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Factors predicting BRCA1/2 pathogenic variants in patients with ovarian cancer: a systematic review with meta-analysis
  1. Giovanni Innella1,2,
  2. Lea Godino2,
  3. Giulia Erini2,
  4. Antonio De Leo1,3,
  5. Donatella Santini4,
  6. Anna Myriam Perrone2,5,
  7. Pierandrea De Iaco1,5,
  8. Claudio Zamagni6,
  9. Daniela Turchetti1,2
  1. 1 Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
  2. 2 Medical Genetics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
  3. 3 Solid Tumor Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
  4. 4 Department of Pathology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
  5. 5 Division of Oncologic Gynecology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
  6. 6 IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
  1. Correspondence to Dr Lea Godino, Medical Genetics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; lea.godino2{at}


Aim To provide accurate figures of the frequency of specific clinical features in ovarian cancer (OC) associated with germline BRCA1/2 pathogenic variants and to define their relevance in predicting the presence of a germline pathogenic variant in these genes.

Methods A systematic review of papers published from 1995 to February 2022 was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data from eligible papers were synthesised through meta-analysis.

Results Thirty-seven papers were reviewed, including a total of 12 886 patients with OC. Among BRCA carriers, 86.4% displayed serous type, 83.3% high grade (G3), 83.7% FIGO (The International Federation of Gynecology and Obstetrics) stage III/IV, 39.7% age at diagnosis ≤50 years and 18.1% personal breast cancer history, while the frequency of these features in non-carriers resulted significantly lower (p<0.001). The meta-analysis showed that the strongest predictor of BRCA1/2 pathogenic variants was a personal breast cancer history (OR 5.21, 95% CI 4.02 to 6.55, compared with no previous breast cancer), followed by high grade (OR 2.47, 95% CI 1.97 to 3.10, compared with low/intermediate grade), serous histotype (OR 2.33, 95% CI 2.07 to 2.64, compared with other histotypes), advanced (III/IV) FIGO stage (OR 1.89, 95% CI 1.67 to 2.15, compared with stage I/II) and age at diagnosis ≤50 years (OR 1.20, 95% CI 1.01 to 1.42, compared with >50 years).

Conclusion The results of this meta-analysis provide data on features increasing the prior probability of finding BRCA1/2 pathogenic variants that may prove helpful in counselling patients and prioritising testing.

PROSPERO registration number CRD42021271815.

  • ovarian neoplasms
  • genetics
  • ovary

Data availability statement

Data are available on reasonable request.

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Data availability statement

Data are available on reasonable request.

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  • Handling editor Vikram Deshpande.

  • Contributors All the authors conceived the study. LG and DT designed the analytical plan and supervised the study. GE performed the literature search, all the authors contributed to paper selection. GI and LG performed quality assessment. All the authors contributed to extracting and analysing data from selected papers. GI and LG drafted the manuscript. DT revised the manuscript and acts as the guarantor. All the authors approved the final version.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.