Association between RASSF1A Promoter Hypermethylation and Oncogenic HPV Infection Status in Invasive Cervical Cancer: a Meta-analysis

Asian Pac J Cancer Prev. 2015;16(14):5749-54. doi: 10.7314/apjcp.2015.16.14.5749.

Abstract

Cervical carcinoma is the main cause of cancer-related mortality in women and is correlated with more than 15 risk cofactors, including infection of cervical cells with high-risk types of HPV (hrHPV). Indeed, both aberrant methylation of the RASSF1A promoter and hrHPV infection are often observed in cervical carcinomas. The purpose of our meta-analysis was to evaluate the role of RASSF1A promoter methylation and hrHPV infection in cervical cancer. Our meta-analysis involved 895 cervical cancer patients and 454 control patients from 15 studies. Our results suggested that RASSF1A promoter hypermethylation increased the risk of cervical cancer (OR=9.77, 95%CI=[3.06, 31.26], P=0.0001, I2=78%). By grouping cases according to cancer subtypes, we found that HPV infection was higher in cervical squamous cell carcinomas (SCCs) than in cervical adenocarcinomas/ adenosquamous cancers (ACs/ASCs) (OR=4.00, 95%CI=[1.41, 11.30], P=0.009, I2=55%). Interestingly, HPV infection tended to occur in cervical cancers with relatively low levels of RASSF1A promoter methylation (OR=0.59, 95%CI=[0.36, 0.99], P=0.05, I2=0%). Our study provides evidence of a possible interaction between HPV infection and RASSF1A promoter methylation in the development of cervical cancers.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / etiology*
  • Adenocarcinoma / pathology
  • Carcinoma, Squamous Cell / etiology*
  • Carcinoma, Squamous Cell / pathology
  • DNA Methylation*
  • Female
  • Humans
  • Neoplasm Invasiveness
  • Papillomaviridae / genetics*
  • Papillomaviridae / pathogenicity
  • Papillomavirus Infections / complications
  • Papillomavirus Infections / genetics*
  • Papillomavirus Infections / virology
  • Polymerase Chain Reaction
  • Prognosis
  • Promoter Regions, Genetic / genetics*
  • Tumor Suppressor Proteins / genetics*
  • Uterine Cervical Neoplasms / etiology*
  • Uterine Cervical Neoplasms / pathology

Substances

  • RASSF1 protein, human
  • Tumor Suppressor Proteins