BRCA1 methylation: a significant role in tumour development? Semin Cancer Biol 12:359–371

    Article  CAS  PubMed  Google Scholar 

  • Centelles JJ (2012) General aspects of colorectal cancer. ISRN Oncol 2012:139268. doi:10.5402/2012/139268

    PubMed Central  PubMed  Google Scholar 

  • Chen Z, Wang L, Wang Q, Li W (2010) Histone modifications and chromatin organization in prostate cancer. Epigenomics 2:551–560

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chung JH, Lee HJ, Kim BH, Cho NY, Kang GH (2011) DNA methylation profile during multistage progression of pulmonary adenocarcinomas. Virchows Arch 459:201–211

    Article  CAS  PubMed  Google Scholar 

  • Clark SJ, Harrison J, Frommer M (1995) CpNpG methylation in mammalian cells. Nat Genet 10:20–27

    Article  CAS  PubMed  Google Scholar 

  • Coppedè F (2014) Epigenetic biomarkers of colorectal cancer: focus on DNA methylation. Cancer Lett 342:238–247

    Article  PubMed  Google Scholar 

  • Cortessis VK, Thomas DC, Levine AJ, Breton CV, Mack TM, Siegmund KD, Haile RW, Laird PW (2012) Environmental epigenetics: prospects for studying epigenetic mediation of exposure-response relationships. Hum Genet 131:1565–1589

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Crider KS, Yang TP, Berry RJ, Bailey LB (2012) Folate and DNA methylation: a review of molecular mechanisms and the evidence for folate’s role. Adv Nutr 3:21–38

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Croce CM (2009) Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet 10:704–714

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Doll R, Peto R (1978) Cigarette smoking and bronchial carcinoma: dose and time relationships among regular smokers and lifelong non-smokers. J Epidemiol Community health 32:303–313

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • 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 (Phila) 3:92–100

    Article  CAS  Google Scholar 

  • Dworkin AM, Spearman AD, Tseng SY, Sweet K, Toland AE (2009) Methylation not a frequent “second hit” in tumors with germline BRCA mutations. Fam Cancer 8:339–346

    Article  CAS  PubMed  Google Scholar 

  • Esquela-Kerscher A, Slack FJ (2006) Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer 6:259–269

    Article  CAS  PubMed  Google Scholar 

  • Esteller M (2012) Cancer, epigenetics and the Nobel Prizes. Mol Oncol 6:565–566

    Article  PubMed  Google Scholar 

  • Esteller M, Silva JM, Dominguez G, Bonilla F, Matias-Guiu X, Lerma E, Bussaglia E, Prat J, Harkes C, Repasky EA et al (2000) Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors. J Natl Cancer Inst 92:564–569

    Article  CAS  PubMed  Google Scholar 

  • Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61:759–767

    Article  CAS  PubMed  Google Scholar 

  • Fraga MF, Agrelo R, Esteller M (2007) Cross-talk between aging and cancer: the epigenetic language. Ann N Y Acad Sci 1100:60–74

    Article  CAS  PubMed  Google Scholar 

  • Frey LJ, Piccolo SR, Edgerton ME (2011) Multiplicity: an organizing principle for cancers and somatic mutations. BMC Med Genomics 4:52

    Article  PubMed Central  PubMed  Google Scholar 

  • Gargalionis AN, Piperi C, Adamopoulos C, Papavassiliou AG (2012) Histone modifications as a pathogenic mechanism of colorectal tumorigenesis. Int J Biochem Cell Biol 44:1276–1289

    Article  CAS  PubMed  Google Scholar 

  • Glozak MA, Seto E (2007) Histone deacetylases and cancer. Oncogene 26:5420–5432

    Article  CAS  PubMed  Google Scholar 

  • Grady WM, Carethers JM (2008) Genomic and epigenetic instability in colorectal cancer pathogenesis. Gastroenterology 135:1079–1099

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gravina GL, Ranieri G, Muzi P, Marampon F, Mancini A, Di Pasquale B, Di Clemente L, Dolo V, D’Alessandro AM, Festuccia C (2012) Increased levels of DNA methyltransferases are associated with the tumorigenic capacity of prostate cancer cells. Oncol Rep 29:1189–1195

    PubMed  Google Scholar 

  • Hamid A, Kiran M, Rana S, KAUR J (2009) Low folate transport across intestinal basolateral surface is associated with down-regulation of reduced folate carrier in in vivo model of folate malabsorption. IUBMB Life 61:236–243

    Article  CAS  PubMed  Google Scholar 

  • Hansen KD, Timp W, Bravo HC, Sabunciyan S, Langmead B, Mcdonald OG, Wen B, Wu H, Liu Y, Diep D, Briem E, Zhang K, Irizarry RA, Feinberg AP (2011) Increased methylation variation in epigenetic domains across cancer types. Nat Genet 43:768–775

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Harquail J, Benzina S, Robichaud GA (2012) MicroRNAs and breast cancer malignancy: an overview of miRNA-regulated cancer processes leading to metastasis. Cancer Biomark 11:269–280

    CAS  PubMed  Google Scholar 

  • He X, Dong Y, Wu CW, Zhao Z, Ng SS, Chan FK, Sung JJ, Yu J (2012) MicroRNA-218 inhibits cell cycle progression and promotes apoptosis in colon cancer by downregulating oncogene BMI-1. Mol Med 18:1491–1498

    CAS  PubMed Central  Google Scholar 

  • Helenius MA, Saramäki OR, Linja MJ, Tammela TLJ, Visakorpi T (2001) Amplification of urokinase gene in prostate cancer. Cancer Res 61:5340–5344

    CAS  PubMed  Google Scholar 

  • Herceg Z, Vaissière T (2011) Epigenetic mechanisms and cancer: an interface between the environment and the genome. Epigenetics 6:804–819

    Article  CAS  PubMed  Google Scholar 

  • Hughes LA, van den Brandt PA, de Bruïne AP, Wouters KA, Hulsmans S, Spiertz A, Goldbohm RA, de Goeij AF, Herman JG, Weijenberg MP, van Engeland M (2009) Early life exposure to famine and colorectal cancer risk: a role for epigenetic mechanisms. PLoS One 4:e7951

    Article  PubMed Central  PubMed  Google Scholar 

  • Huidobro C, Fernandez AF, Fraga MF (2012) Aging epigenetics: causes and consequences. Mol Aspects Med 34:765–781

    Article  PubMed  Google Scholar 

  • Imai K, Yamamoto H (2008) Carcinogenesis and microsatellite instability: the interrelationship between genetics and epigenetics. Carcinogenesis 29:673–680

    Article  CAS  PubMed  Google Scholar 

  • Imam JS, Plyler JR, Bansal H, Prajapati S, Bansal S, Rebeles J, Chen HI, Chang YF, Panneerdoss S, Zoghi B, Buddavarapu KC, Broaddus R, Hornsby P, Tomlinson G, Dome J, Vadlamudi RK, Pertsemlidis A, Chen Y, Rao MK (2012) Genomic loss of tumor suppressor miRNA-204 promotes cancer cell migration and invasion by activating AKT/mTOR/Rac1 signaling and actin reorganization. PLoS One 7:e52397. doi:10.1371/journal.pone.0052397

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Issa JP (2008) Colon cancer: it’s CIN or CIMP. Clin Cancer Res 14:5939–5940

    Article  PubMed  Google Scholar 

  • Jardim MJ (2011) microRNAs: implications for air pollution research. Mutat Res 717:38–45

    Article  CAS  PubMed  Google Scholar 

  • Jovanovic J, Rønneberg JA, Tost J, Kristensen V (2010) The epigenetics of breast cancer. Mol Oncol 4:242–254

    Article  CAS  PubMed  Google Scholar 

  • Kanwal R, Gupta S (2012) Epigenetic modifications in cancer. Clin Genet 81:303–311

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kim YI (2005) Nutritional epigenetics: impact of folate deficiency on DNA methylation and colon cancer susceptibility. J Nutr 1:35,2703–9

    Google Scholar 

  • Kim YI (2007) Folate and colorectal cancer: an evidence-based critical review. Mol Nutr Food Res 51:267–292

    Article  CAS  PubMed  Google Scholar 

  • Kim YI (2008) Folic acid supplementation and cancer risk: point. Cancer Epidemiol Biomarkers Prev 17:2220–2225

    Article  PubMed  Google Scholar 

  • Kitkumthorn N, Mutirangura A (2011) Long interspersed nuclear element 1 hypomethylation in cancer: biology and clinical applications. Clin Epigenet 2:315–330

    Article  CAS  Google Scholar 

  • Knudson A (2005) Retinoblastoma: teacher of cancer biology and medicine. PLoS Med 2:e349

    Article  PubMed Central  PubMed  Google Scholar 

  • Lao VV, Grady WM (2011) Epigenetics and colorectal cancer. Nat Rev Gastroenterol Hepatol 8:686–700

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Leite KR, Tomiyama A, Reis ST, Sousa-Canavez JM, Sañudo A, Camara Lopes LH, Srougi M (2013) MicroRNA expression profiles in the progression of prostate cancer-from high-grade prostate intraepithelial neoplasia to metastasis. Urol Oncol 31:796–801

    Article  CAS  PubMed  Google Scholar 

  • Ley TJ, Ding L, Walter MJ, McLellan MD, Lamprecht T, Larson DE, Kandoth C, Payton JE, Baty J, Welch J et al (2010) DNMT3A mutations in acute myeloid leukemia. N Engl J Med 363:2424–2433

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Li LC, Carroll PR, Dahiya R (2005) Epigenetic changes in prostate cancer: implication for diagnosis and treatment. J Natl Cancer Inst 97:103–115

    Article  CAS  PubMed  Google Scholar 

  • Liloglou T, Bediaga NG, Brown BR, Field JK, Davies MP (2014) Epigenetic biomarkers in lung cancer. Cancer Lett 342:200–212

    Article  CAS  PubMed  Google Scholar 

  • Liu WB, Ao L, Cui ZH, Zhou ZY, Zhou YH, Yuan XY, Xiang YL, Cao J, Liu JY (2011a) Molecular analysis of DNA repair gene methylation and protein expression during chemical-induced rat lung carcinogenesis. Biochem Biophys Res Commun 408:595–601

    Article  CAS  PubMed  Google Scholar 

  • Liu X, Zhang Z, Sun L, Chai N, Tang S, Jin J, Hu H, Nie Y, Wang X, Wu K, Jin H, Fan D (2011b) MicroRNA-499-5p promotes cellular invasion and tumor metastasis in colorectal cancer by targeting FOXO4 and PDCD4. Carcinogenesis 32:1798–1805

    Article  CAS  PubMed  Google Scholar 

  • Lopez-Serra P, Esteller M (2012) DNA methylation-associated silencing of tumor-suppressor microRNAs in cancer. Oncogene 31:1609–1622

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Luo W, Chang R, Zhong J, Pandey A, Semenza GL (2012) Histone demethylase JMJD2C is a coactivator for hypoxia-inducible factor 1 that is required for breast cancer progression. Proc Natl Acad Sci U S A 109:E3367–E3376

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ma L, Teruya-Feldstein J, Weinberg RA (2007) Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 449:682–688

    Article  CAS  PubMed  Google Scholar 

  • Macphee DG (1998) Epigenetics and epimutagens: some new perspectives on cancer, germ line effects and endocrine disrupters. Mutat Res 400:369–379

    Article  CAS  PubMed  Google Scholar 

  • Madrigano J, Baccarelli A, Mittleman MA, Wright RO, Sparrow D, Vokonas PS, Tarantini L, Schwartz J (2011) Prolonged exposure to particulate pollution, genes associated with glutathione pathways and DNA methylation in a cohort of older men. Environ Health Perspect 119:977–982

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Majumdar S, Buckles E, Estrada J, Koochekpour S (2011) Aberrant DNA methylation and prostate cancer. Curr Genomics 12:486–505

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Menigatti M, Truninger K, Gebbers JO, Marbet U, Marra G, Schär P (2009) Normal colorectal mucosa exhibits sex- and segment-specific susceptibility to DNA methylation at the hMLH1 and MGMT promoters. Oncogene 28:899–909

    Article  CAS  PubMed  Google Scholar 

  • Migheli F, Migliore L (2012) Epigenetics of colorectal cancer. Clin Genet 81:312–318

    Article  CAS  PubMed  Google Scholar 

  • Mokarram P, Kumar K, Brim H, Naghibalhossaini F, Saberifiroozi M, Nouraie M, Green R, Lee E, Smoot DT, Ashktorab H (2009) Distinct high-profile methylated genes in colorectal cancer. PLoS One 4:e7012

    Article  PubMed Central  PubMed  Google Scholar 

  • Morin RD, Mendez-Lago M, Mungall AJ, Goya R, Mungall KL, Corbett RD, Johnson NA, Severson TM, Chiu R, Field M, Jackman S, Krzywinski M, Scott DW, Trinh DL, Tamura-Wells J, Li S, Firme MR, Rogic S, Griffith M, Chan S, Yakovenko O, Meyer IM, Zhao EY, Smailus D, Moksa M, Chittaranjan S, Rimsza L, Brooks-Wilson A, Spinelli JJ, Ben-Neriah S, Meissner B, Woolcock B, Boyle M, Mcdonald H, Tam A, Zhao Y, Delaney A, Zeng T, Tse K, Butterfield Y, Birol I, Holt R, Schein J, Horsman DE, Moore R, Jones SJ, Connors JM, Hirst M, Gascoyne RD, Marra MA (2011) Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature 476:298–303

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Nair SS, Kumar R (2012) Chromatin remodelling in cancer: a gateway to regulate gene transcription. Mol Oncol 6:611–619

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Nosho K, Kawasaki T, Ohnishi M, Suemoto Y, Kirkner GJ, Zepf D, Yan L, Longtine JA, Fuchs CS, Ogino S (2008) PIK3CA mutation in colorectal cancer: relationship with genetic and epigenetic alterations. Neoplasia 10:534–541

    CAS  PubMed Central  PubMed  Google Scholar 

  • Oberg AL, French AJ, Sarver AL, Subramanian S, Morlan BW, Riska SM, Borralho PM, Cunningham JM, Boardman LA, Wang L, Smyrk TC, Asmann Y, Steer CJ, Thibodeau SN (2011) miRNA expression in colon polyps provides evidence for a multihit model of colon cancer. PLoS One 6:e20465

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ogino S, Kawasaki T, Kirkner GJ, Suemoto Y, Meyerhardt JA, Fuchs CS (2007) Molecular correlates with MGMT promoter methylation and silencing support CpG island methylator phenotype-low (CIMP-low) in colorectal cancer. Gut 56:1564–1571

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • O’Hagan HM, Wang W, Sen S, Desthhefano Shields C, Lee SS, Zhang YW, Clements EG, Cai Y, Van Neste L, Easwaran H, Casero RA, Sears CL, Baylin SB (2011) Oxidative damage targets complexes containing DNA methyltransferases, SIRT1, and polycomb members to promoter CpG Islands. Cancer Cell 20:606–619

    Article  PubMed Central  PubMed  Google Scholar 

  • Pancione M, Remo A, Colantuoni V (2012) Genetic and epigenetic events generate multiple pathways in colorectal cancer progression. Pathol Res Int 2012:509348

    Article  Google Scholar 

  • Paolicchi E, Crea F, Farrar WL, Green JE, Danesi R (2013) Histone lysine demethylases in breast cancer. Crit Rev Oncol Hematol 86:97–103

    Article  PubMed Central  PubMed  Google Scholar 

  • Rao X, Evans J, Chae H, Pilrose J, Kim S, Yan P, Huang RL, Lai HC, Lin H, Liu Y, Miller D, Rhee JK, Huang YW, Gu F, Gray JW, Huang TM, Nephew KP (2012) CpG island shore methylation regulates caveolin-1 expression in breast cancer. Oncogene. doi:10.1038/onc.2012.474

    Google Scholar 

  • Rodríguez-Paredes M, Esteller M (2011) Cancer epigenetics reaches mainstream oncology. Nat Med 17:330–339

    Article  PubMed  Google Scholar 

  • Sadikovic B, Al-Romaih K, Squire JA, Zielenska M (2008) Cause and consequences of genetic and epigenetic alterations in human cancer. Curr Genomics 9:394–408

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sandoval J, Esteller M (2012) Cancer epigenomics: beyond genomics. Curr Opin Genet Dev 22:50–55

    Article  CAS  PubMed  Google Scholar 

  • Schernhammer ES, Giovannucci E, Kawasaki T, Rosner B, Fuchs CS, Ogino S (2010) Dietary folate, alcohol and B vitamins in relation to LINE-1 hypomethylation in colon cancer. Gut 59:794–799

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • 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 60:1687–1694

    Article  CAS  PubMed  Google Scholar 

  • Slaga TJ (1984) Multistage skin carcinogenesis: a useful model for the study of the chemoprevention of cancer. Acta Pharmacol Toxicol (Copenh) 55:107–124

    Article  CAS  Google Scholar 

  • Suzuki H, Maruyama R, Yamamoto E, Kai M (2012) DNA methylation and microRNA dysregulation in cancer. Mol Oncol 6:567–578

    Article  CAS  PubMed  Google Scholar 

  • Tarantini L, Bonzini M, Apostoli P, Pegoraro V, Bollati V, Marinelli B, Cantone L, Rizzo G, Hou L, Schwartz J, Bertazzi PA, Baccarelli A (2009) Effects of particulate matter on genomic DNA methylation content and iNOS promoter methylation. Environ Health Perspect 117:217–222

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Terry MB, Delgado-Cruzata L, Vin-Raviv N, Wu HC, Santella RM (2011) DNA methylation in white blood cells: association with risk factors in epidemiologic studies. Epigenetics 6:828–837

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tserga A, Michalopoulos NV, Levidou G, Korkolopoulou P, Zografos G, Patsouris E, Saetta AA (2012) Association of aberrant DNA methylation with clinicopathological features in breast cancer. Oncol Rep 27:1630–1638

    CAS  PubMed  Google Scholar 

  • Tyler JK, Kadonaga JT (1999) The “dark side” of chromatin remodeling: repressive effects on transcription. Cell 99:443–446

    Article  CAS  PubMed  Google Scholar 

  • van Engeland M, Derks S, Smits KM, Meijer GA, Herman JG (2011) Colorectal cancer epigenetics: complex simplicity. J Clin Oncol 29:1382–1391

    Article  PubMed  Google Scholar 

  • Vineis P, Schatzkin A, Potter JD (2010) Models of carcinogenesis: an overview. Carcinogenesis 31:1703–1709

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Whitehouse A, Meredith DM, Markham AF (1998) DNA mismatch repair genes and their association with colorectal cancer (Review). Int J Mol Med 1:469–474

    CAS  PubMed  Google Scholar 

  • You JS, Jones PA (2012) Cancer genetics and epigenetics: two sides of the same coin? Cancer Cell 22:9–20

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Translational Research and New Technologies in Medicine and Surgery, Division of Medical Genetics, University of Pisa, Via S. Maria 55, 56126, Pisa, Italy

    Francesca Migheli & Lucia Migliore

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  1. Francesca Migheli
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  2. Lucia Migliore
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Correspondence to Lucia Migliore .

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  1. Department of Surgery Molecular cardiology and Angiogenesis, University of Connecticut School of Medicine, Farmington, Connecticut, USA

    Nilanjana Maulik

  2. Epigenomic Medicine, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia

    Tom Karagiannis

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Migheli, F., Migliore, L. (2014). Epigenetic Perturbations in the Context of the Multi-hit Hypothesis of Carcinogenesis. 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_14

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