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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number964
JournalBMC Cancer
Volume19
Issue number1
DOIs
StatePublished - Oct 17 2019

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Keywords

  • CIMP
  • Colorectal
  • Epigenetics
  • Geographic
  • Methylation

ASJC Scopus subject areas

  • Genetics
  • Oncology
  • Cancer Research

Cite this

Advani, S. M., Advani, P. S., Brown, D. W., Desantis, S. M., Korphaisarn, K., Vonville, H. M., Bressler, J., Lopez, D. S., Davis, J. S., Daniel, C. R., Sarshekeh, A. M., Braithwaite, D., Swartz, M. D., & Kopetz, S. (2019). Global differences in the prevalence of the CpG island methylator phenotype of colorectal cancer. BMC Cancer, 19(1), [964]. https://doi.org/10.1186/s12885-019-6144-9