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Meta-Analysis
. 2022 Apr;126(7):1067-1081.
doi: 10.1038/s41416-021-01675-5. Epub 2021 Dec 28.

BRCA1 and BRCA2 pathogenic variants and prostate cancer risk: systematic review and meta-analysis

Tommy Nyberg  1   2 , Marc Tischkowitz  3 , Antonis C Antoniou  4
Affiliations
Meta-Analysis

BRCA1 and BRCA2 pathogenic variants and prostate cancer risk: systematic review and meta-analysis

Tommy Nyberg et al. Br J Cancer. 2022 Apr.

Abstract

Background: BRCA1 and BRCA2 pathogenic variants (PVs) are associated with prostate cancer (PCa) risk, but a wide range of relative risks (RRs) has been reported.

Methods: We systematically searched PubMed, Embase, MEDLINE and Cochrane Library in June 2021 for studies that estimated PCa RRs for male BRCA1/2 carriers, with no time or language restrictions. The literature search identified 27 studies (BRCA1: n = 20, BRCA2: n = 21).

Results: The heterogeneity between the published estimates was high (BRCA1: I2 = 30%, BRCA2: I2 = 83%); this could partly be explained by selection for age, family history or aggressive disease, and study-level differences in ethnicity composition, use of historical controls, and location of PVs within BRCA2. The pooled RRs were 2.08 (95% CI 1.38-3.12) for Ashkenazi Jewish BRCA2 carriers, 4.35 (95% CI 3.50-5.41) for non-Ashkenazi European ancestry BRCA2 carriers, and 1.18 (95% CI 0.95-1.47) for BRCA1 carriers. At ages <65 years, the RRs were 7.14 (95% CI 5.33-9.56) for non-Ashkenazi European ancestry BRCA2 and 1.78 (95% CI 1.09-2.91) for BRCA1 carriers.

Conclusions: These PCa risk estimates will assist in guiding clinical management. The study-level subgroup analyses indicate that risks may be modified by age and ethnicity, and for BRCA2 carriers by PV location within the gene, which may guide future risk-estimation studies.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Flowchart.
Flowchart detailing the identification of original research articles on the relative risk of prostate cancer for carriers of BRCA1 and BRCA2 pathogenic variants.
Fig. 2
Fig. 2. Forest plots of overall BRCA1 RR estimates.
a All initially considered studies; b after restriction to studies unselected for age at diagnosis, family history or aggressive disease.
Fig. 3
Fig. 3. Forest plots of overall BRCA2 RR estimates.
a All initially considered studies; b after restriction to studies unselected for age at diagnosis, family history or aggressive disease.
See this image and copyright information in PMC

References

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