A comprehensive literature review and meta-analysis of the prevalence of pan-cancer BRCA mutations, homologous recombination repair gene mutations, and homologous recombination deficiencies

Environ Mol Mutagen. 2022 Jul;63(6):308-316. doi: 10.1002/em.22505. Epub 2022 Aug 30.


There is significant improvement in the outcomes following treatment with PARP inhibitors among patients with certain tumors that have BRCA mutations (BRCAm), homologous recombination repair (HRR) gene mutations, or homologous recombination deficiency (HRD) positivity. We performed a literature review and meta-analysis to evaluate the prevalence of BRCA1/2m, HRR gene mutations, and HRD positivity across multiple cancers. There were 265 publications on BRCA1/2 mutation prevalence, 189 on HRR gene mutation prevalence, and 7 on HRD positivity prevalence. The prevalences of germline BRCA1m and BRCA2m were 7.8% and 5.7% for breast cancer, 13.5% and 6.6% for ovarian cancer, 0.5% and 3.5% for prostate cancer, and 1.1% and 4.1% for pancreatic cancer, respectively. The prevalences of somatic BRCA1m and BRCA2m were 3.4% and 2.7% for breast cancer, 4.7% and 2.9% for ovarian cancer, 5.7% and 3.2% for prostate cancer, and 1.2% and 2.9% for pancreatic cancer, respectively. We identified 189 studies with over 418,649 samples across 25 tumor types that examined mutations in one or more HRR genes other than BRCA1/2. The prevalence of mutations among HRR genes remained low (less than 1%), with ATM (5.2%), CHEK2 (1.6%), and PALB2 (0.9%) exhibiting the highest prevalence. Seven studies evaluated HRD positivity in breast, ovarian, and prostate cancer patients. The prevalence of HRD positivity was 56% overall (95% CI = 48%-64%). The understanding of biomarker prevalence across tumor types and standardization of biomarker assays could have important clinical implications.

Keywords: BRCA; cancer; homologous recombination deficiencies; homologous recombination gene; mutations.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • BRCA1 Protein / genetics*
  • BRCA2 Protein / genetics*
  • Breast Neoplasms* / genetics
  • Female
  • Homologous Recombination
  • Humans
  • Male
  • Mutation
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / epidemiology
  • Ovarian Neoplasms* / genetics
  • Pancreatic Neoplasms*
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use
  • Prevalence
  • Prostatic Neoplasms*
  • Recombinational DNA Repair / genetics


  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Poly(ADP-ribose) Polymerase Inhibitors