Dataset Information

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

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.

SUBMITTER: Nyberg T

PROVIDER: S-EPMC8979955 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Nyberg Tommy T Tischkowitz Marc M Antoniou Antonis C AC

British journal of cancer 20211228 7

<h4>Background</h4>BRCA1 and BRCA2 pathogenic variants (PVs) are associated with prostate cancer (PCa) risk, but a wide range of relative risks (RRs) has been reported.<h4>Methods</h4>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).<h4>Results</h4>The heterogeneity between the published ...[more]

PMID: 34963702

Similar Datasets

Project description:ImportanceThe clinical importance of genetic testing of BRCA1 and BRCA2 in breast, ovarian, prostate, and pancreatic cancers is widely recognized. However, there is insufficient evidence to include other cancer types that are potentially associated with BRCA1 and BRCA2 in clinical management guidelines.ObjectiveTo evaluate the association of BRCA1 and BRCA2 pathogenic variants with additional cancer types and their clinical characteristics in 100 914 individuals across 14 cancer types.Design, setting, and participantsThis case-control analysis to identify cancer types and clinical characteristics associated with pathogenic variants in BRCA1 and BRCA2 included DNA samples and clinical information from 63 828 patients with 14 common cancer types and 37 086 controls that were sourced from a multi-institutional hospital-based registry, BioBank Japan, between April 2003 and March 2018. The data were analyzed between August 2019 and October 2021.Main outcomes and measuresGermline pathogenic variants in coding regions and 2 bp flanking intronic sequences in BRCA1 and BRCA2 were identified by a multiplex polymerase chain reaction-based target sequence method. Associations of (likely) pathogenic variants with each cancer type were assessed by comparing pathogenic variant carrier frequency between patients in each cancer type and controls.ResultsA total of 65 108 patients (mean [SD] age at diagnosis, 64.1 [11.6] years; 27 531 [42.3%] female) and 38 153 controls (mean [SD] age at registration, 61.8 [14.6] years; 17 911 [46.9%] female) were included in this study. A total of 315 unique pathogenic variants were identified. Pathogenic variants were associated with P < 1 × 10-4 with an odds ratio (OR) of greater than 4.0 in biliary tract cancer (OR, 17.4; 95% CI, 5.8-51.9) in BRCA1, esophageal cancer (OR, 5.6; 95% CI, 2.9-11.0) in BRCA2, and gastric cancer (OR, 5.2; 95% CI, 2.6-10.5) in BRCA1, and (OR, 4.7; 95% CI, 3.1-7.1) in BRCA2 in addition to the 4 established cancer types. We also observed an association with 2 and 4 other cancer types in BRCA1 and BRCA2, respectively. Biliary tract, female breast, ovarian, and prostate cancers showed enrichment of carrier patients according to the increased number of reported cancer types in relatives.Conclusions and relevanceThe results of this large-scale registry-based case-control study suggest that pathogenic variants in BRCA1 and BRCA2 were associated with the risk of 7 cancer types. These results indicate broader clinical relevance of BRCA1 and BRCA2 genetic testing.

Project description:ImportanceWomen with pathogenic variants in BRCA1 and BRCA2 are at high risk of developing breast and ovarian cancers. They usually undergo intensive cancer surveillance and may also consider surgical interventions, such as risk-reducing mastectomy or risk-reducing salpingo-oophorectomy (RRSO). Risk-reducing salpingo-oophorectomy has been shown to reduce ovarian cancer risk, but its association with breast cancer risk is less clear.ObjectiveTo assess the association of RRSO with the risk of breast cancer in women with BRCA1 and BRCA2 pathogenic variants.Design, setting, and participantsThis case series included families enrolled in the Breast Cancer Family Registry between 1996 and 2000 that carried an inherited pathogenic variant in BRCA1 (498 families) or BRCA2 (378 families). A survival analysis approach was used that was designed specifically to assess the time-varying association of RRSO with breast cancer risk and accounting for other potential biases. Data were analyzed from August 2019 to November 2020.ExposureRisk-reducing salpingo-oophorectomy.Main outcomes and measuresIn all analyses, the primary end point was the time to a first primary breast cancer.ResultsA total of 876 families were evaluated, including 498 with BRCA1 (2650 individuals; mean [SD] event age, 55.8 [19.1] years; 437 White probands [87.8%]) and 378 with BRCA2 (1925 individuals; mean [SD] event age, 57.0 [18.6] years; 299 White probands [79.1%]). Risk-reducing salpingo-oophorectomy was associated with a reduced risk of breast cancer for BRCA1 and BRCA2 pathogenic variant carriers within 5 years after surgery (hazard ratios [HRs], 0.28 [95% CI, 0.10-0.63] and 0.19 [95% CI, 0.06-0.71], respectively), whereas the corresponding HRs were weaker after 5 years postsurgery (HRs, 0.64 [95% CI, 0.38-0.97] and 0.99 [95% CI; 0.84-1.00], respectively). For BRCA1 and BRCA2 pathogenic variant carriers who underwent RRSO at age 40 years, the cause-specific cumulative risk of breast cancer was 49.7% (95% CI, 40.0-60.3) and 52.7% (95% CI, 47.9-58.7) by age 70 years, respectively, compared with 61.0% (95% CI, 56.7-66.0) and 54.0% (95% CI, 49.3-60.1), respectively, for women without RRSO.Conclusions and relevanceAlthough the primary indication for RRSO is the prevention of ovarian cancer, it is also critical to assess its association with breast cancer risk in order to guide clinical decision-making about RRSO use and timing. The results of this case series suggest a reduced risk of breast cancer associated with RRSO in the immediate 5 years after surgery in women carrying BRCA1 and BRCA2 pathogenic variants, and a longer-term association with cumulative breast cancer risk in women carrying BRCA1 pathogenic variants.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets