RAPGEF4 – Prostate Cancer

Limited evidence supports RAPGEF4 as a prostate cancer risk gene. A two-stage case–control study sequenced 491 familial or aggressive prostate cancer cases (PMID:32800727) and 429 controls (PMID:32800727) by whole-exome sequencing, then replicated findings in 2917 cases (PMID:32800727) and 1899 controls (PMID:32800727). RAPGEF4 showed a significant increase in rare variant burden among aggressive cases, but no independent segregation data or recurrent pathogenic variants have been reported.

No pathogenic variants have been described at the single-nucleotide or copy-number level, and there is no direct functional work linking RAPGEF4 to prostate tumorigenesis. Although EPAC2 (the protein product of RAPGEF4) modulates cAMP-dependent signaling in other tissues, its role in prostate epithelial proliferation or carcinogenesis remains unexplored. Additional replication studies, detailed variant analysis, and prostate-specific functional assays are needed to clarify clinical utility.

Key Take-home: Current data from a single large case–control study provide limited support for RAPGEF4 in prostate cancer risk; more genetic and functional validation is required before clinical application.

References

• European urology • 2021 • Two-stage Study of Familial Prostate Cancer by Whole-exome Sequencing and Custom Capture Identifies 10 Novel Genes Associated with the Risk of Prostate Cancer. PMID:32800727

Evidence Based Scoring (AI generated)