The association of retinoic acid receptor beta2(RARβ2) methylation status and prostate cancer risk: a systematic review and meta-analysis

PLoS One. 2013 May 13;8(5):e62950. doi: 10.1371/journal.pone.0062950. Print 2013.

Abstract

The retinoic acid receptor beta2(RARβ2) is a type of nuclear receptor that is activated by both all-trans retinoic acid and 9-cis retinoic acid, which has been shown to function as a tumor suppressor gene in different types of human tumors. Previous reports demonstrated that the frequency of RARβ2 methylation was significantly higher in prostate cancer patients compared with controls, but the relationship between RARβ2 promoter methylation and pathological stage or Gleason score of prostate cancer remained controversial. Therefore, a meta-analysis of published studies investigating the effects of RARβ2 methylation status in prostate cancer occurrence and association with both pathological stage and Gleason score in prostate cancer was performed in the study. A total of 12 eligible studies involving 777 cases and 404 controls were included in the pooled analyses. Under the random-effects model, the pooled OR of RARβ2 methylation in prostate cancer patients, compared to non-cancer controls, was 17.62 with 95%CI = 6.30-49.28. The pooled OR with the fixed-effects model of pathological stage in RASSF1A methylated patients, compared to unmethylated patients, was 0.67 (95%CI = 0.40-1.09) and the pooled OR of low-GS in RARβ2 methylated patients by the random-effect model, compared to high-GS RARβ2 methylated patients, was 0.54 (95%CI = 0.28-1.04). This study showed that RARβ2 might be a potential biomarker in prostate cancer prevention and diagnosis. The detection of RARβ2 methylation in urine or serum is a potential non-invasive diagnostic tool in prostate cancer. The present findings also require confirmation through adequately designed prospective studies.

Publication types

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

MeSH terms

  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / urine
  • Case-Control Studies
  • DNA Methylation
  • Databases, Bibliographic
  • Humans
  • Male
  • Models, Statistical*
  • Neoplasm Staging
  • Promoter Regions, Genetic
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / diagnosis*
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / urine
  • Receptors, Retinoic Acid / blood
  • Receptors, Retinoic Acid / genetics*
  • Tumor Suppressor Proteins / blood
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / urine

Substances

  • Biomarkers, Tumor
  • RASSF1 protein, human
  • Receptors, Retinoic Acid
  • Tumor Suppressor Proteins
  • retinoic acid receptor, beta2, human

Grants and funding

This work was supported by National Natural Science Foundation of China (http://www.nsfc.gov.cn/Portal0/default152.htm) NSFC:C0606. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.