PROSTATE CANCER — GENETIC TESTING

Prostate Cancer Genetic Testing — approximately 12% of metastatic prostate cancer has germline DNA repair mutations, and PARP inhibitors are FDA-approved for BRCA-mutant castration-resistant prostate cancer.

Whole genome sequencing evaluates all prostate cancer predisposition genes — BRCA2, BRCA1, ATM, CHEK2, HOXB13, PALB2, MSH2, MLH1 — plus pharmacogenomic variants guiding treatment selection.

BRCA2
BRCA1
ATM
HOXB13
CHEK2
PALB2

About this condition

Prostate Cancer — Genetic Testing

Prostate cancer is the most common cancer in men (~290,000 US cases/year). Approximately 5-10% of all prostate cancer and ~12% of metastatic prostate cancer has germline pathogenic variants in DNA repair genes. BRCA2 is the most impactful — conferring 20-30% lifetime risk with significantly earlier onset, higher Gleason grade, and accelerated progression to metastatic disease. HOXB13 G84E is a founder variant in European populations conferring 3-6x risk.

PARP inhibitors have transformed metastatic CRPC treatment for BRCA carriers. Olaparib is FDA-approved for BRCA1/2-mutant mCRPC (PROfound trial — significant OS improvement). Rucaparib is approved for BRCA-mutant mCRPC. NCCN now recommends germline testing for ALL metastatic prostate cancer patients and considers it for high-risk localized disease.

Additional prostate cancer genes include ATM (2-3x risk, sensitivity to PARP inhibitors in trials), CHEK2 (2x risk), PALB2, and Lynch syndrome genes (MSH2, MLH1). The familial component extends beyond these — ~57% heritability with common GWAS variants at >200 loci contributing to polygenic risk.

NCCN recommends germline testing for ALL metastatic prostate cancer patients — ~12% carry actionable variants. Missing BRCA2 means missing olaparib that could extend life.

Gene locus: BRCA2 (13q13.1), BRCA1 (17q21.31), ATM (11q22.3), HOXB13 (17q21.32), CHEK2 (22q12.1), PALB2 (16p12.2)

12% of metastatic prostate cancer has actionable germline variants. PARP inhibitors are FDA-approved for BRCA-mutant mCRPC. WGS captures all DNA repair genes plus treatment-relevant pharmacogenomic variants.

Olaparib extends survival in BRCA-mutant metastatic CRPC — germline testing identifies eligible patients

PROfound demonstrated olaparib significantly improved OS in BRCA1/2 and ATM-mutant mCRPC after progression on enzalutamide/abiraterone. Without germline testing, these patients exhaust standard options without accessing PARP inhibitor therapy.

BRCA2 prostate cancer is aggressive — earlier PSA screening from age 40 for known carriers prevents advanced-stage diagnosis

BRCA2 prostate cancer presents at younger ages with higher Gleason scores. PSA screening from age 40 (vs. standard 50-55) in known BRCA2 carriers enables earlier detection at curable stages. Cascade family testing identifies male relatives who benefit from early screening.

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