A systematic review and meta-analysis of germline BRCA mutations in pancreatic cancer patients identifies global and racial disparities in access to genetic testing

Abstract

Background

Germline BRCA1 and BRCA2 mutations (gBRCAm) can inform pancreatic cancer (PC) risk and treatment but most of the available information is derived from white patients. The ethnic and geographic variability of gBRCAm prevalence and of germline BRCA (gBRCA) testing uptake in PC globally is largely unknown.

Materials and methods

We carried out a systematic review and prevalence meta-analysis of gBRCA testing and gBRCAm prevalence in PC patients stratified by ethnicity . The main outcome was the distribution of gBRCA testing uptake across diverse populations worldwide. Secondary outcomes included: geographic distribution of gBRCA testing uptake, temporal analysis of gBRCA testing uptake in ethnic groups, and pooled proportion of gBRCAm stratified by ethnicity. The study is listed under PROSPERO registration number #CRD42022311769.

Results

A total of 51 studies with 16 621 patients were included. Twelve of the studies (23.5%) enrolled white patients only, 10 Asians only (19.6%), and 29 (56.9%) included mixed populations. The pooled prevalence of white, Asian, African American, and Hispanic patients tested per study was 88.7%, 34.8%, 3.6%, and 5.2%, respectively. The majority of included studies were from high-income countries (HICs) (64; 91.2%). Temporal analysis showed a significant increase only in white and Asians patients tested from 2000 to present ( P < 0.001). The pooled prevalence of gBRCAm was: 3.3% in white, 1.7% in Asian, and negligible (<0.3%) in African American and Hispanic patients.

Conclusions

Data on gBRCA testing and gBRCAm in PC derive mostly from white patients and from HICs. This limits the interpretation of gBRCAm for treating PC across diverse populations and implies substantial global and racial disparities in access to BRCA testing in PC.

Highlights

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  gBRCA testing is relevant for precision PC treatment and more broad cancer screening strategies.

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  Little is known about the ethnicity of PC patients tested for germline BRCA1/2 mutations.

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  We show that most PC patients tested for germline BRCA1/2 mutations in research context are white (74.7%) and from high-income countries (91.2%).

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  These findings implie major global and ethnic disparities in access to gBRCA testing for patients with PC.

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  Global efforts are urgently needed to promote accessibility of non-white patients to gBRCA testing and, in general, to clinical trials.