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.

Keywords: BRCA; disparities; germline testing; pancreatic cancer.

Figure 1

Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) flowchart.

Figure 2

Overview of ethnicities in included studies. White patients accounted for 74.7% of all patients enrolled in the 51 studies included in the systematic review and meta-analysis, followed by Asians (17.4%). African Americans and Hispanics were definitely under-tested (1.1% and 2.2%, respectively); the remaining 4.6% gathers uncommon ethnicities (e.g. Hawaiian, Native Americans), Ashkenazi Jewish descendants, mixed ethnicities, and cases of unknown ancestry.

Figure 3

Geographic distribution of studies on germline BRCA in pancreatic cancer. Overview of the geographic distribution of studies included in the systematic review and meta-analysis. The table shows the number of studies per country, including both those conducted in individual countries and international studies. Countries are classified according to the World Bank as lower-middle-income country (LMIC), upper-middle-income country (UMIC), and high-income country (HIC) (https://datahelpdesk.worldbank.org/knowledgebase/articles/906519).