Abstract
BackgroundCpG 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.MethodsWe 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.ResultsThe 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.ConclusionAlthough 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.
Highlights
CpG Island Methylator Phenotype (CIMP) is an epigenetic phenotype in Colorectal cancer (CRC) characterized by hypermethylation of CpG islands in promoter regions of tumor suppressor genes, leading to their transcriptional silencing and loss of function
Of total 749 screened, 279 articles were excluded because they did not report original research, 43 articles did not include a clear description of CIMP, and 90 articles were excluded for other reasons, including a focus on premalignant lesions such as adenomas or polyps or inadequate information on CIMP measurements or methodologies
The pooled prevalence of CIMP -High (CIMP-H) varied from 21 to 27% across geographical regions, and metaregression analysis did not identify any significant differences in pooled prevalence across geographical regions, after adjusting for methodological differences
Summary
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. One type of epigenetic alteration associated with cancer is methylation of CpG islands in promoter regions of tumor suppressor genes which form hotspots for methylation changes. CIMP -High (CIMP-H) is considered a distinct molecular subtype of sporadic colorectal cancer. It is characterized by a high degree of methylation in promoterassociated CpG-rich regions of tumor suppressor genes, which causes transcriptional inactivation of these genes and leads to cancer development and progression [4, 8]
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