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The genetics of hereditary cancer risk syndromes in Brazil: a comprehensive analysis of 1682 patients

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Abstract

Hereditary cancer risk syndromes are caused by germline variants, commonly in tumor suppressor genes. Most studies on hereditary cancer have been conducted in white populations. We report the largest study in Brazilian individuals with multiple ethnicities. We genotyped 1682 individuals from all country regions with Next-generation sequencing (NGS) panels. Most were women with a personal/family history of cancer, mostly breast and ovarian. We identified 321 pathogenic/likely pathogenic (P/LP) variants in 305 people (18.1%) distributed among 32 genes. Most were on BRCA1 and BRCA2 (129 patients, 26.2% and 14.3% of all P/LP, respectively), MUTYH (42 monoallelic patients, 13.1%), PALB2 (25, 7.8%), Lynch syndrome genes (17, 5.3%), and TP53 (17, 5.3%). Transheterozygosity prevalence in our sample was 0.89% (15/1682). BRCA1/BRCA2 double heterozygosity rate was 0.78% (1/129) for BRCA variants carriers and 0.06% (1/1682) overall. We evaluated the performance of the genetic testing criteria by NCCN and the Brazilian National Health Agency (ANS). The inclusion criteria currently used in Brazil fail to identify 17%–25% of carriers of P/LP variants in hereditary cancer genes. Our results add knowledge on the Brazilian spectrum of cancer risk germline variants, demonstrate that large multigene panels have high positivity rates, and indicate that Brazilian inclusion criteria for genetic testing should be improved.

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Fig. 1: Variants profiles.
Fig. 2: Transheterozygotes heatmap.

Data availability

All data generated or analysed during this study are included in this published article and its Supplementary Information Files.

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Correspondence to Jarbas Maciel de Oliveira or João Bosco Oliveira.

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The authors declare no competing interests.

Ethical approval

This project was approved by the Research Ethics Committee of the Institute of Integral Medicine Professor Fernando Figueira (CEP-IMIP) in Recife, Pernambuco and all individuals provided written consent for multi-gene testing (protocol number 29567220.4.1001.0071).

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de Oliveira, J.M., Zurro, N.B., Coelho, A.V.C. et al. The genetics of hereditary cancer risk syndromes in Brazil: a comprehensive analysis of 1682 patients. Eur J Hum Genet 30, 818–823 (2022). https://doi.org/10.1038/s41431-022-01098-7

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