Meta-analysis of BRCA1 and BRCA2 penetrance

Abstract

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.

Conflict of interest statement

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The authors indicated no potential conflicts of interest

Figures

Fig 1

(A) Breast cancer risk for BRCA1 carriers, (B) breast cancer for BRCA2 carriers, (C) ovarian cancer for BRCA1 carriers, and (D) ovarian cancer for BRCA2 carriers. The cumulative risk estimates from published studies (thin vertical bars) and the meta-analytic mean (thick vertical bars, height represents 95% CIs). Within each 10-year age interval, the published studies are arranged in the following order (left to right): Ford et al and Easton et al, Struewing et al, Hopper et al, Satagopan et al,, Scott et al, Antoniou et al, King et al, Marroni et al, and Chen et al. An “x” represents not available.