Association between gene promoter methylation and cervical cancer development: global distribution and a meta-analysis

Abstract

DNA methylation is the main epigenetic event for gene silencing and is associated with carcinogenesis. In this meta-analysis, we evaluated the association between the methylation of the promoter regions of APC, CADM1, CCNA1, CDH1, DAPK, FHIT, HIC1, MAL, MGMT, hMLH1, p16, PAX1, RAR-β, and RASSF1 genes and the risk of cervical cancer development and progression. Overall, 194 eligible studies were identified assessing the associations of APC, CADM1, CCNA1, CDH1, DAPK, FHIT, HIC1, MAL, MGMT, hMLH1, p16, PAX1, RAR-β and RASSF1 promoters methylation status with LSIL, HSIL and cervical cancer development. Almost studies were conducted on Caucasian and Asian populations whereas limited data are available from African population. Promoters methylation frequencies were shown to be significantly higher in LSIL, HSIL cervical cancer cases as compared to control specimens for CADM1, CCNA1, CDH1, DAPK1, FHIT, MAL, P16, PAX1, RAR-β, and RASSF1 genes. A moderate association was found between HIC promoter methylation whereas APC, MGMT, and hMLH1 promoters' methylation was not correlated with cervical cancer development. Promoters methylation could be considered as a non-invasive biomarker for early cervical lesions, making them highly promising targets for a personalized therapeutic approach.