Some studies suggest that individuals with Latin American or African ancestry have a higher prevalence of PVs 7 while others demonstrated a lower yield among Hispanic immigrants in the United States (U.S.) 12. From published high risk clinic series, approximately 10% of women meeting National Comprehensive Cancer Network (NCCN) genetic testing criteria will carry a BRCA PV 5, 11. However, a higher rate of PVs has been reported in some founder populations such as the Ashkenazi Jewish, with a PV prevalence of 1/40 10. For example, just 3.4% of participants were Hispanic in a recent study of female PV carriers from 69 centers in 49 countries on 6 continents 9.īRCA PVs are present in around 1/800 people in the general population. However, Hispanics are not well represented in most studies 7, 8. We previously reported a high rate of BRCA PVs among 110 United States (U.S.) Hispanics with early-onset breast cancer 6.
The identification of PVs in at-risk individuals has significant clinical utility, as there are effective interventions aimed at both cancer prevention and early diagnosis 5. Women with likely pathogenic and pathogenic variants (PVs) in either of these genes, have up to 80% lifetime risk of breast cancer and 20–50% risk of ovarian cancer 4. Hereditary breast and ovarian cancer (HBOC) syndrome accounts for approximately 10% of all breast cancer and 15–20% of ovarian cancer cases, and the most commonly associated genes with HBOC are BRCA1 and BRCA2 ( BRCA) 3. Thus, strategies aimed at preventing, or detecting breast cancer at an earlier stage, are crucial within the region. Also, the mean age at diagnosis is younger than US non-Hispanic white (NHW) populations and there is a high prevalence of hormone receptor and Her2 negative breast cancer (TNBC), features common in hereditary disease. High mortality rates in the region are driven in part by advanced stage at diagnosis and limited access to cancer care 2. This study helps address the gap in our understanding of BRCA-associated cancer in Latin America.īreast cancer is the most frequently diagnosed cancer and the leading cause of cancer-related mortality in Latin American women 1. There are recurrent, population-specific PVs and CNVs, and we note that the BRCAPRO mutation probability model performs adequately. In summary, we implemented a low-cost BRCA testing strategy and documented a significant burden of non-ClinVar reported BRCA PVs among Latin Americans. The area under the ROC curve for BRCAPRO was 0.76. There was no ClinVar entry for 14% (17/125) of unique PVs, and 57% (111/196) of unique VUS. Recurrent PVs (seen ≥3 times), some region-specific, represented 42.8% (101/236) of PVs. Among 1,627 participants (95.2% with cancer), we detected 236 (14.5%) BRCA PVs 160 BRCA1 (31% CNVs) 76 BRCA2 PV frequency varied by country: 26% Brazil, 9% Colombia, 13% Peru, and 17% Mexico.
BRCA PV probability was calculated using BRCAPRO. BRCA analyses were performed on prospectively enrolled Latin American Clinical Cancer Genomics Community Research Network participants via a combination of methods: a Hispanic Mutation Panel ( HISPANEL) on MassARRAY semiconductor sequencing and copy number variant (CNV) detection. This study aims to address this disparity.
The prevalence and contribution of BRCA1/ 2 ( BRCA) pathogenic variants (PVs) to the cancer burden in Latin America are not well understood. Npj Breast Cancer volume 7, Article number: 107 ( 2021) Genetic epidemiology of BRCA1- and BRCA2-associated cancer across Latin America
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