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
Affiliations
Shailesh Mahesh Advani
Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center
Pragati Shailesh Advani
Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Institutes of Health, National Cancer Institute
Derek W. Brown
Department of Biostatistics and Data Science, School of Public Health, The University of Texas Health Science Center at Houston
Stacia M. DeSantis
Department of Biostatistics and Data Science, School of Public Health, The University of Texas Health Science Center at Houston
Krittiya Korphaisarn
Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center
Helena M. VonVille
Library, School of Public Health, The University of Texas Health Science Center at Houston
Jan Bressler
Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston
David S. Lopez
Division of Urology- UTHealth McGovern Medical School
Jennifer S. Davis
Department of Epidemiology, The University of Texas MD Anderson Cancer Center
Carrie R. Daniel
Department of Epidemiology, The University of Texas MD Anderson Cancer Center
Amir Mehrvarz Sarshekeh
Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center
Dejana Braithwaite
Cancer Prevention and Control Program, Lombardi Comprehensive Cancer Center, Georgetown University
Michael D. Swartz
Department of Biostatistics and Data Science, School of Public Health, The University of Texas Health Science Center at Houston
Scott Kopetz
Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center
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.
