Meta-Analysis of BRCA1 and BRCA2 Penetrance
Open accessAbstract
Purpose: Genetic counseling is now routinely offered to individuals at high risk of carrying a BRCA1 or BRCA2 mutation. Risk prediction provided by the counselor requires reliable estimates of the mutation penetrance. Such penetrance has been investigated by studies worldwide. The reported estimates vary. To facilitate clinical management and counseling of the at-risk population, we address this issue through a meta-analysis. Methods: We conducted a literature search on PubMed and selected studies that had nonoverlapping patient data, contained genotyping information, used statistical methods that account for the ascertainment, and reported risks in a useable format. We subsequently combined the published estimates using the DerSimonian and Laird random effects modeling approach. Results: Ten studies were eligible under the selection criteria. Between-study heterogeneity was observed. Study population, mutation type, design, and estimation methods did not seem to be systematic sources of heterogeneity. Meta-analytic mean cumulative cancer risks for mutation carriers at age 70 years were as follows: breast cancer risk of 57% (95% CI, 47% to 66%) for BRCA1 and 49% (95% CI, 40% to 57%) for BRCA2 mutation carriers; and ovarian cancer risk of 40% (95% CI, 35% to 46%) for BRCA1 and 18% (95% CI, 13% to 23%) for BRCA2 mutation carriers. We also report the prospective risks of developing cancer for currently asymptomatic carriers. Conclusion: This article provides a set of risk estimates for BRCA1 and BRCA2 mutation carriers that can be used by counselors and clinicians who are interested in advising patients based on a comprehensive set of studies rather than one specific study.
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The lifetime risk of developing breast cancer in BRCA1/2 mutation carriers ranges from 45 to 80%.
“the lifetime risk of developing breast cancer in BRCA1/2 mutation carriers ranges from 45 to 80% [8–11]”
From Fear of cancer recurrence in breast cancer survivors carrying a BRCA1 or 2 genetic mutation : a cross-sectional study (2024) · cites this paper as [8]
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“Depending on the study, the lifetime risk of developing breast cancer in BRCA1/2 mutation carriers ranges from 45 to 80% [8–11], which is much higher than in the general population (13”
Background
- Authors
- Chen, S., & Parmigiani, G.
- Affiliations
- Johns Hopkins University (US)
- Venue
- Journal of Clinical Oncology
- Published
- 2007-04-10
- Volume
- 25
- Issue
- 11
- Pages
- 1329-1333
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- PMC
- PMC2267287
- OpenAlex
- W2110137106
- Cited by
- 1,802
- References
- 20
- Citations by year
- 2026: 39 · 2025: 76 · 2024: 86 · 2023: 92 · 2022: 99 · 2021: 124 · 2020: 111 · 2019: 115 · 2018: 123 · 2017: 167 · 2016: 158 · 2015: 122 · 2014: 102 · 2013: 98 · 2012: 81
- FWCI
- 4.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL99-024)
- National Cancer Institute (P50-CA-88843, P50CA62924-05, P50CA088843, 5P30CA06973-39, R01CA105090, P50CA062924, P30CA006973)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Health Sciences › Medicine › Epidemiology › Multiple and Secondary Primary Cancers
- Keywords
- BRCA1, BRCA2, mutation penetrance, breast cancer risk, ovarian cancer risk, cumulative cancer risk, mutation carriers, genetic counseling, risk prediction, ascertainment bias
- MeSH terms
- Breast Neoplasms, Female, Genetic Counseling, Genetic Testing, Genotype, Humans, Mutation, Ovarian Neoplasms, Genes, BRCA1, Penetrance, Genetic Predisposition to Disease, Genes, BRCA2
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