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.

Cancer Prevention and Control Program Lombardi Comprehensive Cancer Center Georgetown University Washington DC 20007 USA

Department of Biostatistics and Data Science School of Public Health The University of Texas Health Science Center at Houston Houston TX 77030 USA

Department of Epidemiology Human Genetics and Environmental Sciences School of Public Health The University of Texas Health Science Center at Houston Houston TX 77030 USA

Department of Epidemiology The University of Texas MD Anderson Cancer Center Houston TX 77030 USA

Department of Gastrointestinal Medical Oncology The University of Texas MD Anderson Cancer Center 1515 Holcombe Blvd Unit 0426 Houston TX 77030 USA

Department of Preventive Medicine and Community Health UTMB Health School of Medicine Galveston TX 77555 1153 USA

Division of Urology UTHealth McGovern Medical School Houston TX 77030 USA

Library School of Public Health The University of Texas Health Science Center at Houston Houston TX 77030 USA

Radiation Epidemiology Branch Division of Cancer Epidemiology and Genetics National Institutes of Health National Cancer Institute Rockville MD 20850 USA

Social Behavioral Research Branch National Human Genome Research Institute National Institute of Health Bethesda MD 20892 USA

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The Role of Tumor Microenvironment and Immune Response in Colorectal Cancer Development and Prognosis