Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2019

Open Access 01-12-2019 | Colorectal Cancer | Research article

Global differences in the prevalence of the CpG island methylator phenotype of colorectal cancer

Authors: Shailesh Mahesh Advani, Pragati Shailesh Advani, Derek W. Brown, Stacia M. DeSantis, Krittiya Korphaisarn, Helena M. VonVille, Jan Bressler, David S. Lopez, Jennifer S. Davis, Carrie R. Daniel, Amir Mehrvarz Sarshekeh, Dejana Braithwaite, Michael D. Swartz, Scott Kopetz

Published in: BMC Cancer | Issue 1/2019

Login to get access

Abstract

Background

CpG Island Methylator Phenotype (CIMP) is an epigenetic phenotype in CRC characterized by hypermethylation of CpG islands in promoter regions of tumor suppressor genes, leading to their transcriptional silencing and loss of function. While the prevalence of CRC differs across geographical regions, no studies have compared prevalence of CIMP-High phenotype across regions. The purpose of this project was to compare the prevalence of CIMP across geographical regions after adjusting for variations in methodologies to measure CIMP in a meta-analysis.

Methods

We searched PubMed, Medline, and Embase for articles focusing on CIMP published from 2000 to 2018. Two reviewers independently identified 111 articles to be included in final meta-analysis. We classified methods used to quantify CIMP into 4 categories: a) Classical (MINT marker) Panel group b) Weisenberg-Ogino (W-O) group c) Human Methylation Arrays group and d) Miscellaneous group. We compared the prevalence of CIMP across geographical regions after correcting for methodological variations using meta-regression techniques.

Results

The pooled prevalence of CIMP-High across all studies was 22% (95% confidence interval:21–24%; I2 = 94.75%). Pooled prevalence of CIMP-H across Asia, Australia, Europe, North America and South America was 22, 21, 21, 27 and 25%, respectively. Meta-regression analysis identified no significant differences in the prevalence of CIMP-H across geographical regions after correction for methodological variations. In exploratory analysis, we observed variations in CIMP-H prevalence across countries.

Conclusion

Although no differences were found for CIMP-H prevalence across countries, further studies are needed to compare the influence of demographic, lifestyle and environmental factors in relation to the prevalence of CIMP across geographical regions.
Appendix
Available only for authorised users
Literature
1.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394.CrossRefPubMed
2.
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–E86.CrossRefPubMed
3.
4.
Zong L, Abe M, Ji J, Zhu WG, Yu D. Tracking the correlation between CpG island methylator phenotype and other molecular features and clinicopathological features in human colorectal cancers: a systematic review and meta-analysis. Clin Transl Gastroenterol. 2016;7:e151.CrossRefPubMedPubMedCentral
5.
Deschoolmeester V, Baay M, Specenier P, Lardon F, Vermorken JB. A review of the most promising biomarkers in colorectal cancer: one step closer to targeted therapy. Oncologist. 2010;15(7):699–731.CrossRefPubMedPubMedCentral
6.
Toyota M, Ahuja N, Ohe-Toyota M, Herman JG, Baylin SB, Issa JP. CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci U S A. 1999;96(15):8681–6.CrossRefPubMedPubMedCentral
7.
Noffsinger AE. Serrated polyps and colorectal cancer: new pathway to malignancy. Annu Rev Pathol. 2009;4:343–64.CrossRefPubMed
8.
Juo YY, Johnston FM, Zhang DY, Juo HH, Wang H, Pappou EP, et al. Prognostic value of CpG island methylator phenotype among colorectal cancer patients: a systematic review and meta-analysis. Ann Oncol. 2014;25(12):2314–27.CrossRefPubMedPubMedCentral
9.
Hughes LA, Khalid-de Bakker CA, Smits KM, van den Brandt PA, Jonkers D, Ahuja N, et al. The CpG island methylator phenotype in colorectal cancer: progress and problems. Biochim Biophys Acta. 2012;1825(1):77–85.PubMed
10.
Jia M, Gao X, Zhang Y, Hoffmeister M, Brenner H. Different definitions of CpG island methylator phenotype and outcomes of colorectal cancer: a systematic review. Clin Epigenetics. 2016;8:25.CrossRefPubMedPubMedCentral
11.
Weisenberger DJ, Siegmund KD, Campan M, Young J, Long TI, Faasse MA, et al. CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet. 2006;38(7):787–93.CrossRefPubMed
12.
Ogino S, Kawasaki T, Kirkner GJ, Kraft P, Loda M, Fuchs CS. Evaluation of markers for CpG island methylator phenotype (CIMP) in colorectal cancer by a large population-based sample. J Mol Diagn. 2007;9(3):305–14.CrossRefPubMedPubMedCentral
13.
Hinoue T, Weisenberger DJ, Lange CP, Shen H, Byun HM, Van Den Berg D, et al. Genome-scale analysis of aberrant DNA methylation in colorectal cancer. Genome Res. 2012;22(2):271–82.CrossRefPubMedPubMedCentral
14.
Ahn JB, Chung WB, Maeda O, Shin SJ, Kim HS, Chung HC, et al. DNA methylation predicts recurrence from resected stage III proximal colon cancer. Cancer. 2011;117(9):1847–54.CrossRefPubMed
15.
Advani SM, Advani P, DeSantis SM, Brown D, VonVille HM, Lam M, et al. Clinical, pathological, and molecular characteristics of CpG island methylator phenotype in colorectal cancer: a systematic review and meta-analysis. Transl Oncol. 2018;11(5):1188.CrossRefPubMedPubMedCentral
16.
VonVille H. Excel workbooks for systematic reviews; 2015.
17.
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535.CrossRefPubMedPubMedCentral
18.
19.
NCI. Comprehensive molecular characterization of human colon and rectal cancer. Nature. 2012;487(7407):330–7.CrossRef
20.
Borenstein M, Hedges LV, Higgins JP, Rothstein HR. A basic introduction to fixed-effect and random-effects models for meta-analysis. Res Synth Methods. 2010;1(2):97–111.CrossRefPubMed
21.
Thompson SG, Higgins J. How should meta-regression analyses be undertaken and interpreted? Stat Med. 2002;21(11):1559–73.CrossRefPubMed
22.
23.
Sterne JA, Gavaghan D, Egger M. Publication and related bias in meta-analysis: power of statistical tests and prevalence in the literature. J Clin Epidemiol. 2000;53(11):1119–29.CrossRefPubMed
24.
Sterne JA, Egger M. Funnel plots for detecting bias in meta-analysis: guidelines on choice of axis. J Clin Epidemiol. 2001;54(10):1046–55.CrossRefPubMed
25.
Guinney J, Dienstmann R, Wang X, de Reynies A, Schlicker A, Soneson C, et al. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015;21(11):1350–6.CrossRefPubMedPubMedCentral
26.
Kim JH, Cho NY, Bae JM, Kim KJ, Rhee YY, Lee HS, et al. Nuclear maspin expression correlates with the CpG island methylator phenotype and tumor aggressiveness in colorectal cancer. Int J Clin Exp Pathol. 2015;8(2):1920–8.PubMedPubMedCentral
27.
Laskar RS, Ghosh SK, Talukdar FR. Rectal cancer profiling identifies distinct subtypes in India based on age at onset, genetic, epigenetic and clinicopathological characteristics. Mol Carcinog. 2015;54(12):1786–95.CrossRefPubMed
28.
Berg M, Nordgaard O, Korner H, Oltedal S, Smaaland R, Soreide JA, et al. Molecular subtypes in stage II-III colon cancer defined by genomic instability: early recurrence-risk associated with a high copy-number variation and loss of RUNX3 and CDKN2A. PLoS One. 2015;10(4):e0122391.CrossRefPubMedPubMedCentral
29.
Weisenberger DJ, Levine AJ, Long TI, Buchanan DD, Walters R, Clendenning M, et al. Association of the colorectal CpG island methylator phenotype with molecular features, risk factors, and family history. Cancer Epidemiol Biomark Prev. 2015;24(3):512–9.CrossRef
30.
Jorissen RN, Christie M, Mouradov D, Sakthianandeswaren A, Li S, Love C, et al. Wild-type APC predicts poor prognosis in microsatellite-stable proximal colon cancer. Br J Cancer. 2015;113(6):979–88.CrossRefPubMedPubMedCentral
31.
Laskar RS, Talukdar FR, Choudhury JH, Singh SA, Kundu S, Dhar B, et al. Association of HPV with genetic and epigenetic alterations in colorectal adenocarcinoma from Indian population. Tumour Biol. 2015;36(6):4661–70.CrossRefPubMed
32.
Siraj AK, Prabhakaran S, Bavi P, Bu R, Beg S, Hazmi MA, et al. Prevalence of lynch syndrome in a middle eastern population with colorectal cancer. Cancer. 2015;121(11):1762–71.CrossRefPubMed
33.
Renaud F, Vincent A, Mariette C, Crepin M, Stechly L, Truant S, et al. MUC5AC hypomethylation is a predictor of microsatellite instability independently of clinical factors associated with colorectal cancer. Int J Cancer. 2015;136(12):2811–21.CrossRefPubMed
34.
Nosho K, Igarashi H, Ito M, Mitsuhashi K, Kurihara H, Kanno S, et al. Clinicopathological and molecular characteristics of serrated lesions in Japanese elderly patients. Digestion. 2015;91(1):57–63.CrossRefPubMed
35.
Kloten V, Rose M, Kaspar S, von Stillfried S, Knuchel R, Dahl E. Epigenetic inactivation of the novel candidate tumor suppressor gene ITIH5 in colon cancer predicts unfavorable overall survival in the CpG island methylator phenotype. Epigenetics. 2014;9(9):1290–301.CrossRefPubMedPubMedCentral
36.
Shiovitz S, Bertagnolli MM, Renfro LA, Nam E, Foster NR, Dzieciatkowski S, et al. CpG island methylator phenotype is associated with response to adjuvant irinotecan-based therapy for stage III colon cancer. Gastroenterology. 2014;147(3):637–45.CrossRefPubMed
37.
Siraj AK, Bu R, Prabhakaran S, Bavi P, Beg S, Al Hazmi M, et al. A very low incidence of BRAF mutations in middle eastern colorectal carcinoma. Mol Cancer. 2014;13:168.CrossRefPubMedPubMedCentral
38.
Luo Y, Wong CJ, Kaz AM, Dzieciatkowski S, Carter KT, Morris SM, et al. Differences in DNA methylation signatures reveal multiple pathways of progression from adenoma to colorectal cancer. Gastroenterology. 2014;147(2):418–29 e8.CrossRefPubMed
39.
Cleven AH, Derks S, Draht MX, Smits KM, Melotte V, Van Neste L, et al. CHFR promoter methylation indicates poor prognosis in stage II microsatellite stable colorectal cancer. Clin Cancer Res. 2014;20(12):3261–71.CrossRefPubMed
40.
Etienne-Grimaldi MC, Mahamat A, Chazal M, Laurent-Puig P, Olschwang S, Gaub MP, et al. Molecular patterns in deficient mismatch repair colorectal tumours: results from a French prospective multicentric biological and genetic study. Br J Cancer. 2014;110(11):2728–37.CrossRefPubMedPubMedCentral
41.
Kohonen-Corish MR, Tseung J, Chan C, Currey N, Dent OF, Clarke S, et al. KRAS mutations and CDKN2A promoter methylation show an interactive adverse effect on survival and predict recurrence of rectal cancer. Int J Cancer. 2014;134(12):2820–8.CrossRefPubMed
42.
Deb S, Xu H, Tuynman J, George J, Yan Y, Li J, et al. RAD21 cohesin overexpression is a prognostic and predictive marker exacerbating poor prognosis in KRAS mutant colorectal carcinomas. Br J Cancer. 2014;110(6):1606–13.CrossRefPubMedPubMedCentral
43.
Dawson H, Galvan JA, Helbling M, Muller DE, Karamitopoulou E, Koelzer VH, et al. Possible role of Cdx2 in the serrated pathway of colorectal cancer characterized by BRAF mutation, high-level CpG Island methylator phenotype and mismatch repair-deficiency. Int J Cancer. 2014;134(10):2342–51.CrossRefPubMed
44.
Tahara T, Yamamoto E, Suzuki H, Maruyama R, Chung W, Garriga J, et al. Fusobacterium in colonic flora and molecular features of colorectal carcinoma. Cancer Res. 2014;74(5):1311–8.CrossRefPubMedPubMedCentral
45.
Tahara T, Yamamoto E, Madireddi P, Suzuki H, Maruyama R, Chung W, et al. Colorectal carcinomas with CpG island methylator phenotype 1 frequently contain mutations in chromatin regulators. Gastroenterology. 2014;146(2):530–38 e5.CrossRefPubMed
46.
Perea J, Rueda D, Canal A, Rodriguez Y, Alvaro E, Osorio I, et al. Age at onset should be a major criterion for subclassification of colorectal cancer. J Mol Diagn. 2014;16(1):116–26.CrossRefPubMed
47.
Pancione M, Remo A, Zanella C, Sabatino L, Di Blasi A, Laudanna C, et al. The chromatin remodelling component SMARCB1/INI1 influences the metastatic behavior of colorectal cancer through a gene signature mapping to chromosome 22. J Transl Med. 2013;11:297.CrossRefPubMedPubMedCentral
48.
Walsh MD, Clendenning M, Williamson E, Pearson SA, Walters RJ, Nagler B, et al. Expression of MUC2, MUC5AC, MUC5B, and MUC6 mucins in colorectal cancers and their association with the CpG island methylator phenotype. Mod Pathol. 2013;26(12):1642–56.CrossRefPubMed
49.
Al-Temaimi RA, Jacob S, Al-Ali W, Thomas DA, Al-Mulla F. Reduced FHIT expression is associated with mismatch repair deficient and high CpG island methylator phenotype colorectal cancer. J Histochem Cytochem. 2013;61(9):627–38.CrossRefPubMedPubMedCentral
50.
Day FL, Jorissen RN, Lipton L, Mouradov D, Sakthianandeswaren A, Christie M, et al. PIK3CA and PTEN gene and exon mutation-specific clinicopathologic and molecular associations in colorectal cancer. Clin Cancer Res. 2013;19(12):3285–96.CrossRefPubMed
51.
Marisa L, de Reynies A, Duval A, Selves J, Gaub MP, Vescovo L, et al. Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value. PLoS Med. 2013;10(5):e1001453.CrossRefPubMedPubMedCentral
52.
Donada M, Bonin S, Barbazza R, Pettirosso D, Stanta G. Management of stage II colon cancer - the use of molecular biomarkers for adjuvant therapy decision. BMC Gastroenterol. 2013;13:36.CrossRefPubMedPubMedCentral
53.
Oster B, Linnet L, Christensen LL, Thorsen K, Ongen H, Dermitzakis ET, et al. Non-CpG island promoter hypomethylation and miR-149 regulate the expression of SRPX2 in colorectal cancer. Int J Cancer. 2013;132(10):2303–15.CrossRefPubMed
54.
Yang Q, Dong Y, Wu W, Zhu C, Chong H, Lu J, et al. Detection and differential diagnosis of colon cancer by a cumulative analysis of promoter methylation. Nat Commun. 2012;3:1206.CrossRefPubMed
55.
Dallol A, Al-Maghrabi J, Buhmeida A, Gari MA, Chaudhary AG, Schulten HJ, et al. Methylation of the polycomb group target genes is a possible biomarker for favorable prognosis in colorectal cancer. Cancer Epidemiol Biomark Prev. 2012;21(11):2069–75.CrossRef
56.
Zlobec I, Bihl MP, Foerster A, Rufle A, Lugli A. The impact of CpG island methylator phenotype and microsatellite instability on tumour budding in colorectal cancer. Histopathology. 2012;61(5):777–87.CrossRefPubMed
57.
Yamamoto E, Suzuki H, Yamano HO, Maruyama R, Nojima M, Kamimae S, et al. Molecular dissection of premalignant colorectal lesions reveals early onset of the CpG island methylator phenotype. Am J Pathol. 2012;181(5):1847–61.CrossRefPubMed
58.
Kakar S, Deng G, Smyrk TC, Cun L, Sahai V, Kim YS. Loss of heterozygosity, aberrant methylation, BRAF mutation and KRAS mutation in colorectal signet ring cell carcinoma. Mod Pathol. 2012;25(7):1040–7.CrossRefPubMed
59.
Isaksson-Mettavainio M, Palmqvist R, Dahlin AM, Van Guelpen B, Rutegard J, Oberg A, et al. High SMAD4 levels appear in microsatellite instability and hypermethylated colon cancers, and indicate a better prognosis. Int J Cancer. 2012;131(4):779–88.CrossRefPubMed
60.
Whitehall VL, Rickman C, Bond CE, Ramsnes I, Greco SA, Umapathy A, et al. Oncogenic PIK3CA mutations in colorectal cancers and polyps. Int J Cancer. 2012;131(4):813–20.CrossRefPubMed
61.
Jo P, Jung K, Grade M, Conradi LC, Wolff HA, Kitz J, et al. CpG island methylator phenotype infers a poor disease-free survival in locally advanced rectal cancer. Surgery. 2012;151(4):564–70.CrossRefPubMed
62.
Silver A, Sengupta N, Propper D, Wilson P, Hagemann T, Patel A, et al. A distinct DNA methylation profile associated with microsatellite and chromosomal stable sporadic colorectal cancers. Int J Cancer. 2012;130(5):1082–92.CrossRefPubMed
63.
Konishi K, Watanabe Y, Shen L, Guo Y, Castoro RJ, Kondo K, et al. DNA methylation profiles of primary colorectal carcinoma and matched liver metastasis. PLoS One. 2011;6(11):e27889.CrossRefPubMedPubMedCentral
64.
Zlobec I, Bihl M, Foerster A, Rufle A, Lugli A. 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(3):336–43.CrossRefPubMed
65.
Min BH, Bae JM, Lee EJ, Yu HS, Kim YH, Chang DK, et al. The CpG island methylator phenotype may confer a survival benefit in patients with stage II or III colorectal carcinomas receiving fluoropyrimidine-based adjuvant chemotherapy. BMC Cancer. 2011;11:344.CrossRefPubMedPubMedCentral
66.
Bruin SC, He Y, Mikolajewska-Hanclich I, Liefers GJ, Klijn C, Vincent A, et al. Molecular alterations associated with liver metastases development in colorectal cancer patients. Br J Cancer. 2011;105(2):281–7.CrossRefPubMedPubMedCentral
67.
Karpinski P, Myszka A, Ramsey D, Kielan W, Sasiadek MM. Detection of viral DNA sequences in sporadic colorectal cancers in relation to CpG island methylation and methylator phenotype. Tumour Biol. 2011;32(4):653–9.CrossRefPubMed
68.
Jover R, Nguyen TP, Perez-Carbonell L, Zapater P, Paya A, Alenda C, et al. 5-fluorouracil adjuvant chemotherapy does not increase survival in patients with CpG island methylator phenotype colorectal cancer. Gastroenterology. 2011;140(4):1174–81.CrossRefPubMed
69.
Ibrahim AE, Arends MJ, Silva AL, Wyllie AH, Greger L, Ito Y, et al. Sequential DNA methylation changes are associated with DNMT3B overexpression in colorectal neoplastic progression. Gut. 2011;60(4):499–508.CrossRefPubMed
70.
Wong JJ, Hawkins NJ, Ward RL, Hitchins MP. Methylation of the 3p22 region encompassing MLH1 is representative of the CpG island methylator phenotype in colorectal cancer. Mod Pathol. 2011;24(3):396–411.CrossRefPubMed
71.
Limsui D, Vierkant RA, Tillmans LS, Wang AH, Weisenberger DJ, Laird PW, et al. Cigarette smoking and colorectal cancer risk by molecularly defined subtypes. J Natl Cancer Inst. 2010;102(14):1012–22.CrossRefPubMedPubMedCentral
72.
Kim JC, Choi JS, Roh SA, Cho DH, Kim TW, Kim YS. Promoter methylation of specific genes is associated with the phenotype and progression of colorectal adenocarcinomas. Ann Surg Oncol. 2010;17(7):1767–76.CrossRefPubMed
73.
Ang PW, Loh M, Liem N, Lim PL, Grieu F, Vaithilingam A, et al. Comprehensive profiling of DNA methylation in colorectal cancer reveals subgroups with distinct clinicopathological and molecular features. BMC Cancer. 2010;10:227.CrossRefPubMedPubMedCentral
74.
van Roon EH, van Puijenbroek M, Middeldorp A, van Eijk R, de Meijer EJ, Erasmus D, et al. Early onset MSI-H colon cancer with MLH1 promoter methylation, is there a genetic predisposition? BMC Cancer. 2010;10:180.CrossRefPubMedPubMedCentral
75.
Arain MA, Sawhney M, Sheikh S, Anway R, Thyagarajan B, Bond JH, et al. CIMP status of interval colon cancers: another piece to the puzzle. Am J Gastroenterol. 2010;105(5):1189–95.CrossRefPubMed
76.
Dahlin AM, Palmqvist R, Henriksson ML, Jacobsson M, Eklof V, Rutegard J, 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(6):1845–55.CrossRefPubMed
77.
Yagi K, Akagi K, Hayashi H, Nagae G, Tsuji S, Isagawa T, et al. Three DNA methylation epigenotypes in human colorectal cancer. Clin Cancer Res. 2010;16(1):21–33.CrossRefPubMed
78.
Hughes LA, van den Brandt PA, de Bruine AP, Wouters KA, Hulsmans S, Spiertz A, et al. Early life exposure to famine and colorectal cancer risk: a role for epigenetic mechanisms. PLoS One. 2009;4(11):e7951.CrossRefPubMedPubMedCentral
79.
Sanchez JA, Krumroy L, Plummer S, Aung P, Merkulova A, Skacel M, et al. Genetic and epigenetic classifications define clinical phenotypes and determine patient outcomes in colorectal cancer. Br J Surg. 2009;96(10):1196–204.CrossRefPubMed
80.
Seth R, Crook S, Ibrahem S, Fadhil W, Jackson D, Ilyas M. Concomitant mutations and splice variants in KRAS and BRAF demonstrate complex perturbation of the Ras/Raf signalling pathway in advanced colorectal cancer. Gut. 2009;58(9):1234–41.CrossRefPubMed
81.
Ostwald C, Linnebacher M, Weirich V, Prall F. Chromosomally and microsatellite stable colorectal carcinomas without the CpG island methylator phenotype in a molecular classification. Int J Oncol. 2009;35(2):321–7.PubMed
82.
Ang PW, Li WQ, Soong R, Iacopetta B. BRAF mutation is associated with the CpG island methylator phenotype in colorectal cancer from young patients. Cancer Lett. 2009;273(2):221–4.CrossRefPubMed
83.
Barault L, Charon-Barra C, Jooste V, de la Vega MF, Martin L, Roignot P, et al. Hypermethylator phenotype in sporadic colon cancer: study on a population-based series of 582 cases. Cancer Res. 2008;68(20):8541–6.CrossRefPubMed
84.
Fukuyama R, Niculaita R, Ng KP, Obusez E, Sanchez J, Kalady M, et al. Mutated in colorectal cancer, a putative tumor suppressor for serrated colorectal cancer, selectively represses beta-catenin-dependent transcription. Oncogene. 2008;27(46):6044–55.CrossRefPubMedPubMedCentral
85.
Cai G, Xu Y, Lu H, Shi Y, Lian P, Peng J, et al. Clinicopathologic and molecular features of sporadic microsatellite- and chromosomal-stable colorectal cancers. Int J Color Dis. 2008;23(4):365–73.CrossRef
86.
Deng G, Kakar S, Tanaka H, Matsuzaki K, Miura S, Sleisenger MH, et al. Proximal and distal colorectal cancers show distinct gene-specific methylation profiles and clinical and molecular characteristics. Eur J Cancer. 2008;44(9):1290–301.CrossRefPubMed
87.
Kakar S, Deng G, Sahai V, Matsuzaki K, Tanaka H, Miura S, et al. Clinicopathologic characteristics, CpG island methylator phenotype, and BRAF mutations in microsatellite-stable colorectal cancers without chromosomal instability. Arch Pathol Lab Med. 2008;132(6):958–64.PubMed
88.
Suehiro Y, Wong CW, Chirieac LR, Kondo Y, Shen L, Webb CR, et al. Epigenetic-genetic interactions in the APC/WNT, RAS/RAF, and P53 pathways in colorectal carcinoma. Clin Cancer Res. 2008;14(9):2560–9.CrossRefPubMedPubMedCentral
89.
Ferracin M, Gafa R, Miotto E, Veronese A, Pultrone C, Sabbioni S, et al. The methylator phenotype in microsatellite stable colorectal cancers is characterized by a distinct gene expression profile. J Pathol. 2008;214(5):594–602.CrossRefPubMed
90.
Iacopetta B, Grieu F, Phillips M, Ruszkiewicz A, Moore J, Minamoto T, et al. Methylation levels of LINE-1 repeats and CpG island loci are inversely related in normal colonic mucosa. Cancer Sci. 2007;98(9):1454–60.CrossRefPubMed
91.
Goel A, Nagasaka T, Arnold CN, Inoue T, Hamilton C, Niedzwiecki D, et al. The CpG island methylator phenotype and chromosomal instability are inversely correlated in sporadic colorectal cancer. Gastroenterology. 2007;132(1):127–38.CrossRefPubMed
92.
Sugai T, Habano W, Jiao YF, Tsukahara M, Takeda Y, Otsuka K, et al. Analysis of molecular alterations in left- and right-sided colorectal carcinomas reveals distinct pathways of carcinogenesis: proposal for new molecular profile of colorectal carcinomas. J Mol Diagn. 2006;8(2):193–201.CrossRefPubMedPubMedCentral
93.
Tanaka H, Deng G, Matsuzaki K, Kakar S, Kim GE, Miura S, et al. BRAF mutation, CpG island methylator phenotype and microsatellite instability occur more frequently and concordantly in mucinous than non-mucinous colorectal cancer. Int J Cancer. 2006;118(11):2765–71.CrossRefPubMed
94.
Anacleto C, Leopoldino AM, Rossi B, Soares FA, Lopes A, Rocha JC, et al. Colorectal cancer “methylator phenotype”: fact or artifact? Neoplasia. 2005;7(4):331–5.CrossRefPubMedPubMedCentral
95.
Oyama K, Kawakami K, Maeda K, Ishiguro K, Watanabe G. The association between methylenetetrahydrofolate reductase polymorphism and promoter methylation in proximal colon cancer. Anticancer Res. 2004;24(2B):649–54.PubMed
96.
Yamashita K, Dai T, Dai Y, Yamamoto F, Perucho M. Genetics supersedes epigenetics in colon cancer phenotype. Cancer Cell. 2003;4(2):121–31.CrossRefPubMed
97.
Frazier ML, Xi L, Zong J, Viscofsky N, Rashid A, Wu EF, et al. Association of the CpG island methylator phenotype with family history of cancer in patients with colorectal cancer. Cancer Res. 2003;63(16):4805–8.PubMed
98.
van Rijnsoever M, Grieu F, Elsaleh H, Joseph D, Iacopetta B. Characterisation of colorectal cancers showing hypermethylation at multiple CpG islands. Gut. 2002;51(6):797–802.CrossRefPubMedPubMedCentral
99.
Toyota M, Ohe-Toyota M, Ahuja N, Issa JP. Distinct genetic profiles in colorectal tumors with or without the CpG island methylator phenotype. Proc Natl Acad Sci U S A. 2000;97(2):710–5.CrossRefPubMedPubMedCentral
100.
Chen KH, Lin YL, Liau JY, Tsai JH, Tseng LH, Lin LI, et al. BRAF mutation may have different prognostic implications in early- and late-stage colorectal cancer. Med Oncol. 2016;33(5):39.CrossRefPubMed
101.
Carr PR, Jansen L, Walter V, Kloor M, Roth W, Blaker H, et al. Associations of red and processed meat with survival after colorectal cancer and differences according to timing of dietary assessment. Am J Clin Nutr. 2016;103(1):192–200.CrossRefPubMed
102.
Bae JM, Kim JH, Rhee YY, Cho NY, Kim TY, Kang GH. Annexin A10 expression in colorectal cancers with emphasis on the serrated neoplasia pathway. World J Gastroenterol. 2015;21(33):9749–57.CrossRefPubMedPubMedCentral
103.
Ichimura N, Shinjo K, An B, Shimizu Y, Yamao K, Ohka F, et al. Aberrant TET1 methylation closely associated with CpG island methylator phenotype in colorectal cancer. Cancer Prev Res (Phila). 2015;8(8):702–11.CrossRef
104.
Li X, Hu F, Wang Y, Yao X, Zhang Z, Wang F, et al. CpG island methylator phenotype and prognosis of colorectal cancer in Northeast China. Biomed Res Int. 2014;2014:236361.PubMedPubMedCentral
105.
Perea J, Cano JM, Rueda D, Garcia JL, Inglada L, Osorio I, et al. Classifying early-onset colorectal cancer according to tumor location: new potential subcategories to explore. Am J Cancer Res. 2015;5(7):2308–13.PubMedPubMedCentral
106.
Wang Y, Long Y, Xu Y, Guan Z, Lian P, Peng J, et al. Prognostic and predictive value of CpG island methylator phenotype in patients with locally advanced nonmetastatic sporadic colorectal cancer. Gastroenterol Res Pract. 2014;2014:436985.PubMedPubMedCentral
107.
Poole EM, Curtin K, Hsu L, Kulmacz RJ, Duggan DJ, Makar KW, et al. Genetic variability in EGFR, Src and HER2 and risk of colorectal adenoma and cancer. Int J Mol Epidemiol Genet. 2011;2(4):300–15.PubMedPubMedCentral
108.
Cohen SA, Wu C, Yu M, Gourgioti G, Wirtz R, Raptou G, et al. Evaluation of CpG island methylator phenotype as a biomarker in colorectal cancer treated with adjuvant Oxaliplatin. Clin Colorectal Cancer. 2016;15(2):164–9.CrossRefPubMed
109.
Maeda T, Suzuki K, Togashi K, Nokubi M, Saito M, Tsujinaka S, et al. Sessile serrated adenoma shares similar genetic and epigenetic features with microsatellite unstable colon cancer in a location-dependent manner. Exp Ther Med. 2011;2(4):695–700.CrossRefPubMedPubMedCentral
110.
Jia M, Jansen L, Walter V, Tagscherer K, Roth W, Herpel E, et al. No association of CpG island methylator phenotype and colorectal cancer survival: population-based study. Br J Cancer. 2016;115(11):1359–66.CrossRefPubMedPubMedCentral
111.
Ling A, Lundberg IV, Eklof V, Wikberg ML, Oberg A, Edin S, et al. The infiltration, and prognostic importance, of Th1 lymphocytes vary in molecular subgroups of colorectal cancer. J Pathol Clin Res. 2016;2(1):21–31.CrossRefPubMed
112.
Zhang X, Shimodaira H, Soeda H, Komine K, Takahashi H, Ouchi K, et al. CpG island methylator phenotype is associated with the efficacy of sequential oxaliplatin- and irinotecan-based chemotherapy and EGFR-related gene mutation in Japanese patients with metastatic colorectal cancer. Int J Clin Oncol. 2016;21(6):1091–101.CrossRefPubMed
113.
Mima K, Nowak JA, Qian ZR, Cao Y, Song M, Masugi Y, et al. Tumor LINE-1 methylation level and colorectal cancer location in relation to patient survival. Oncotarget. 2016;7(34):55098–109.CrossRefPubMedPubMedCentral
114.
Minarikova P, Benesova L, Halkova T, Belsanova B, Suchanek S, Cyrany J, et al. Longitudinal molecular characterization of endoscopic specimens from colorectal lesions. World J Gastroenterol. 2016;22(20):4936–45.CrossRefPubMedPubMedCentral
115.
Suraweera N, Mouradov D, Li S, Jorissen RN, Hampson D, Ghosh A, et al. Relative telomere lengths in tumor and normal mucosa are related to disease progression and chromosome instability profiles in colorectal cancer. Oncotarget. 2016;7(24):36474–88.CrossRefPubMedPubMedCentral
116.
Sawada T, Yamamoto E, Yamano HO, Nojima M, Harada T, Maruyama R, et al. Assessment of epigenetic alterations in early colorectal lesions containing BRAF mutations. Oncotarget. 2016;7(23):35106–18.CrossRefPubMedPubMedCentral
117.
Hokazono K, Ueki T, Nagayoshi K, Nishioka Y, Hatae T, Koga Y, et al. A CpG island methylator phenotype of colorectal cancer that is contiguous with conventional adenomas, but not serrated polyps. Oncol Lett. 2014;8(5):1937–44.CrossRefPubMedPubMedCentral
118.
Rasuck CG, Leite SM, Komatsuzaki F, Ferreira AC, Oliveira VC, Gomes KB. Association between methylation in mismatch repair genes, V600E BRAF mutation and microsatellite instability in colorectal cancer patients. Mol Biol Rep. 2012;39(3):2553–60.CrossRefPubMed
119.
Van Guelpen B, Dahlin AM, Hultdin J, Eklof V, Johansson I, Henriksson ML, et al. One-carbon metabolism and CpG island methylator phenotype status in incident colorectal cancer: a nested case-referent study. Cancer Causes Control. 2010;21(4):557–66.CrossRefPubMed
120.
Meng H, Li W, Boardman LA, Wang L. Loss of ZG16 is associated with molecular and clinicopathological phenotypes of colorectal cancer. BMC Cancer. 2018;18(1):433.CrossRefPubMedPubMedCentral
121.
Boulagnon-Rombi C, Schneider C, Leandri C, Jeanne A, Grybek V, Bressenot AM, et al. LRP1 expression in colon cancer predicts clinical outcome. Oncotarget. 2018;9(10):8849.CrossRefPubMedPubMedCentral
122.
Fennell LJ, Jamieson S, McKeone D, Corish T, Rohdmann M, Furner T, et al. MLH1–93 G/a polymorphism is associated with MLH1 promoter methylation and protein loss in dysplastic sessile serrated adenomas with BRAF V600E mutation. BMC Cancer. 2018;18(1):35.CrossRefPubMedPubMedCentral
123.
Kokelaar RF, Jones HG, Williamson J, Williams N, Griffiths AP, Beynon J, et al. DNA hypermethylation as a predictor of extramural vascular invasion (EMVI) in rectal cancer. Cancer Biol Ther. 2018;19(3):214–21.CrossRefPubMedPubMedCentral
124.
Saadallah-Kallel A, Abdelmaksoud-Dammak R, Triki M, Charfi S, Khabir A, Sallemi-Boudawara T, et al. Clinical and prognosis value of the CIMP status combined with MLH1 or p16INK4a methylation in colorectal cancer. Med Oncol. 2017;34(8):147.CrossRefPubMed
125.
Alvi MA, Loughrey MB, Dunne P, McQuaid S, Turkington R, Fuchs M-A, et al. Molecular profiling of signet ring cell colorectal cancer provides a strong rationale for genomic targeted and immune checkpoint inhibitor therapies. Br J Cancer. 2017;117(2):203.CrossRefPubMedPubMedCentral
126.
Williamson JS, Jones HG, Williams N, Griffiths AP, Jenkins G, Beynon J, et al. Extramural vascular invasion and response to neoadjuvant chemoradiotherapy in rectal cancer: influence of the CpG island methylator phenotype. World J Gastrointest Oncol. 2017;9(5):209.CrossRefPubMedPubMedCentral
127.
Vedeld HM, Merok M, Jeanmougin M, Danielsen SA, Honne H, Presthus GK, et al. CpG island methylator phenotype identifies high risk patients among microsatellite stable BRAF mutated colorectal cancers. Int J Cancer. 2017;141(5):967–76.CrossRefPubMedPubMedCentral
128.
129.
Cohen SA, Yu M, Baker K, Redman M, Wu C, Heinzerling TJ, et al. The CpG island methylator phenotype is concordant between primary colorectal carcinoma and matched distant metastases. Clin Epigenetics. 2017;9(1):46.CrossRefPubMedPubMedCentral
130.
Lee C-T, Huang Y-C, Hung L-Y, Chow N-H, Su P-F, Ho C-L, et al. Serrated adenocarcinoma morphology in colorectal mucinous adenocarcinoma is associated with improved patient survival. Oncotarget. 2017;8(21):35165.PubMedPubMedCentral
131.
McInnes T, Zou D, Rao DS, Munro FM, Phillips VL, McCall JL, et al. Genome-wide methylation analysis identifies a core set of hypermethylated genes in CIMP-H colorectal cancer. BMC Cancer. 2017;17(1):228.CrossRefPubMedPubMedCentral
132.
Jones HG, Jenkins G, Williams N, Griffiths P, Chambers P, Beynon J, et al. Genetic and epigenetic intra-tumour heterogeneity in colorectal cancer. World J Surg. 2017;41(5):1375–83.CrossRefPubMedPubMedCentral
133.
Kim CH, Huh JW, Kim HR, Kim YJ. CpG island methylator phenotype is an independent predictor of survival after curative resection for colorectal cancer: a prospective cohort study. J Gastroenterol Hepatol. 2017;32(8):1469–74.CrossRefPubMed
134.
135.
Tsoi KK, Pau CY, Wu WK, Chan FK, Griffiths S, Sung JJ. Cigarette smoking and the risk of colorectal cancer: a meta-analysis of prospective cohort studies. Clin Gastroenterol Hepatol. 2009;7(6):682–8. e5.CrossRefPubMed
136.
Bongaerts BW, van den Brandt PA, Goldbohm RA, de Goeij AF, Weijenberg MP. Alcohol consumption, type of alcoholic beverage and risk of colorectal cancer at specific subsites. Int J Cancer. 2008;123(10):2411–7.CrossRefPubMed
137.
Ma Y, Yang Y, Wang F, Zhang P, Shi C, Zou Y, et al. Obesity and risk of colorectal cancer: a systematic review of prospective studies. PLoS One. 2013;8(1):e53916.CrossRefPubMedPubMedCentral
138.
Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol Off J Am Soc Clin Oncol. 2006;24(14):2137–50.CrossRef
139.
Young JP, Win AK, Rosty C, Flight I, Roder D, Young GP, et al. Rising incidence of early-onset colorectal cancer in Australia over two decades: report and review. J Gastroenterol Hepatol. 2015;30(1):6–13.CrossRefPubMed
140.
Sung JJ, Lau JY, Goh KL, Leung WK. Increasing incidence of colorectal cancer in Asia: implications for screening. Lancet Oncol. 2005;6(11):871–6.CrossRefPubMed
141.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.CrossRefPubMed
142.
Center MM, Jemal A, Ward E. International trends in colorectal cancer incidence rates. Cancer Epidemiol Biomark Prev. 2009;18(6):1688–94.CrossRef
143.
Huxley RR, Ansary-Moghaddam A, Clifton P, Czernichow S, Parr CL, Woodward M. The impact of dietary and lifestyle risk factors on risk of colorectal cancer: a quantitative overview of the epidemiological evidence. Int J Cancer. 2009;125(1):171–80.CrossRefPubMed
144.
Hughes LA, Simons CC, van den Brandt PA, Goldbohm RA, de Goeij AF, de Bruine AP, et al. Body size, physical activity and risk of colorectal cancer with or without the CpG island methylator phenotype (CIMP). PLoS One. 2011;6(4):e18571.CrossRefPubMedPubMedCentral
145.
Slattery ML, Curtin K, Sweeney C, Levin TR, Potter J, Wolff RK, et al. Diet and lifestyle factor associations with CpG island methylator phenotype and BRAF mutations in colon cancer. Int J Cancer. 2007;120(3):656–63.CrossRefPubMed
146.
Slattery ML, Wolff RK, Herrick JS, Curtin K, Caan BJ, Samowitz W. Alcohol consumption and rectal tumor mutations and epigenetic changes. Dis Colon Rectum. 2010;53(8):1182–9.CrossRefPubMedPubMedCentral
147.
Ogino S, Nosho K, Irahara N, Meyerhardt JA, Baba Y, Shima K, et al. Lymphocytic reaction to colorectal cancer is associated with longer survival, independent of lymph node count, microsatellite instability, and CpG island methylator phenotype. Clin Cancer Res. 2009;15(20):6412–20.CrossRefPubMedPubMedCentral
148.
Samowitz WS, Albertsen H, Sweeney C, Herrick J, Caan BJ, Anderson KE, et al. Association of smoking, CpG island methylator phenotype, and V600E BRAF mutations in colon cancer. J Natl Cancer Inst. 2006;98(23):1731–8.CrossRefPubMed
149.
Nishihara R, Morikawa T, Kuchiba A, Lochhead P, Yamauchi M, Liao X, et al. A prospective study of duration of smoking cessation and colorectal cancer risk by epigenetics-related tumor classification. Am J Epidemiol. 2013;178(1):84–100.CrossRefPubMedPubMedCentral
150.
Slattery ML, Curtin K, Wolff RK, Herrick JS, Caan BJ, Samowitz W. Diet, physical activity, and body size associations with rectal tumor mutations and epigenetic changes. Cancer Causes Control. 2010;21(8):1237–45.CrossRefPubMedPubMedCentral
151.
Liu L, Nishihara R, Qian ZR, Tabung FK, Nevo D, Zhang X, et al. Association between inflammatory diet pattern and risk of colorectal carcinoma subtypes classified by immune responses to tumor. Gastroenterology. 2017;153(6):1517–30. e14.CrossRefPubMed
152.
Daniel CR, Cross AJ, Koebnick C, Sinha R. Trends in meat consumption in the USA. Public Health Nutr. 2011;14(4):575–83.CrossRefPubMed
153.
Noreen F, Roosli M, Gaj P, Pietrzak J, Weis S, Urfer P, et al. Modulation of age- and cancer-associated DNA methylation change in the healthy colon by aspirin and lifestyle. J Natl Cancer Inst. 2014;106(7):1–9.
154.
English DR, Young JP, Simpson JA, Jenkins MA, Southey MC, Walsh MD, et al. Ethnicity and risk for colorectal cancers showing somatic BRAF V600E mutation or CpG island methylator phenotype. Cancer Epidemiol Biomark Prev. 2008;17(7):1774–80.CrossRef
155.
Curtin K, Samowitz WS, Wolff RK, Caan BJ, Ulrich CM, Potter JD, et al. MSH6 G39E polymorphism and CpG island methylator phenotype in colon cancer. Mol Carcinog. 2009;48(11):989–94.CrossRefPubMedPubMedCentral
156.
Curtin K, Slattery ML, Ulrich CM, Bigler J, Levin TR, Wolff RK, 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(8):1672–9.CrossRefPubMed
157.
158.
Lee S, Cho NY, Yoo EJ, Kim JH, Kang GH. CpG island methylator phenotype in colorectal cancers: comparison of the new and classic CpG island methylator phenotype marker panels. Arch Pathol Lab Med. 2008;132(10):1657–65.PubMed
159.
Kaneda A, Feinberg AP. Loss of imprinting of IGF2: a common epigenetic modifier of intestinal tumor risk. Cancer Res. 2005;65(24):11236–40.CrossRefPubMed
160.
Kaneda A, Yagi K. Two groups of DNA methylation markers to classify colorectal cancer into three epigenotypes. Cancer Sci. 2011;102(1):18–24.CrossRefPubMed
161.
Baylin SB, Ohm JE. Epigenetic gene silencing in cancer - a mechanism for early oncogenic pathway addiction? Nat Rev Cancer. 2006;6(2):107–16.CrossRefPubMed
162.
Feinberg AP, Ohlsson R, Henikoff S. The epigenetic progenitor origin of human cancer. Nat Rev Genet. 2006;7(1):21–33.CrossRefPubMed
163.
Kondo Y, Issa JP. Epigenetic changes in colorectal cancer. Cancer Metastasis Rev. 2004;23(1–2):29–39.CrossRefPubMed
164.
Spring KJ, Zhao ZZ, Karamatic R, Walsh MD, Whitehall VL, Pike T, et al. High prevalence of sessile serrated adenomas with BRAF mutations: a prospective study of patients undergoing colonoscopy. Gastroenterology. 2006;131(5):1400–7.CrossRefPubMed
165.
Leggett B, Whitehall V. Role of the serrated pathway in colorectal cancer pathogenesis. Gastroenterology. 2010;138(6):2088–100.CrossRefPubMed
Metadata
Title
Global differences in the prevalence of the CpG island methylator phenotype of colorectal cancer
Authors
Shailesh Mahesh Advani
Pragati Shailesh Advani
Derek W. Brown
Stacia M. DeSantis
Krittiya Korphaisarn
Helena M. VonVille
Jan Bressler
David S. Lopez
Jennifer S. Davis
Carrie R. Daniel
Amir Mehrvarz Sarshekeh
Dejana Braithwaite
Michael D. Swartz
Scott Kopetz
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2019
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-019-6144-9

Other articles of this Issue 1/2019

BMC Cancer 1/2019 Go to the issue

Research article

Correlation between kidney transplantation and colorectal cancer in hemodialysis patients: A nationwide, retrospective, population-based cohort study

Research article

Clinical insights gained by refining the 2016 WHO classification of diffuse gliomas with: EGFR amplification, TERT mutations, PTEN deletion and MGMT methylation

Research article

Long term follow-up of neoadjuvant chemotherapy for non-small cell lung cancer (NSCLC) investigating early positron emission tomography (PET) scan as a predictor of outcome

Research article

Blood groups A and AB are associated with increased gastric cancer risk: evidence from a large genetic study and systematic review

Research article

Predictors of distant metastasis in parotid acinic cell carcinoma

Research article

Thyroid transcription factor-1 as a prognostic indicator for stage IV lung adenocarcinoma with and without EGFR-sensitizing mutations
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits