Molecular pathological epidemiology of epigenetics: Emerging integrative science to analyze environment, host, and disease

Modern Pathology

Volumn 26, Issue 4, 2013, Pages 465-484

  Ogino, Shuji ^a,b,c   Lochhead, Paul ^c,d   Chan, Andrew T ^e,f   Nishihara, Reiko ^c   Cho, Eunyoung ^f   Wolpin, Brian M ^c   Meyerhardt, Jeffrey A ^c   Meissner, Alexander ^g   Schernhammer, Eva S ^b,f   Fuchs, Charles S ^c,f   Giovannucci, Edward ^b,f  

^a HARVARD MEDICAL SCHOOL   (United States)

^b HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

^c DANA FARBER CANCER INSTITUTE   (United States)

^d UNIVERSITY OF ABERDEEN   (United Kingdom)

^e MASSACHUSETTS GENERAL HOSPITAL   (United States)

^f BRIGHAM AND WOMEN S HOSPITAL   (United States)

^g BROAD INSTITUTE OF MIT AND HARVARD   (United States)

Author keywords

CIMP; genetics; hypermethylation; molecular pathological epidemiology; omics; personalized therapy; unique tumor principle

Indexed keywords

ACETYLSALICYLIC ACID; PROTEOME; TRANSCRIPTOME;

BODY FLUID; CANCER GENETICS; CELL HETEROGENEITY; COLORECTAL CANCER; CPG ISLAND; EARLY DIAGNOSIS; ENVIRONMENTAL FACTOR; EPIGENETICS; GENOME; GENOME ANALYSIS; GENOTYPE; HUMAN; IMMUNITY; INFLAMMATION; METABOLOME; METHYLATION; MICROBIOME; MOLECULAR EPIDEMIOLOGY; PERSONALIZED MEDICINE; PRIORITY JOURNAL; REVIEW; SMOKING;

EPIDEMIOLOGY; EPIGENOMICS; HUMANS; INDIVIDUALIZED MEDICINE; PATHOLOGY, MOLECULAR;

EID: 84876470674     PISSN: 08933952     EISSN: 15300285     Source Type: Journal    
DOI: 10.1038/modpathol.2012.214     Document Type: Review

References (379)

1. Baylin SB, Jones PA. A decade of exploring the cancer epigenome-biological and translational implications. Nat Rev Cancer 2011;11:726-734.
2. Jones PA. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet 2012;13:484-492.
3. Park J, Xu K, Park T, et al. What are the determinants of gene expression levels and breadths in the human genome? Hum Mol Genet 2012;21:46-56.
4. Rodriguez-Paredes M, Esteller M. Cancer epigenetics reaches mainstream oncology. Nat Med 2011;17: 330-339.
5. Juergens RA, Wrangle J, Vendetti FP, et al. Combination epigenetic therapy has efficacy in patients with refractory advanced non-small cell lung cancer. Cancer Discov 2011;1:598-607.
6. Ebert MP, Tanzer M, Balluff B, et al. TFAP2E-DKK4 and chemoresistance in colorectal cancer. N Engl J Med 2012;366:44-53.
7. de Krijger I, Mekenkamp LJ, Punt CJ, et al. Micro-RNAs in colorectal cancer metastasis. J Pathol 2011;224:438-447.
8. Wang F, Ma YL, Zhang P, et al. SP1 mediates the link between methylation of the tumour suppressor miR-149 and outcome in colorectal cancer. J Pathol 2013;229:12-24.
9. Valeri N, Gasparini P, Fabbri M, et al. Modulation of mismatch repair and genomic stability by miR-155. Proc Natl Acad Sci USA 2010;107:6982-6987.
10. Valeri N, Gasparini P, Braconi C, et al. MicroRNA-21 induces resistance to 5-fluorouracil by down-regulating human DNA MutS homolog 2 (hMSH2). Proc Natl Acad Sci USA 2010;107:21098-21103.
11. Bartley AN, Yao H, Barkoh BA, et al. Complex patterns of altered microRNA expression during the adenoma-adenocarcinoma sequence for microsatel-lite- stable colorectal cancer. Clin Cancer Res 2011; 17:7283-7293.
12. Earle JS, Luthra R, Romans A, et al. Association of microRNA expression with microsatellite instability status in colorectal adenocarcinoma. J Mol Diagn 2010;12:433-440.
13. Alhopuro P, Sammalkorpi H, Niittymaki I, et al. Candidate driver genes in microsatellite-unstable colorectal cancer. Int J Cancer 2012;130:1558-1566.
14. Waldron L, Ogino S, Hoshida Y, et al. Expression profiling of archival tissues for long-term health studies. Clin Cancer Res 2012;18:6136-6146.
15. Stein RA. Epigenetics-the link between infectious diseases and cancer. JAMA 2011;305:1484-1485.
16. Coppede F. Epigenetic biomarkers of colorectal cancer: focus on DNA methylation. Cancer Lett 2012; in press (published online).
17. Kostic AD, Gevers D, Pedamallu CS, et al. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res 2012;22:292-298.
18. Castellarin M, Warren RL, Freeman JD, et al. Fuso-bacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res 2012;22:299-306.
19. Cho I, Blaser MJ. The human microbiome: at the interface of health and disease. Nat Rev Genet 2012;13:260-270.
20. Tjalsma H, Boleij A, Marchesi JR, et al. A bacterial driver-passenger model for colorectal cancer: beyond the usual suspects. Nat Rev Microbiol 2012;10:575-582.
21. Ogino S, Stampfer M. Lifestyle factors and micro-satellite instability in colorectal cancer: the evolving field of molecular pathological epidemiology. J Natl Cancer Inst 2010;102:365-367.
22. Ogino S, Chan AT, Fuchs CS, et al. Molecular pathological epidemiology of colorectal neoplasia: an emerging transdisciplinary and interdisciplinary field. Gut 2011;60:397-411.
23. Ogino S, Galon J, Fuchs CS, et al. Cancer immunology-analysis of host and tumor factors for personalized medicine. Nat Rev Clin Oncol 2011;8:711-719.
24. Baccarelli A, Wright R, Bollati V, et al. Ischemic heart disease and stroke in relation to blood DNA methyla-tion. Epidemiology 2010;21:819-828.
25. Bind M, Baccarelli A, Zanobetti A, et al. Air pollution and markers of coagulation, inflammation, and endothelial function: associations and epigene-environment interactions in an elderly cohort. Epidemiology 2012;23:332-340.
26. Tang WY, Levin L, Talaska G, et al. Maternal exposure to polycyclic aromatic hydrocarbons and 5-CpG methylation of interferon-gamma in cord white blood cells. Environ Health Perspect 2012;120:1195-1200.
27. Flom JD, Ferris JS, Liao Y, et al. Prenatal smoke exposure and genomic DNA methylation in a multiethnic birth cohort. Cancer Epidemiol Biomarkers Prev 2011;20:2518-2523.
28. Hernandez DG, Nalls MA, Gibbs JR, et al. Distinct DNA methylation changes highly correlated with chronological age in the human brain. Hum Mol Genet 2011;20:1164-1172.
29. Wan ES, Qiu W, Baccarelli A, et al. Cigarette smoking behaviors and time since quitting are associated with differential DNA methylation across the human genome. Hum Mol Genet 2012;21:3073-3082.
30. Dempster EL, Pidsley R, Schalkwyk LC, et al. Disease-associated epigenetic changes in monozygo-tic twins discordant for schizophrenia and bipolar disorder. Hum Mol Genet 2011;20:4786-4796.
31. Ollikainen M, Smith KR, Joo EJ, et al. DNA methyla-tion analysis of multiple tissues from newborn twins reveals both genetic and intrauterine components to variation in the human neonatal epigenome. Hum Mol Genet 2010;19:4176-4188.
32. Byun HM, Siegmund KD, Pan F, et al. Epigenetic profiling of somatic tissues from human autopsy specimens identifies tissue-and individual-specific DNA methylation patterns. Hum Mol Genet 2009;18:4808-4817.
33. Toperoff G, Aran D, Kark JD, et al. Genome-wide survey reveals predisposing diabetes type 2-related DNA methylation variations in human peripheral blood. Hum Mol Genet 2012;21:371-383.
34. Lambrou A, Baccarelli A, Wright RO, et al. Arsenic exposure and DNA methylation among elderly men. Epidemiology 2012;23:668-676.
35. Huang WY, Su LJ, Hayes RB, et al. Prospective study of genomic hypomethylation of leukocyte DNA and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev 2012;21:2014-2021.
36. Gao Y, Killian K, Zhang H, et al. Leukocyte DNA methylation and colorectal cancer among male smokers. World J Gastrointest Oncol 2012;4:193-201.
37. Marusyk A, Almendro V, Polyak K. Intra-tumor heterogeneity: a looking glass for cancer. Nat Rev Cancer 2012;12:323-334.
38. Thomas DC, Lewinger JP, Murcray CE, et al. Invited commentary: GE-Whiz! Ratcheting gene-environment studies up to the whole genome and the whole exposome. Am J Epidemiol 2012;175: 203-207; discussion 208-209.
39. Curtin K, Slattery ML, Samowitz WS. CpG island methylation in colorectal cancer: past, present and future. Pathology Res Int 2011;2011:902674.
40. Hughes LA, Simons CC, van den Brandt PA, et al. Body size, physical activity and risk of colorectal cancer with or without the CpG island methylator phenotype (CIMP). PLoS One 2011;6:e18571.
41. Kelley RK, Wang G, Venook AP. Biomarker use in colorectal cancer therapy. J Natl Compr Canc Netw 2011;9:1293-1302.
42. Campbell PT, Newton CC, Dehal AN, et al. Impact of body mass index on survival after colorectal cancer diagnosis: The Cancer Prevention Study-II Nutrition Cohort. J Clin Oncol 2012;30:42-52.
43. Gehoff A, Basten O, Sprenger T, et al. Optimal lymph node harvest in rectal cancer (UICC Stages II and III) after preoperative 5-FU-based radiochemotherapy. acetone compression is a new and highly efficient method. Am J Surg Pathol 2012;36:202-213.
44. Hughes LA, Khalid-de Bakker CA, Smits KM, et al. The CpG island methylator phenotype in colorectal cancer: Progress and problems. Biochim Biophys Acta 2012;1825:77-85.
45. Iwagami S, Baba Y, Watanabe M, et al. Pyrosequen-cing assay to measure LINE-1 methylation level in esophageal squamous cell carcinoma. Ann Surg Oncol 2012;19:2726-2732.
46. Esteban S, Moya P, Fernandez-Suarez A, et al. Diagnostic and prognostic utility of methylation and protein expression patterns of myopodin in colon cancer. Tumour Biol 2012;33:337-346.
47. Limburg PJ, Limsui D, Vierkant RA, et al. Postmeno-pausal hormone therapy and colorectal cancer risk in relation to somatic KRAS mutation status among older women. Cancer Epidemiol Biomarkers Prev 2012;21:681-684.
48. Limsui D, Vierkant RA, Tillmans LS, et al. Post-menopausal hormone therapy and colorectal cancer risk by molecularly defined subtypes among older women. Gut 2012;61:1299-1305.
49. Hughes LA, Williamson EJ, van Engeland M, et al. Body size and risk for colorectal cancers showing BRAF mutation or microsatellite instability: a pooled analysis. Int J Epidemiol 2012;41:1060-1072.
50. Ku CS, Cooper DN, Wu M, et al. Gene discovery in familial cancer syndromes by exome sequencing: prospects for the elucidation of familial colorectal cancer type X. Mod Pathol 2012;25:1055-1068.
51. Kanthan R, Senger JL, Kanthan SC. Molecular events in primary and metastatic colorectal carcinoma: a review. Pathol Res Int 2012;2012:597497.
52. Rex DK, Ahnen DJ, Baron JA, et al. Serrated lesions of the colorectum: review and recommendations from an expert panel. Am J Gastroenterol 2012;107: 1315-1329.
53. Koshiol J, Lin SW. Can tissue-based immune markers be used for studying the natural history of cancer? Ann Epidemiol 2012;22:520-530.
54. Patai AV, Molnar B, Kalmar A, et al. Role of DNA methylation in colorectal carcinogenesis. Dig Dis 2012;30:310-315.
55. Fini L, Grizzi F, Laghi L. Adaptive and innate immunity, non clonal players in colorectal cancer progression, In: Ettarh R (ed). Colorectal Cancer Biology-From Genes to Tumor. InTech, 2012, pp 323-340.
56. Gay LJ, Mitrou PN, Keen J, et al. Dietary, lifestyle and clinico-pathological factors associated with APC mutations and promoter methylation in colorectal cancers from the EPIC-Norfolk Study. J Pathol 2012;228:405-415.
57. Chia WK, Ali R, Toh HC. Aspirin as adjuvant therapy for colorectal cancer-reinterpreting paradigms. Nat Rev Clin Oncol 2012;9:561-570.
58. Dogan S, Shen R, Ang DC, et al. Molecular epidemiology of EGFR and KRAS mutations in 3026 lung adenocarcinomas: higher susceptibility of women to smoking-related KRAS-mutant cancers. Clin Cancer Res 2012;18:6169-6177.
59. Galon J, Franck P, Marincola FM, et al. Cancer classification using the Immunoscore: a worldwide task force. J Transl Med 2012;10:205.
60. Haq S, Ali S, Mohammad R, et al. The complexities of epidemiology and prevention of gastrointestinal cancers. Int J Mol Sci 2012;13:12556-12572.
61. Boyle T, Fritschi L, Heyworth J, et al. Long-term sedentary work and the risk of subsite-specific colorectal cancer. Am J Epidemiol 2011;173: 1183-1191.
62. Jacobs R, Voorneveld P, Kodach L, et al. Cholesterol metabolism and colorectal cancers. Curr Opin Pharmacol 2012;12:690-695.
63. Ogino S, Giovannucci E. Commentary: lifestyle factors and colorectal cancer microsatellite instability-molecular pathological epidemiology science, based on unique tumour principle. Int J Epidemiol 2012;41:1072-1074.
64. Ogino S, Fuchs CS, Giovannucci E. How many molecular subtypes? Implications of the unique tumor principle in personalized medicine. Expert Rev Mol Diagn 2012;12:621-628.
65. Ogino S, King EE, Beck AH, et al. Interdisciplinary education to integrate pathology and epidemiology: towards molecular and population-level health science. Am J Epidemiol 2012;176:659-667.
66. Ogino S, Beck AH, King EE, et al. Ogino et al. respond to 'The 21st century epidemiologist'. Am J Epidemiol 2012;176:672-674.
67. Begg CB, Zabor EC. Detecting and exploiting etiologic heterogeneity in epidemiologic studies. Am J Epidemiol 2012;176:512-518.
68. Ghosh S, Matsuoka Y, Asai Y, et al. Software for systems biology: from tools to integrated platforms. Nat Rev Genet 2011;12:821-832.
69. Papp B, Notebaart RA, Pal C. Systems-biology approaches for predicting genomic evolution. Nat Rev Genet 2011;12:591-602.
70. Ogino S, Nosho K, Meyerhardt JA, et al. Cohort study of fatty acid synthase expression and patient survival in colon cancer. J Clin Oncol 2008;26:5713-5720.
71. Chan AT, Ogino S, Fuchs CS. Aspirin use and survival after diagnosis of colorectal cancer. JAMA 2009;302:649-658.
72. Morikawa T, Kuchiba A, Yamauchi M, et al. Association of CTNNB1 (beta-catenin) alterations, body mass index, and physical activity with survival in patients with colorectal cancer. JAMA 2011; 305:1685-1694.
73. Liao X, Lochhead P, Nishihara R, et al. Aspirin use, tumor PIK3CA mutation status, and colorectal cancer survival. N Engl J Med 2012;367:1596-1606.
74. Pasche B. Aspirin-from prevention to targeted therapy. N Engl J Med 2012;367:1650-1651.
75. Begg CB. A strategy for distinguishing optimal cancer subtypes. Int J Cancer 2011;129:931-937.
76. Ogino S, Goel A. Molecular classification and correlates in colorectal cancer. J Mol Diagn 2008;10: 13-27. (Pubitemid 351184831)
77. Toyota M, Ahuja N, Ohe-Toyota M, et al. CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci USA 1999;96:8681-8686. (Pubitemid 29354851)
78. Sproul D, Kitchen RR, Nestor CE, et al. Tissue of origin determines cancer-associated CpG island promoter hypermethylation patterns. Genome Biol 2012;13:R84.
79. Noushmehr H, Weisenberger DJ, Diefes K, et al. Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell 2010;17:510-522.
80. Turcan S, Rohle D, Goenka A, et al. IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Nature 2012;483:479-483.
81. Shinjo K, Okamoto Y, An B, et al. Integrated analysis of genetic and epigenetic alterations reveals CpG island methylator phenotype associated with distinct clinical characters of lung adenocarcinoma. Carcino-genesis 2012;33:1277-1285.
82. The Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature 2011;474:609-615.
83. Kolbe DL, Deloia JA, Porter-Gill P, et al. Differential analysis of ovarian and endometrial cancers identifies a methylator phenotype. PLoS One 2012; 7:e32941.
84. Ueki T, Toyota M, Sohn T, et al. Hypermethylation of multiple genes in pancreatic adenocarcinoma. Cancer Res 2000;60:1835-1839. (Pubitemid 30207640)
85. Suzuki M, Shigematsu H, Iizasa T, et al. Exclusive mutation in epidermal growth factor receptor gene, HER-2, and KRAS, and synchronous methylation of nonsmall cell lung cancer. Cancer 2006;106: 2200-2207. (Pubitemid 43673242)
86. Shaw RJ, Hall GL, Lowe D, et al. CpG island methylation phenotype (CIMP) in oral cancer: associated with a marked inflammatory response and less aggressive tumour biology. Oral Oncol 2007;43: 878-886. (Pubitemid 47369250)
87. Tanemura A, Terando AM, Sim MS, et al. CpG island methylator phenotype predicts progression of malignant melanoma. Clin Cancer Res 2009;15:1801-1807.
88. Toyota M, Ahuja N, Suzuki H, et al. Aberrant methylation in gastric cancer associated with the CpG island methylator phenotype. Cancer Res 1999; 59:5438-5442. (Pubitemid 29526452)
89. Fang F, Turcan S, Rimner A, et al. Breast cancer methylomes establish an epigenomic foundation for metastasis. Sci Transl Med 2011;3:75ra25.
90. Warth A, Kloor M, Schirmacher P, et al. Genetics and epigenetics of small bowel adenocarcinoma: the interactions of CIN, MSI, and CIMP. Mod Pathol 2011;24:564-570.
91. Abe M, Watanabe N, McDonell N, et al. Identification of genes targeted by CpG island methylator pheno-type in neuroblastomas, and their possible integrative involvement in poor prognosis. Oncology 2008; 74:50-60. (Pubitemid 351915010)
92. Yagi K, Takahashi H, Akagi K, et al. Intermediate methylation epigenotype and its correlation to KRAS mutation in conventional colorectal adenoma. Am J Pathol 2012;180:616-625.
93. Duncan CG, Barwick BG, Jin G, et al. A heterozygous IDH1R132H/WT mutation induces genome-wide alterations in DNA methylation. Genome Res 2012; 22:2339-2355.
94. Park SY, Kwon HJ, Choi Y, et al. Distinct patterns of promoter CpG island methylation of breast cancer subtypes are associated with stem cell phenotypes. Mod Pathol 2012;25:185-196.
95. Zouridis H, Deng N, Ivanova T, et al. Methylation subtypes and large-scale epigenetic alterations in gastric cancer. Sci Transl Med 2012;4:156ra140.
96. Yamamoto E, Suzuki H, Yamano HO, et al. Molecular dissection of premalignant colorectal lesions reveals early onset of the CpG island methylator phenotype. Am J Pathol 2012;181:1847-1861.
97. Lao VV, Grady WM. Epigenetics and colorectal cancer. Nat Rev Gastroenterol Hepatol 2011;8: 686-700.
98. Greystoke A, Mullamitha SA. How many diseases is colorectal cancer? Gastroenterol Res Pract 2012;2012:564741.
99. Beggs AD, Jones A, El-Bahwary M, et al. Whole-genome methylation analysis of benign and malignant colorectal tumours. J Pathol 2013 (in press).
100. Samowitz W, Albertsen H, Herrick J, et al. Evaluation of a large, population-based sample supports a CpG island methylator phenotype in colon cancer. Gastro-enterology 2005;129:837-845. (Pubitemid 41242676)
101. Ogino S, Cantor M, Kawasaki T, et al. CpG island methylator phenotype (CIMP) of colorectal cancer is best characterised by quantitative DNA methylation analysis and prospective cohort studies. Gut 2006;55:1000-1006. (Pubitemid 43962613)
102. Weisenberger DJ, Siegmund KD, Campan M, et al. CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet 2006;38:787-793. (Pubitemid 43980599)
103. Nosho K, Irahara N, Shima K, et al. Comprehensive biostatistical analysis of CpG island methylator phenotype in colorectal cancer using a large population-based sample. PLoS ONE 2008;3:e3698.
104. The Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature 2012;487:330-337.
105. Gazin C, Wajapeyee N, Gobeil S, et al. An elaborate pathway required for Ras-mediated epigenetic silencing. Nature 2007;449:1073-1077. (Pubitemid 350014604)
106. Hinoue T, Weisenberger DJ, Pan F, et al. Analysis of the association between CIMP and BRAF in colorectal cancer by DNA methylation profiling. PLoS One 2009;4:e8357.
107. Lin H, Yamada Y, Nguyen S, et al. Suppression of intestinal neoplasia by deletion of Dnmt3b. Mol Cell Biol 2006;26:2976-2983.
108. Linhart HG, Lin H, Yamada Y, et al. Dnmt3b promotes tumorigenesis in vivo by gene-specific de novo methylation and transcriptional silencing. Genes Dev 2007;21:3110-3122. (Pubitemid 350223528)
109. Palakurthy RK, Wajapeyee N, Santra MK, et al. Epigenetic silencing of the RASSF1A tumor suppressor gene through HOXB3-mediated induction of DNMT3B expression. Mol Cell 2009;36:219-230.
110. Nosho K, Shima K, Irahara N, et al. DNMT3B expression might contribute to CpG island methylator phenotype in colorectal cancer. Clin Cancer Res 2009;15:3663-3671.
111. Ibrahim AE, Arends MJ, Silva AL, et al. Sequential DNA methylation changes are associated with DNMT3B overexpression in colorectal neoplastic progression. Gut 2011;60:499-508.
112. Steine EJ, Ehrich M, Bell GW, et al. Genes methylated by DNA methyltransferase 3b are similar in mouse intestine and human colon cancer. J Clin Invest 2011;121:1748-1752.
113. Vaughn CP, Wilson AR, Samowitz WS. Quantitative evaluation of CpG island methylation in hyperplastic polyps. Mod Pathol 2010;23:151-156.
114. Huang CS, Farraye FA, Yang S, et al. The clinical significance of serrated polyps. Am J Gastroenterol 2011;106:229-240.
115. Snover DC. Update on the serrated pathway to colorectal carcinoma. Hum Pathol 2011;42:1-10.
116. Patil DT, Shadrach BL, Rybicki LA, et al. Proximal colon cancers and the serrated pathway: a systematic analysis of precursor histology and BRAF mutation status. Mod Pathol 2012;25:1423-1431.
117. Kriegl L, Neumann J, Vieth M, et al. Up and down-regulation of p16(Ink4a) expression in BRAF-mutated polyps/adenomas indicates a senescence barrier in the serrated route to colon cancer. Mod Pathol 2011;24:1015-1022.
118. Ogino S, Kawasaki T, Kirkner GJ, et al. CpG island methylator phenotype-low (CIMP-low) in colorectal cancer: possible associations with male sex and KRAS mutations. J Mol Diagn 2006;8:582-588. (Pubitemid 44774157)
119. Shen L, Toyota M, Kondo Y, et al. Integrated genetic and epigenetic analysis identifies three different subclasses of colon cancer. Proc Natl Acad Sci USA 2007;104:18654-18659. (Pubitemid 350210752)
120. Ogino S, Kawasaki T, Kirkner GJ, et al. Molecular correlates with MGMT promoter methylation and silencing support CpG island methylator phenotype-low (CIMP-low) in colorectal cancer. Gut 2007;56:1409-1416.
121. Barault L, Charon-Barra C, Jooste V, et al. Hyper-methylator phenotype in sporadic colon cancer: study on a population-based series of 582 cases. Cancer Res 2008;68:8541-8546.
122. Kim JH, Shin SH, Kwon HJ, et al. Prognostic implications of CpG island hypermethylator pheno-type in colorectal cancers. Virchows Arch 2009; 455:485-494.
123. Dahlin AM, Palmqvist R, Henriksson ML, et al. The role of the CpG island methylator phenotype in colorectal cancer prognosis depends on microsatellite instability screening status. Clin Cancer Res 2010; 16:1845-1855.
124. Van Guelpen B, Dahlin AM, Hultdin J, et al. One-carbon metabolism and CpG island methylator phe-notype status in incident colorectal cancer: a nested case-referent study. Cancer Causes Control 2010; 21:557-566.
125. Tanaka N, Huttenhower C, Nosho K, et al. Novel application of structural equation modeling to correlation structure analysis of CpG island methyla-tion in colorectal cancer. Am J Pathol 2010;177: 2731-2740.
126. Karpinski P, Szmida E, Misiak B, et al. Assessment of three epigenotypes in colorectal cancer by combined bisulfite restriction analysis. Mol Carcinogen 2012;51:1003-1008.
127. Hinoue T, Weisenberger DJ, Lange CP, et al. Genome-scale analysis of aberrant DNA methylation in color-ectal cancer. Genome Res 2012;22:271-282.
128. Zlobec I, Bihl MP, Foerster A, et al. Stratification and prognostic relevance of Jass's molecular classification of colorectal cancer. Front Oncol 2012;2:7.
129. Imamura Y, Morikawa T, Liao X, et al. Specific mutations in KRAS codons 12 and 13, and patient prognosis in 1075 BRAF-wild-type colorectal cancers. Clin Cancer Res 2012;18:4753-4763.
130. Kawasaki T, Ohnishi M, Nosho K, et al. CpG island methylator phenotype-low (CIMP-low) colorectal cancer shows not only few methylated CIMP-high-specific CpG islands, but also low-level methylation at individual loci. Mod Pathol 2008;21:245-255. (Pubitemid 351304277)
131. Yagi K, Akagi K, Hayashi H, et al. Three DNA methylation epigenotypes in human colorectal cancer. Clin Cancer Res 2010;16:21-33.
132. Ogino S, Nosho K, Kirkner GJ, et al. CpG island methylator phenotype, microsatellite instability, BRAF mutation and clinical outcome in colon cancer. Gut 2009;58:90-96.
133. Liao X, Morikawa T, Lochhead P, et al. Prognostic role of PIK3CA mutation in colorectal cancer: cohort study and literature review. Clin Cancer Res 2012;18:2257-2268.
134. Whitehall VL, Rickman C, Bond CE, et al. Oncogenic PIK3CA mutations in colorectal cancers and polyps. Int J Cancer 2012;131:813-820.
135. Ogino S, Meyerhardt JA, Kawasaki T, et al. CpG island methylation, response to combination chemotherapy, and patient survival in advanced micro-satellite stable colorectal carcinoma. Virchows Arch 2007;450:529-537. (Pubitemid 46676250)
136. Teodoridis JM, Hardie C, Brown R. CpG island methylator phenotype (CIMP) in cancer: Causes and implications. Cancer Lett 2008;268:177-186.
137. Wu C, Bekaii-Saab T. CpG island methylation, microsatellite instability, and BRAF mutations and their clinical application in the treatment of colon cancer. Chemother Res Pract 2012;2012:359041.
138. Jover R, Nguyen TP, Perez-Carbonell L, et al. 5-Fluorouracil adjuvant chemotherapy does not increase survival in patients with CpG island methy-lator phenotype colorectal cancer. Gastroenterology 2011;140:1174-1181.
139. Van Rijnsoever M, Elsaleh H, Joseph D, et al. CpG island methylator phenotype is an independent predictor of survival benefit from 5-fluorouracil in stage III colorectal cancer. Clin Cancer Res 2003;9:2898-2903. (Pubitemid 36993247)
140. Wong JJ, Hawkins NJ, Ward RL, et al. Methylation of the 3p22 region encompassing MLH1 is representative of the CpG island methylator phenotype in colorectal cancer. Mod Pathol 2011;24:396-411.
141. Sanchez JA, Krumroy L, Plummer S, et al. Genetic and epigenetic classifications define clinical pheno-types and determine patient outcomes in colorectal cancer. Br J Surg 2009;96:1196-1204.
142. Yamauchi M, Morikawa T, Kuchiba A, et al. Assessment of colorectal cancer molecular features along bowel subsites challenges the conception of distinct dichotomy of proximal versus distal colorectum. Gut 2012;61:847-854.
143. Chirieac LR, Shen L, Catalano PJ, et al. Phenotype of microsatellite-stable colorectal carcinomas with CpG island methylation. Am J Surg Pathol 2005;29: 429-436. (Pubitemid 40411172)
144. Ogino S, Odze RD, Kawasaki T, et al. Correlation of pathologic features with CpG island methylator phenotype (CIMP) by quantitative DNA methylation analysis in colorectal carcinoma. Am J Surg Pathol 2006;30:1175-1183. (Pubitemid 44299351)
145. Kawasaki T, Ohnishi M, Suemoto Y, et al. WRN promoter methylation possibly connects mucinous differentiation, microsatellite instability and CpG island methylator phenotype in colorectal cancer. Mod Pathol 2008;21:150-158. (Pubitemid 351172166)
146. Kakar S, Deng G, Smyrk TC, et al. Loss of hetero-zygosity, aberrant methylation, BRAF mutation and KRAS mutation in colorectal signet ring cell carcinoma. Mod Pathol 2012;25:1040-1047.
147. Nosho K, Baba Y, Tanaka N, et al. Tumour-infiltrating T-cell subsets, molecular changes in colorectal cancer and prognosis: cohort study and literature review. J Pathol 2010;222:350-366.
148. Dahlin AM, Henriksson ML, Van Guelpen B, et al. Colorectal cancer prognosis depends on T-cell infiltration and molecular characteristics of the tumor. Mod Pathol 2011;24:671-682.
149. Ogino S, Nosho K, Irahara N, et al. Lymphocytic reaction to colorectal cancer is associated with longer survival, independent of lymph node count, micro-satellite instability, and CpG island methylator phenotype. Clin Cancer Res 2009;15:6412-6420.
150. Ogino S, Brahmandam M, Kawasaki T, et al. Combined analysis of COX-2 and p53 expressions reveals synergistic inverse correlations with microsatellite instability and CpG island methylator phenotype in colorectal cancer. Neoplasia 2006;8:458-464. (Pubitemid 44035329)
151. Ogino S, Kawasaki T, Kirkner GJ, et al. Down-regulation of p21 (CDKN1A/CIP1) is inversely associated with microsatellite instability and CpG island methylator phenotype (CIMP) in colorectal cancer. J Pathol 2006;210:147-154. (Pubitemid 44463929)
152. Ogino S, kawasaki T, Kirkner GJ, et al. Loss of nuclear p27 (CDKN1B/KIP1) in colorectal cancer is correlated with microsatellite instability and CIMP. Mod Pathol 2007;20:15-22. (Pubitemid 44967945)
153. Kawasaki T, Nosho K, Ohnishi M, et al. Correlation of beta-catenin localization with cyclooxygenase-2 expression and CpG island methylator phenotype (CIMP) in colorectal cancer. Neoplasia 2007;9: 569-577. (Pubitemid 47121831)
154. Samowitz WS, Slattery ML, Sweeney C, et al. APC mutations and other genetic and epigenetic changes in colon cancer. Mol Cancer Res 2007;5:165-170. (Pubitemid 46423997)
155. Nosho K, Shima K, Irahara N, et al. SIRT1 histone deacetylase expression is associated with microsatel-lite instability and CpG island methylator phenotype in colorectal cancer. Mod Pathol 2009;22:922-932.
156. Baba Y, Nosho K, Shima K, et al. PTGER2 over-expression in colorectal cancer is associated with microsatellite instability, independent of CpG island methylator phenotype. Cancer Epidemiol Biomarkers Prev 2010;19:822-831.
157. Ogino S, Kawasaki T, Nosho K, et al. LINE-1 hypomethylation is inversely associated with micro-satellite instability and CpG methylator phenotype in colorectal cancer. Int J Cancer 2008;122:2767-2773. (Pubitemid 351631379)
158. Baba Y, Nosho K, Shima K, et al. Relationship of CDX2 loss with molecular features and prognosis in colorectal cancer. Clin Cancer Res 2009;15: 4665-4673.
159. Zlobec I, Bihl M, Foerster A, et al. Comprehensive analysis of CpG island methylator phenotype (CIMP)-high,-low, and-negative colorectal cancers based on protein marker expression and molecular features. J Pathol 2011;225:336-343.
160. Ogino S, Kawasaki T, Kirkner GJ, et al. 18q loss of heterozygosity in microsatellite stable colorectal cancer is correlated with CpG island methylator phenotype-negative (CIMP-0) and inversely with CIMP-low and CIMP-high. BMC Cancer 2007;7:72.
161. Goel A, Nagasaka T, Arnold CN, et al. The CpG island methylator phenotype and chromosomal instability are inversely correlated in sporadic colorectal cancer. Gastroenterology 2007;132:127-138. (Pubitemid 46108731)
162. Cheng YW, Pincas H, Bacolod MD, et al. CpG island methylator phenotype associates with low-degree chromosomal abnormalities in colorectal cancer. Clin Cancer Res 2008;14:6005-6013.
163. Kozlowska J, Karpinski P, Szmida E, et al. Assessment of chromosomal imbalances in CIMP-high and CIMP-low/CIMP-0 colorectal cancers. Tumour Biol 2012;33:1015-1019.
164. Morikawa T, Kuchiba A, Qian ZR, et al. Prognostic significance and molecular associations of tumor growth pattern in colorectal cancer. Ann Surg Oncol 2012;19:1944-1953.
165. Zlobec I, Bihl MP, Foerster A, et al. The impact of CpG island methylator phenotype and microsatellite instability on tumour budding in colorectal cancer. Histopathology 2012;61:777-787.
166. Ogino S, Shima K, Meyerhardt J, et al. Predictive and prognostic roles of BRAF mutation in stage III colon cancer: results from Intergroup Trial CALGB 89803. Clin Cancer Res 2012;18:890-900.
167. French AJ, Sargent DJ, Burgart LJ, et al. Prognostic significance of defective mismatch repair and BRAF V600E in patients with colon cancer. Clin Cancer Res 2008;14:3408-3415.
168. Samowitz WS, Sweeney C, Herrick J, et al. Poor survival associated with the BRAF V600E mutation in microsatellite-stable colon cancers. Cancer Res 2005;65:6063-6069.
169. Zlobec I, Bihl MP, Schwarb H, et al. Clinicopatholo-gical and protein characterization of BRAF-and K-RAS-mutated colorectal cancer and implications for prognosis. Int J Cancer 2010;127:367-380.
170. Roth AD, Tejpar S, Delorenzi M, et al. Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial. J Clin Oncol 2010;28:466-474.
171. Souglakos J, Philips J, Wang R, et al. Prognostic and predictive value of common mutations for treatment response and survival in patients with metastatic colorectal cancer. Br J Cancer 2009;101: 465-472.
172. Farina-Sarasqueta A, van Lijnschoten G, Moerland E, et al. The BRAF V600E mutation is an independent prognostic factor for survival in stage II and stage III colon cancer patients. Ann Oncol 2010;21: 2396-2402.
173. Ferracin M, Gafa R, Miotto E, et al. The methylator phenotype in microsatellite stable colorectal cancers is characterized by a distinct gene expression profile. J Pathol 2008;214:594-602. (Pubitemid 351482274)
174. Saridaki Z, Papadatos-Pastos D, Tzardi M, et al. BRAF mutations, microsatellite instability status and cyclin D1 expression predict metastatic colorectal patients' outcome. Br J Cancer 2010;102:1762-1768.
175. Kalady MF, Sanchez JA, Manilich E, et al. Divergent oncogenic changes influence survival differences between colon and rectal adenocarcinomas. Dis Colon Rectum 2009;52:1039-1045.
176. Popat S, Hubner R, Houlston RS. Systematic review of microsatellite instability and colorectal cancer prognosis. J Clin Oncol 2005;23:609-618. (Pubitemid 46224239)
177. Richman SD, Seymour MT, Chambers P, et al. KRAS and BRAF mutations in advanced colorectal cancer are associated with poor prognosis but do not preclude benefit from oxaliplatin or irinotecan: results from the MRC FOCUS trial. J Clin Oncol 2009;27:5931-5937.
178. Hutchins G, Southward K, Handley K, et al. Value of mismatch repair, KRAS, and BRAF mutations in predicting recurrence and benefits from chemotherapy in colorectal cancer. J Clin Oncol 2011;29: 1261-1270.
179. Price TJ, Hardingham JE, Lee CK, et al. Impact of KRAS and BRAF gene mutation status on outcomes from the Phase III AGITG MAX trial of capecitabine alone or in combination with bevacizumab and mitomycin in advanced colorectal cancer. J Clin Oncol 2011;29:2675-2682.
180. Phipps AI, Buchanan DD, Makar KW, et al. BRAF mutation status and survival after colorectal cancer diagnosis according to patient and tumor characteristics. Cancer Epidemiol Biomarkers Prev 2012;21: 1792-1798.
181. Gavin P, Colangelo LH, Fumagalli D, et al. Mutation profiling and microsatellite instability in stage II and III colon cancer: an assessment of their prognostic and oxaliplatin predictive value. Clin Cancer Res 2012;18:6531-6541.
182. Popovici V, Budinska E, Tejpar S, et al. Identification of a poor-prognosis BRAF-mutant-like population of patients with colon cancer. J Clin Oncol 2012;30:1288-1295.
183. Nosho K, Kure S, Irahara N, et al. A prospective cohort study shows unique epigenetic, genetic, and prognostic features of synchronous colorectal cancers. Gastroenterology 2009;137:1609-1620.e1603.
184. Konishi K, Shen L, Jelinek J, et al. Concordant DNA methylation in synchronous colorectal carcinomas. Cancer Prev Res (Philadelphia, PA) 2009;2: 814-822.
185. Gonzalo V, Lozano JJ, Munoz J, et al. Aberrant gene promoter methylation associated with sporadic multiple colorectal cancer. PLoS One 2010;5:e8777.
186. Leggett BA, Worthley DL. Synchronous colorectal cancer: not just bad luck? Gastroenterology 2009; 137:1559-1562.
187. Funkhouser WK, Lubin IM, Monzon FA, et al. Relevance, pathogenesis, and testing algorithm for mismatch repair-defective colorectal carcinomas: a report of the Association for Molecular Pathology. J Mol Diagn 2012;14:91-103.
188. Tournier B, Chapusot C, Courcet E, et al. Why do results conflict regarding the prognostic value of the methylation status in colon cancers? The role of the preservation method. BMC Cancer 2012;12:12.
189. Ang PW, Loh M, Liem N, et al. Comprehensive profiling of DNA methylation in colorectal cancer reveals subgroups with distinct clinicopathological and molecular features. BMC Cancer 2010;10:227.
190. Rawson JB, Bapat B. Epigenetic biomarkers in color-ectal cancer diagnostics. Expert Rev Mol Diagn 2012;12:499-509.
191. Morikawa T, Shima K, Kuchiba A, et al. No evidence for interference of h&e staining in DNA testing: usefulness of DNA extraction from h&e-stained archival tissue sections. Am J Clin Pathol 2012;138: 122-129.
192. Ogino S, Kawasaki T, Brahmandam M, et al. Sensitive sequencing method for KRAS mutation detection by pyrosequencing. J Mol Diagn 2005;7:413-421. (Pubitemid 41149657)
193. Ogino S, Kawasaki T, Brahmandam M, et al. Precision and performance characteristics of bisulfite conversion and real-time PCR (MethyLight) for quantitative DNA methylation analysis. J Mol Diagn 2006;8: 209-217. (Pubitemid 43811244)
194. Irahara N, Nosho K, Baba Y, et al. Precision of pyrosequencing assay to measure LINE-1 methylation in colon cancer, normal colonic mucosa and peripheral blood cells. J Mol Diagn 2010;12:177-183.
195. Ogino S, Kawasaki T, Kirkner GJ, et al. Evaluation of markers for CpG island methylator phenotype (CIMP) in colorectal cancer by a large population-based sample. J Mol Diagn 2007;9:305-314. (Pubitemid 47305066)
196. Rosenberg AR, Skapek SX, Hawkins DS. The inconvenience of convenience cohorts: rhabdomyosarcoma and the PAX-FOXO1 biomarker. Cancer Epidemiol Biomarkers Prev 2012;21:1012-1018.
197. Ioannidis JP. Why most published research findings are false. PLoS Med 2005;2:e124.
198. Kitkumthorn N, Mutirangura A. Long interspersed nuclear element-1 hypomethylation in cancer: biology and clinical applications. Clin Epigenet 2012;2: 315-330.
199. Yang AS, Estecio MR, Doshi K, et al. A simple method for estimating global DNA methylation using bisulfite PCR of repetitive DNA elements. Nucleic Acids Res 2004;32:e38.
200. Frigola J, Sole X, Paz MF, et al. Differential DNA hypermethylation and hypomethylation signatures in colorectal cancer. Hum Mol Genet 2005;14:319-326.
201. Aporntewan C, Phokaew C, Piriyapongsa J, et al. Hypomethylation of intragenic LINE-1 represses transcription in cancer cells through AGO2. PLoS One 2011;6:e17934.
202. Wissing S, Munoz-Lopez M, Macia A, et al. Repro-gramming somatic cells into iPS cells activates LINE-1 retroelement mobility. Hum Mol Genet 2012; 21:208-218.
203. Speek M. Antisense promoter of human L1 retro-transposon drives transcription of adjacent cellular genes. Mol Cell Biol 2001;21:1973-1985. (Pubitemid 32479621)
204. Peaston AE, Evsikov AV, Graber JH, et al. Retro-transposons regulate host genes in mouse oocytes and preimplantation embryos. Dev Cell 2004;7:597-606. (Pubitemid 39341844)
205. Faulkner GJ, Kimura Y, Daub CO, et al. The regulated retrotransposon transcriptome of mammalian cells. Nat Genet 2009;41:563-571.
206. Han JS, Szak ST, Boeke JD. Transcriptional disruption by the L1 retrotransposon and implications for mammalian transcriptomes. Nature 2004;429:268-274. (Pubitemid 38684807)
207. Yamada Y, Jackson-Grusby L, Linhart H, et al. Opposing effects of DNA hypomethylation on intestinal and liver carcinogenesis. Proc Natl Acad Sci USA 2005;102:13580-13585. (Pubitemid 41420891)
208. Howard G, Eiges R, Gaudet F, et al. Activation and transposition of endogenous retroviral elements in hypomethylation induced tumors in mice. Oncogene 2008;27:404-408.
209. Estecio MR, Gharibyan V, Shen L, et al. LINE-1 hypomethylation in cancer is highly variable and inversely correlated with microsatellite instability. PLoS One 2007;2:e399.
210. Baba Y, Huttenhower C, Nosho K, et al. Epigenomic diversity of colorectal cancer indicated by LINE-1 methylation in a database of 869 tumors. Mol Cancer 2010;9:125.
211. Bae JM, Shin S, Kwon H, et al. ALU and LINE-1 hypomethylations in multistep gastric carcinogenesis and their prognostic implications. Int J Cancer 2012;131:1323-1331.
212. Igarashi S, Suzuki H, Niinuma T, et al. A novel correlation between LINE-1 hypomethylation and the malignancy of gastrointestinal stromal tumors. Clin Cancer Res 2010;16:5114-5123.
213. Pattamadilok J, Huapai N, Rattanatanyong P, et al. LINE-1 hypomethylation level as a potential prognostic factor for epithelial ovarian cancer. Int J Gynecol Cancer 2008;18:711-717. (Pubitemid 352020191)
214. Roman-Gomez J, Jimenez-Velasco A, Agirre X, et al. Promoter hypomethylation of the LINE-1 retrotran-sposable elements activates sense/antisense transcription and marks the progression of chronic myeloid leukemia. Oncogene 2005;24:7213-7223. (Pubitemid 41679283)
215. Hoshimoto S, Kuo CT, Chong KK, et al. AIM1 and LINE-1 epigenetic aberrations in tumor and serum relate to melanoma progression and disease outcome. J Invest Dermatol 2012;132:1689-1697.
216. Ogino S, Nosho K, Kirkner GJ, et al. A cohort study of tumoral LINE-1 hypomethylation and prognosis in colon cancer. J Natl Cancer Inst 2008;100: 1734-1738.
217. Ahn JB, Chung WB, Maeda O, et al. DNA methylation predicts recurrence from resected stage III proximal colon cancer. Cancer 2011;117:1847-1854.
218. Rhee YY, Kim MJ, Bae JM, et al. Clinical outcomes of patients with microsatellite-unstable colorectal carcinomas depend on L1 methylation level. Ann Surg Oncol 2012;19:3441-3448.
219. Yegnasubramanian S, Haffner MC, Zhang Y, et al. DNA hypomethylation arises later in prostate cancer progression than CpG island hypermethylation and contributes to metastatic tumor heterogeneity. Cancer Res 2008;68:8954-8967.
220. Choi IS, Estecio MR, Nagano Y, et al. Hypomethyla-tion of LINE-1 and Alu in well-differentiated neu-roendocrine tumors (pancreatic endocrine tumors and carcinoid tumors). Mod Pathol 2007;20:802-810. (Pubitemid 46933452)
221. Sunami E, de Maat M, Vu A, et al. LINE-1 hypo-methylation during primary colon cancer progression. PLoS One 2011;6:e18884.
222. Ogino S, Nosho K, Irahara N, et al. Prognostic significance and molecular associations of 18q loss of heterozygosity: a cohort study of microsatellite stable colorectal cancers. J Clin Oncol 2009;26: 5713-5720.
223. Lochhead P, Imamura Y, Morikawa T, et al. Insulinlike growth factor 2 messenger RNA binding protein 3 (IGF2BP3) is a marker of unfavourable prognosis in colorectal cancer. Eur J Cancer 2012;48:3405-3413.
224. Baba Y, Nosho K, Shima K, et al. Hypomethylation of the IGF2 DMR in colorectal tumors, detected by bisulfite pyrosequencing, is associated with poor prognosis. Gastroenterology 2010;139:1855-1864.
225. Ito Y, Koessler T, Ibrahim AE, et al. Somatically acquired hypomethylation of IGF2 in breast and col-orectal cancer. Hum Mol Genet 2008;17:2633-2643.
226. Antelo M, Balaguer F, Shia J, et al. A high degree of LINE-1 hypomethylation is a unique feature of early-onset colorectal cancer. PLoS One 2012;7:e45357.
227. Goel A, Xicola RM, Nguyen TP, et al. Aberrant DNA methylation in hereditary nonpolyposis colorectal cancer without mismatch repair deficiency. Gastro-enterology 2010;138:1854-1862.
228. Ogino S, Nishihara R, Lochhead P, et al. Prospective study of family history and colorectal cancer risk by tumor LINE-1 methylation level. J Natl Cancer Inst 2013 (in press).
229. Carmona FJ, Villanueva A, Vidal A, et al. Epigenetic disruption of cadherin-11 in human cancer metastasis. J Pathol 2012;228:230-240.
230. Ogino S, Meyerhardt JA, Irahara N, et al. KRAS mutation in stage III colon cancer and clinical outcome following intergroup trial CALGB 89803. Clin Cancer Res 2009;15:7322-7329.
231. Lievre A, Blons H, Laurent-Puig P. Oncogenic mutations as predictive factors in colorectal cancer. Oncogene 2010;29:3033-3043.
232. Myers MB, Wang Y, McKim KL, et al. Hotspot oncomutations: implications for personalized cancer treatment. Expert Rev Mol Diagn 2012;12:603-620.
233. Voutsina A, Tzardi M, Kalikaki A, et al. Combined analysis of KRAS and PIK3CA mutations, MET and PTEN expression in primary tumors and corresponding metastases in colorectal cancer. Mod Pathol 2012.
234. Bond CE, Umapathy A, Buttenshaw RL, et al. Chromosomal Instability in BRAF mutant, microsa-tellite stable colorectal cancers. PLoS One 2012;7:e47483.
235. Adams MD, Veigl ML, Wang Z, et al. Global mutational profiling of formalin-fixed human colon cancers from a pathology archive. Mod Pathol 2012; 25:1599-1608.
236. Esteller M, Risques RA, Toyota M, et al. Promoter hypermethylation of the DNA repair gene O(6)-methylguanine-DNA methyltransferase is associated with the presence of G:C to A:T transition mutations in p53 in human colorectal tumorigenesis. Cancer Res 2001;61:4689-4692. (Pubitemid 32691877)
237. Esteller M, Toyota M, Sanchez-Cespedes M, et al. Inactivation of the DNA repair gene O6-methylgua-nine-DNA methyltransferase by promoter hyper-methylation is associated with G to A mutations in K-ras in colorectal tumorigenesis. Cancer Res 2000;60:2368-2371. (Pubitemid 30262424)
238. Halford S, Rowan A, Sawyer E, et al. O6-methylgua-nine methyltransferase in colorectal cancers: detection of mutations, loss of expression, and weak association with G:C4A:T transitions. Gut 2005;54:797-802. (Pubitemid 40732096)
239. Nosho K, Kawasaki T, Ohnishi M, et al. PIK3CA mutation in colorectal cancer: relationship with genetic and epigenetic alterations. Neoplasia 2008; 10:534-541. (Pubitemid 351770297)
240. Suehiro Y, Wong CW, Chirieac LR, et al. Epigenetic-genetic interactions in the APC/WNT, RAS/RAF, and P53 pathways in colorectal carcinoma. Clin Cancer Res 2008;14:2560-2569.
241. Shima K, Morikawa T, Baba Y, et al. MGMT promoter methylation, loss of expression and prognosis in 855 colorectal cancers. Cancer Causes Control 2011;22:301-309.
242. de Vogel S, Weijenberg MP, Herman JG, et al. MGMT and MLH1 promoter methylation versus APC, KRAS and BRAF gene mutations in colorectal cancer: indications for distinct pathways and sequence of events. Ann Oncol 2009;20:1216-1222.
243. Timmermann B, Kerick M, Roehr C, et al. Somatic mutation profiles of MSI and MSS colorectal cancer identified by whole exome next generation sequencing and bioinformatics analysis. PLoS One 2010;5:e15661.
244. Shah SN, Hile SE, Eckert KA. Defective mismatch repair, microsatellite mutation bias, and variability in clinical cancer phenotypes. Cancer Res 2010;70: 431-435.
245. Dulak AM, Schumacher S, van Lieshout J, et al. Gastrointestinal adenocarcinomas of the esophagus, stomach and colon exhibit distinct patterns of genome instability and oncogenesis. Cancer Res 2012;72:4383-4393.
246. Donehower LA, Creighton CJ, Schultz N, et al. MLH1-silenced and non-silenced subgroups of hypermu-tated colorectal carcinomas have distinct mutational landscapes. J Pathol 2013;229:99-110.
247. Nosho K, Kawasaki T, Chan AT, et al. Cyclin D1 is frequently overexpressed in microsatellite unstable colorectal cancer, independent of CpG island methy-lator phenotype. Histopathology 2008;53:588-598.
248. Shima K, Nosho K, Baba Y, et al. Prognostic significance of CDKN2A (p16) promoter methylation and loss of expression in 902 colorectal cancers: cohort study and literature review. Int J Cancer 2011;128:1080-1094.
249. Belt EJ, Brosens RP, Delis-van Diemen PM, et al. Cell cycle proteins predict recurrence in stage II and III colon cancer. Ann Surg Oncol 2012;19:S682-S692.
250. Gu H, Bock C, Mikkelsen TS, et al. Genome-scale DNA methylation mapping of clinical samples at single-nucleotide resolution. Nat Methods 2010;7: 133-136.
251. Kibriya MG, Raza M, Jasmine F, et al. A genome-wide DNA methylation study in colorectal carcinoma. BMC Med Genomics 2011;4:50.
252. Jasmine F, Rahaman R, Roy S, et al. Interpretation of genome-wide infinium methylation data from ligated DNA in formalin-fixed, paraffin-embedded paired tumor and normal tissue. BMC Res Notes 2012;5:117.
253. Samowitz WS, Albertsen H, Sweeney C, et al. Association of smoking, CpG island methylator phenotype, and V600E BRAF mutations in colon cancer. J Natl Cancer Inst 2006;98:1731-1738. (Pubitemid 44942711)
254. Curtin K, Samowitz WS, Wolff RK, et al. Somatic alterations, metabolizing genes and smoking in rectal cancer. Int J Cancer 2009;125:158-164.
255. Limsui D, Vierkant RA, Tillmans LS, et al. Cigarette smoking and colorectal cancer risk by molecularly defined subtypes. J Natl Cancer Inst 2010;102: 1012-1022.
256. Nishihara R, Morikawa T, Kuchiba A, et al. A prospective study of duration of smoking cessation and colorectal cancer risk by epigenetics-related tumor classification. Am J Epidemiol 2013 (in press).
257. Poynter JN, Haile RW, Siegmund KD, et al. Associations between smoking, alcohol consumption, and colorectal cancer, overall and by tumor microsatellite instability status. Cancer Epidemiol Biomarkers Prev 2009;18:2745-2750.
258. Lindor NM, Yang P, Evans I, et al. Alpha-1-antitrypsin deficiency and smoking as risk factors for mismatch repair deficient colorectal cancer: A study from the colon cancer family registry. Mol Genet Metab 2010;99:157-159.
259. Eaton AM, Sandler R, Carethers JM, et al. 5, 10-Methylenetetrahydrofolate reductase 677 and 1298 polymorphisms, folate intake, and microsatellite instability in colon cancer. Cancer Epidemiol Bio-markers Prev 2005;14:2023-2029. (Pubitemid 41161218)
260. Chia VM, Newcomb PA, Bigler J, et al. Risk of microsatellite-unstable colorectal cancer is associated jointly with smoking and nonsteroidal anti-inflammatory drug use. Cancer Res 2006;66:6877-6883. (Pubitemid 44101982)
261. Rozek LS, Herron CM, Greenson JK, et al. Smoking, gender, and ethnicity predict somatic BRAF mutations in colorectal cancer. Cancer Epidemiol Biomar-kers Prev 2010;19:838-843.
262. Russo AL, Thiagalingam A, Pan H, et al. Differential DNA hypermethylation of critical genes mediates the stage-specific tobacco smoke-induced neoplastic progression of lung cancer. Clin Cancer Res 2005;11:2466-2470. (Pubitemid 40569441)
263. Vaissiere T, Hung RJ, Zaridze D, et al. Quantitative analysis of DNA methylation profiles in lung cancer identifies aberrant DNA methylation of specific genes and its association with gender and cancer risk factors. Cancer Res 2009;69:243-252.
264. Ulrich CM, Potter JD. Folate and cancer-timing is everything. JAMA 2007;297:2408-2409.
265. Carroll C, Cooper K, Papaioannou D, et al. Meta-analysis: folic acid in the prevention of colorectal adenomas and the chemoprevention of colorectal cancer. Aliment Pharmacol Ther 2010;31:708-718.
266. Cole BF, Baron JA, Sandler RS, et al. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA 2007;297:2351-2359. (Pubitemid 46883748)
267. Kadaveru K, Protiva P, Greenspan EJ, et al. Dietary methyl donor depletion protects against intestinal tumorigenesis in ApcMin/+ mice. Cancer Prev Res (Philadelphia) 2012;5:911-920.
268. Schaible TD, Harris RA, Dowd SE, et al. Maternal methyl-donor supplementation induces prolonged murine offspring colitis susceptibility in association with mucosal epigenetic and microbiomic changes. Hum Mol Genet 2011;20:1687-1696.
269. Kim YI, Pogribny IP, Salomon RN, et al. Exon-specific DNA hypomethylation of the p53 gene of rat colon induced by dimethylhydrazine. Modulation by dietary folate. Am J Pathol 1996;149:1129-1137. (Pubitemid 26337232)
270. Kawakami K, Ruszkiewicz A, Bennett G, et al. The folate pool in colorectal cancers is associated with DNA hypermethylation and with a polymorphism in methylenetetrahydrofolate reductase. Clin Cancer Res 2003;9:5860-5865. (Pubitemid 38018068)
271. van Engeland M, Weijenberg MP, Roemen GM, et al. Effects of dietary folate and alcohol intake on promoter methylation in sporadic colorectal cancer: the Netherlands Cohort Study on diet and cancer. Cancer Res 2003;63:3133-3137. (Pubitemid 36735864)
272. Schernhammer ES, Giovannucci E, Baba Y, et al. B vitamins, methionine and alcohol intake and risk of colon cancer in relation to BRAF mutation and CpG island methylator phenotype (CIMP). PLoS One 2011;6:e21102.
273. Razzak AA, Oxentenko AS, Vierkant RA, et al. Alcohol intake and colorectal cancer risk by molecu-larly defined subtypes in a prospective study of older women. Cancer Prev Res (Philadelphia) 2011;4: 2035-2043.
274. Slattery ML, Curtin K, Sweeney C, et al. Diet and lifestyle factor associations with CpG island methy-lator phenotype and BRAF mutations in colon cancer. Int J Cancer 2007;120:656-663. (Pubitemid 44969038)
275. Curtin K, Samowitz WS, Ulrich CM, et al. Nutrients in folate-mediated, one-carbon metabolism and the risk of rectal tumors in men and women. Nutr Cancer 2011;63:357-366.
276. Curtin K, Ulrich CM, Samowitz WS, et al. Candidate pathway polymorphisms in one-carbon metabolism and risk of rectal tumor mutations. Int J Mol Epidemiol Genet 2011;2:1-8.
277. Razzak AA, Oxentenko AS, Vierkant RA, et al. Associations between intake of folate and related micronutrients with molecularly defined colorectal cancer risks in the Iowa Women's Health Study. Nutr Cancer 2012;64:899-910.
278. de Vogel S, Wouters KA, Gottschalk RW, et al. Genetic variants of methyl metabolizing enzymes and epige-netic regulators: associations with promoter CpG island hypermethylation in colorectal cancer. Cancer Epidemiol Biomarkers Prev 2009;18:3086-3096.
279. Curtin K, Slattery ML, Ulrich CM, et al. Genetic polymorphisms in one-carbon metabolism: associations with CpG island methylator phenotype (CIMP) in colon cancer and the modifying effects of diet. Carcinogenesis 2007;28:1672-1679. (Pubitemid 47303944)
280. Hazra A, Fuchs CS, Kawasaki T, et al. Germline polymorphisms in the one-carbon metabolism pathway and DNA methylation in colorectal cancer. Cancer Causes Control 2010;21:331-345.
281. Linhart HG, Troen A, Bell GW, et al. Folate deficiency induces genomic uracil misincorporation and hypo-methylation but does not increase DNA point mutations. Gastroenterology 2009;136:e223.
282. Hervouet E, Debien E, Campion L, et al. Folate supplementation limits the aggressiveness of glioma via the remethylation of DNA repeats element and genes governing apoptosis and proliferation. Clin Cancer Res 2009;15:3519-3529.
283. Wasson GR, McGlynn AP, McNulty H, et al. Global DNA and p53 region-specific hypomethylation in human colonic cells is induced by folate depletion and reversed by folate supplementation. J Nutr 2006;136:2748-2753. (Pubitemid 44771768)
284. Schernhammer ES, Ogino S, Fuchs CS. Folate intake and risk of colon cancer in relation to p53 status. Gastroenterology 2008;135:770-780.
285. Schernhammer ES, Giovannucci E, Kawasaki T, et al. Dietary folate, alcohol, and B vitamins in relation to LINE-1 hypomethylation in colon cancer. Gut 2010;59:794-799.
286. Figueiredo JC, Grau MV, Wallace K, et al. Global DNA hypomethylation (LINE-1) in the normal colon and lifestyle characteristics and dietary and genetic factors. Cancer Epidemiol Biomarkers Prev 2009; 18:1041-1049.
287. Pufulete M, Al-Ghnaniem R, Khushal A, et al. Effect of folic acid supplementation on genomic DNA methylation in patients with colorectal adenoma. Gut 2005;54:648-653. (Pubitemid 40559249)
288. Vrieling A, Kampman E. The role of body mass index, physical activity, and diet in colorectal cancer recurrence and survival: a review of the literature. Am J Clin Nutr 2010;92:471-490.
289. Ballard-Barbash R, Friedenreich CM, Courneya KS, et al. Physical activity, biomarkers, and disease outcomes in cancer survivors: a systematic review. J Natl Cancer Inst 2012;104:815-840.
290. Jeon JY, Meyerhardt JA. Energy in and energy out: what matters for survivors of colorectal cancer? J Clin Oncol 2012;30:7-10.
291. Giovannucci EL. Physical activity as a standard cancer treatment. J Natl Cancer Inst 2012;104: 797-799.
292. Clague J, Bernstein L. Physical activity and cancer. Curr Oncol Rep 2012;14:550-558.
293. Betof AS, Dewhirst MW, Jones LW. Effects and potential mechanisms of exercise training on cancer progression: a translational perspective. Brain Behav Immun 2013 (in press).
294. Hughes LA, van den Brandt PA, de Bruine AP, et al. Early life exposure to famine and colorectal cancer risk: a role for epigenetic mechanisms. PLoS One 2009;4:e7951.
295. Slattery ML, Curtin K, Anderson K, et al. Associations between cigarette smoking, lifestyle factors, and microsatellite instability in colon tumors. J Natl Cancer Inst 2000;92:1831-1836.
296. Satia JA, Keku T, Galanko JA, et al. Diet, lifestyle, and genomic instability in the North Carolina Colon Cancer Study. Cancer Epidemiol Biomarkers Prev 2005;14:429-436. (Pubitemid 40270108)
297. Campbell PT, Jacobs ET, Ulrich CM, et al. Case-control study of overweight, obesity, and colorectal cancer risk, overall and by tumor microsatellite instability status. J Natl Cancer Inst 2010;102: 391-400.
298. Kuchiba A, Morikawa T, Yamauchi M, et al. Body mass index and risk of colorectal cancer according to fatty acid synthase expression in the Nurses' Health Study. J Natl Cancer Inst 2012;104:415-420.
299. Uddin S, Hussain AR, Ahmed M, et al. High prevalence of fatty acid synthase expression in colorectal cancers in middle eastern patients and its potential role as a therapeutic target. Am J Gastro-enterol 2009;104:1790-1801.
300. Migita T, Ruiz S, Fornari A, et al. Fatty acid synthase: a metabolic enzyme and candidate oncogene in prostate cancer. J Natl Cancer Inst 2009;101: 519-532.
301. Ogino S, Kawasaki T, Ogawa A, et al. Fatty acid synthase overexpression in colorectal cancer is associated with microsatellite instability, independent of CpG island methylator phenotype. Hum Pathol 2007;38:842-849. (Pubitemid 46726510)
302. Baba Y, Nosho K, Shima K, et al. Prognostic significance of AMP-activated protein kinase expression and modifying effect of MAPK3/1 in colorectal cancer. Br J Cancer 2010;103:1025-1033.
303. Ogino S, Nosho K, Baba Y, et al. A cohort study of STMN1 expression in colorectal cancer: body mass index and prognosis. Am J Gastroenterol 2009;104: 2047-2056.
304. Ogino S, Nosho K, Shima K, et al. P21 expression in colon cancer and modifying effects of patient age and body mass index on prognosis. Cancer Epidemiol Biomarkers Prev 2009;18:2513-2521.
305. Ogino S, Shima K, Nosho K, et al. A cohort study of p27 localization in colon cancer, body mass index, and patient survival. Cancer Epidemiol Biomarkers Prev 2009;18:1849-1858.
306. Meyerhardt JA, Ogino S, Kirkner GJ, et al. Interaction of molecular markers and physical activity on mortality in patients with colon cancer. Clin Cancer Res 2009;15:5931-5936.
307. Li L, Lee KM, Han W, et al. Estrogen and progesterone receptor status affect genome-wide DNA methylation profile in breast cancer. Hum Mol Genet 2010;19: 4273-4277.
308. Wu AH, Siegmund KD, Long TI, et al. Hormone therapy, DNA methlyation and colon cancer. Carci-nogenesis 2010;31:1060-1067.
309. Lin JH, Morikawa T, Chan AT, et al. Postmenopausal hormone therapy is associated with a reduced risk of colorectal cancer lacking CDKN1A expression. Cancer Res 2012;72:3020-3028.
310. Kure S, Nosho K, Baba Y, et al. Vitamin D receptor expression is associated with PIK3CA and KRAS mutations in colorectal cancer. Cancer Epidemiol Biomarkers Prev 2009;18:2765-2772.
311. Pereira F, Barbachano A, Silva J, et al. KDM6B/JMJD3 histone demethylase is induced by vitamin D and modulates its effects in colon cancer cells. Hum Mol Genet 2011;20:4655-4665.
312. Blumberg R, F Powrie. Microbiota disease, and back to health: a metastable journey. Sci Transl Med 2012;4:137rv137.
313. Larsson E, Tremaroli V, Lee YS, et al. Analysis of gut microbial regulation of host gene expression along the length of the gut and regulation of gut microbial ecology through MyD88. Gut 2012;61:1124-1131.
314. Ly NP, Litonjua A, Gold DR, et al. Gut microbiota, probiotics, and vitamin D: interrelated exposures influencing allergy, asthma, and obesity? J Allergy Clin Immunol 2011;127:1087-1094; quiz 1095-1086.
315. Allen M, Louise JJ. Jekyll and Hyde: the role of the microenvironment on the progression of cancer. J Pathol 2011;223:162-176.
316. Fridman WH, Pages F, Sautes-Fridman C, et al. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer 2012;12:298-306.
317. Ding SZ, Goldberg JB, Hatakeyama M. Helicobacter pylori infection, oncogenic pathways and epigenetic mechanisms in gastric carcinogenesis. Fut Oncol 2010;6:851-862.
318. Peterson AJ, Menheniott TR, O'Connor L, et al. Helicobacter pylori infection promotes methylation and silencing of trefoil factor 2, leading to gastric tumor development in mice and humans. Gastroen-terology 2010;139:2005-2017.
319. Bebek G, Bennett KL, Funchain P, et al. Microbiomic subprofiles and MDR1 promoter methylation in head and neck squamous cell carcinoma. Hum Mol Genet 2012;21:1557-1565.
320. Fernandez AF, Esteller M. Viral epigenomes in human tumorigenesis. Oncogene 2010;29:1405-1420.
321. Fernandez AF, Rosales C, Lopez-Nieva P, et al. The dynamic DNA methylomes of double-stranded DNA viruses associated with human cancer. Genome Res 2009;19:438-451.
322. De-Castro Arce J, Gockel-Krzikalla E, Rosl F. Silencing of multi-copy HPV16 by viral self-methylation and chromatin occlusion: a model for epigenetic virus-host interaction. Hum Mol Genet 2012;21: 1693-1705.
323. Hino R, Uozaki H, Murakami N, et al. Activation of DNA methyltransferase 1 by EBV latent membrane protein 2A leads to promoter hypermethylation of PTEN gene in gastric carcinoma. Cancer Res 2009; 69:2766-2774.
324. Goel A, Li MS, Nagasaka T, et al. Association of JC virus T-antigen expression with the methylator phenotype in sporadic colorectal cancers. Gastroen-terology 2006;130:1950-1961. (Pubitemid 43816967)
325. Nosho K, Shima K, Kure S, et al. JC virus T-antigen in colorectal cancer is associated with p53 expression and chromosomal instability, independent of CpG island methylator phenotype. Neoplasia 2009;11: 87-95.
326. Karpinski P, Myszka A, Ramsey D, et al. Detection of viral DNA sequences in sporadic colorectal cancers in relation to CpG island methylation and methylator phenotype. Tumour Biol 2011;32:653-659.
327. Wang D, Dubois RN. The role of COX-2 in intestinal inflammation and colorectal cancer. Oncogene 2010; 29:781-788.
328. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 2010;140:883-899.
329. Wang D, Xia D, DuBois RN. The crosstalk of PTGS2 and EGF signaling pathways in colorectal cancer. Cancers 2011;3:3894-3908.
330. Wang D, Dubois RN. Associations between obesity and cancer: the role of fatty acid synthase. J Natl Cancer Inst 2012;104:343-345.
331. Girnun G. PPARG: a new independent marker for colorectal cancer survival. Gastroenterology 2009; 136:1157-1160.
332. Kanai Y, Hirohashi S. Alterations of DNA methylation associated with abnormalities of DNA methyltrans-ferases in human cancers during transition from a precancerous to a malignant state. Carcinogenesis 2007;28:2434-2442. (Pubitemid 350238944)
333. O'Hagan HM, Wang W, Sen S, et al. Oxidative damage targets complexes containing DNA methyltrans-ferases, SIRT1, and polycomb members to promoter CpG islands. Cancer Cell 2011;20:606-619.
334. Brigati C, Banelli B, di Vinci A, et al. Inflammation, HIF-1, and the epigenetics that follows. Mediators Inflamm 2010;2010:263914.
335. Xia D, Wang D, Kim SH, et al. Prostaglandin E(2) promotes intestinal tumor growth via DNA methyla-tion. Nat Med 2012;18:224-226.
336. Kellermayer R, Balasa A, Zhang W, et al. Epigenetic maturation in colonic mucosa continues beyond infancy in mice. Hum Mol Genet 2010;19:2168-2176.
337. Chan AT, Ogino S, Fuchs CS. Aspirin and the risk of colorectal cancer in relation to the expression of COX-2. N Engl J Med 2007;356:2131-2142. (Pubitemid 47010839)
338. Ogino S, Kirkner GJ, Nosho K, et al. Cyclooxygenase-2 expression is an independent predictor of poor prognosis in colon cancer. Clin Cancer Res 2008; 14:8221-8227.
339. Yamauchi M, Lochhead P, Morikawa T, et al. Color-ectal cancer: a tale of two sides or a continuum? Gut 2012;61:794-797.
340. Li X, Leblanc J, Truong A, et al. A metaproteomic approach to study human-microbial ecosystems at the mucosal luminal interface. PLoS One 2011;6: e26542.
341. Edin S, Wikberg ML, Dahlin AM, et al. The distribution of macrophages
342. Cortese R, Kwan A, Lalonde E, et al. Epigenetic markers of prostate cancer in plasma circulating DNA. Hum Mol Genet 2012;21:3619-3631.
343. Bollati V, Baccarelli A, Hou L, et al. Changes in DNA methylation patterns in subjects exposed to low-dose benzene. Cancer Res 2007;67:876-880.
344. Terry MB, Delgado-Cruzata L, Vin-Raviv N, et al. DNA methylation in white blood cells: association with risk factors in epidemiologic studies. Epigenetics 2011;6:828-837.
345. Mirabello L, Savage SA, Korde L, et al. LINE-1 methylation is inherited in familial testicular cancer kindreds. BMC Med Genet 2010;11:77.
346. Wu HC, Delgado-Cruzata L, Flom JD, et al. Global methylation profiles in DNA from different blood cell types. Epigenetics 2011;6:76-85.
347. Wu HC, John EM, Ferris JS, et al. Global DNA methylation levels in girls with and without a family history of breast cancer. Epigenetics 2011;6:29-33.
348. Breitling LP, Yang R, Korn B, et al. Tobacco-smoking-related differential DNA methylation: 27K discovery and replication. Am J Hum Genet 2011;88:450-457.
349. van Bemmel D, Lenz P, Liao LM, et al. Correlation of LINE-1 methylation levels in patient-matched buffy coat, serum, buccal cell, and bladder tumor tissue DNA samples. Cancer Epidemiol Biomarkers Prev 2012;21:1143-1148.
350. Breton CV, Byun HM, Wenten M, et al. Prenatal tobacco smoke exposure affects global and gene-specific DNA methylation. Am J Respir Crit Care Med 2009;180:462-467.
351. Breton CV, Salam MT, Wang X, et al. Particulate matter, DNA methylation in nitric oxide synthase, and childhood respiratory disease. Environ Health Perspect 2012;120:1320-1326.
352. Iacopetta B, Grieu F, Phillips M, et al. Methylation levels of LINE-1 repeats and CpG island loci are inversely related in normal colonic mucosa. Cancer Sci 2007;98:1454-1460. (Pubitemid 47241770)
353. Liu J, Hesson LB, Meagher AP, et al. Relative distribution of folate species is associated with global DNA methylation in human colorectal mucosa. Cancer Prev Res (Philadelphia) 2012;5:921-929.
354. Buda A, De Bona M, Dotti I, et al. Prevalence of different subtypes of serrated polyps and risk of synchronous advanced colorectal neoplasia in average-risk population undergoing first-time colono-scopy. Clin Transl Gasntroenterol 2012;3:e6.
355. Hunter DJ. Lessons from genome-wide association studies for epidemiology. Epidemiology 2012;23: 363-367.
356. Spain SL, Carvajal-Carmona LG, Howarth KM, et al. Refinement of the associations between risk of color-ectal cancer and polymorphisms on chromosomes 1q41 and 12q13.13. Hum Mol Genet 2012;21: 934-946.
357. Price AL, Zaitlen NA, Reich D, et al. New approaches to population stratification in genome-wide association studies. Nat Rev Genet 2010;11:459-463.
358. Thomas D. Gene-environment-wide association studies: emerging approaches. Nat Rev Genet 2010;11:259-272.
359. Hutter CM, Chang-Claude J, Slattery ML, et al. Characterization of gene-environment interactions for colorectal cancer susceptibility loci. Cancer Res 2012;72:2036-2044.
360. On beyond GWAS. Nat Genet 2010;42:551.
361. Ghosh A, Hartge P, Purdue MP, et al. Assessing disease risk in genome-wide association studies using family history. Epidemiology 2012;23:616-622.
362. Freedman ML, Monteiro AN, Gayther SA, et al. Principles for the post-GWAS functional characterization of cancer risk loci. Nat Genet 2011;43: 513-518.
363. Tuupanen S, Turunen M, Lehtonen R, et al. The common colorectal cancer predisposition SNP rs6983267 at chromosome 8q24 confers potential to enhanced Wnt signaling. Nat Genet 2009;41:885-890.
364. Gruber SB, Moreno V, Rozek LS, et al. Genetic variation in 8q24 associated with risk of colorectal cancer. Cancer Biol Ther 2007;6:1143-1147. (Pubitemid 351574969)
365. Slattery ML, Herrick J, Curtin K, et al. Increased risk of colon cancer associated with a genetic polymorphism of SMAD7. Cancer Res 2010;70:1479-1485.
366. Garcia-Albeniz X, Nan H, Valeri L, et al. Phenotypic and tumor molecular characterization of colorectal cancer in relation to a susceptibility SMAD7 variant associated with survival. Carcinogenesis 2013 (in press).
367. Rakyan VK, Down TA, Balding DJ, et al. Epigenome-wide association studies for common human diseases. Nat Rev Genet 2011;12:529-541.
368. Heijmans BT, Mill J. Commentary: the seven plagues of epigenetic epidemiology. Int J Epidemiol 2012;41: 74-78.
369. Febbo PG, Ladanyi M, Aldape KD, et al. NCCN Task Force report: evaluating the clinical utility of tumor markers in oncology. J Natl Compr Canc Netw 2011;9((Suppl 5)):S1-S32; quiz S33.
370. Khoury MJ, Gwinn M, Ioannidis JP. The emergence of translational epidemiology: from scientific discovery to population health impact. Am J Epidemiol 2010; 172:517-524.
371. Butler D. Translational research: crossing the valley of death. Nature 2008;453:840-842. (Pubitemid 351832542)
372. Colditz GA, Winn DM. Criteria for the evaluation of large cohort studies: an application to the nurses' health study. J Natl Cancer Inst 2008;100:918-925. (Pubitemid 351957517)
373. Colditz GA, Hankinson SE. The Nurses' Health Study: lifestyle and health among women. Nat Rev Cancer 2005;5:388-396. (Pubitemid 40637830)
374. Robison LL, Armstrong GT, Boice JD, et al. The Childhood Cancer Survivor Study: A National Cancer Institute-supported resource for outcome and intervention research. J Clin Oncol 2009;27: 2308-2318.
375. Colditz GA. Ensuring long-term sustainability of existing cohorts remains the highest priority to inform cancer prevention and control. Cancer Causes Control 2010;21:649-656.
376. Hansen KD, Timp W, Bravo HC, et al. Increased methylation variation in epigenetic domains across cancer types. Nat Genet 2011;43:768-775.
377. Berman BP, Weisenberger DJ, Aman JF, et al. Regions of focal DNA hypermethylation and long-range hypomethylation in colorectal cancer coincide with nuclear lamina-associated domains. Nat Genet 2012;44:40-46.
378. Xu Y, Hu B, Choi AJ, et al. Unique DNA methylome profiles in CpG island methylator phenotype colon cancers. Genome Res 2012;22:283-291.
379. Spitz MR, Caporaso NE, Sellers TA. Integrative cancer epidemiology-the next generation. Cancer Discovery 2012;2:1087-1090.