Somatic DNA Damage Response and Homologous Repair Gene Alterations and Its Association With Tumor Variant Burden in Breast Cancer Patients With Occupational Exposure to Pesticides

Detalhes bibliográficos
Autor(a) principal: Scandolara, Thalita Basso
Data de Publicação: 2022
Outros Autores: Valle, Sara Ferreira, Esteves, Cristiane, Scherer, Nicole de Miranda, Armas, Elvismary Molina de, Furtado, Carolina, Gomes, Renan, Boroni, Mariana, Jaques, Hellen dos Santos, Alves, Fernanda Mara, Rech, Daniel, Panis, Carolina, Bonvicino, Cibele Rodrigues
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
DOI: 10.3389/fonc.2022.904813
Texto Completo: https://www.arca.fiocruz.br/handle/icict/56228
Resumo: Universidade Federal do Rio de Janeiro. Instituto de Biologia. Departamento de Genética. Rio de Janeiro, RJ, Brasil.
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spelling Scandolara, Thalita BassoValle, Sara FerreiraEsteves, CristianeScherer, Nicole de MirandaArmas, Elvismary Molina deFurtado, CarolinaGomes, RenanBoroni, MarianaJaques, Hellen dos SantosAlves, Fernanda MaraRech, DanielPanis, CarolinaBonvicino, Cibele Rodrigues2022-12-30T21:39:11Z2022-12-30T21:39:11Z2022SCANDOLARA, Thalita Basso et al. Somatic DNA Damage Response and Homologous Repair Gene Alterations and Its Association With Tumor Variant Burden in Breast Cancer Patients With Occupational Exposure to Pesticides. Frontiers in Oncology, v. 12, Article 904813, p. 1 - 13, July 2022.2234-943Xhttps://www.arca.fiocruz.br/handle/icict/5622810.3389/fonc.2022.904813engFrontiers MediaCâncer de mamaPesticidasExposição profissionalCarga mutacionalSomáticaBreast cancerPesticidesOccupational exposureMutational burdenSomaticSomatic DNA Damage Response and Homologous Repair Gene Alterations and Its Association With Tumor Variant Burden in Breast Cancer Patients With Occupational Exposure to Pesticidesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal do Rio de Janeiro. Instituto de Biologia. Departamento de Genética. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biologia. Departamento de Genética. Rio de Janeiro, RJ, Brasil.Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA). Bioinformática e Laboratório de Biologia Computacional. Rio de Janeiro, RJ, Brasil.Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA). Bioinformática e Laboratório de Biologia Computacional. Rio de Janeiro, RJ, Brasil.Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA). Bioinformática e Laboratório de Biologia Computacional. Rio de Janeiro, RJ, Brasil / Pontificia Universidade Católica (PUC)-Rio. Departamento de Informática. Rio de Janeiro, RJ, Brasil.Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA). Divisão de Genética. Rio de Janeiro, RJ, Brasil.Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA). Divisão de Genética. Rio de Janeiro, RJ, Brasil.Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA). Bioinformática e Laboratório de Biologia Computacional. Rio de Janeiro, RJ, Brasil.Universidade do Oeste do Paraná. Laboratório de Biologia Tumoral. Francisco Beltrão, PR, Brasil.Universidade do Oeste do Paraná. Laboratório de Biologia Tumoral. Francisco Beltrão, PR, Brasil.Universidade do Oeste do Paraná. Laboratório de Biologia Tumoral. Francisco Beltrão, PR, Brasil / Francisco Beltrão Cancer Hospital, Francisco Beltrão, PR, Brasil.Universidade do Oeste do Paraná. Laboratório de Biologia Tumoral. Francisco Beltrão, PR, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biologia. Departamento de Genética. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA). Divisão de Genética. Rio de Janeiro, RJ, Brasil.Homologous recombination is a crucial pathway that is specialized in repairing doublestrand breaks; thus, alterations in genes of this pathway may lead to loss of genomic stability and cell growth suppression. Pesticide exposure potentially increases cancer risk through several mechanisms, such as the genotoxicity caused by chronic exposure, leading to gene alteration. To analyze this hypothesis, we investigated if breast cancer patients exposed to pesticides present a different mutational pattern in genes related to homologous recombination (BRCA1, BRCA2, PALB2, and RAD51D) and damageresponse (TP53) concerning unexposed patients. We performed multiplex PCR-based assays and next-generation sequencing (NGS) of all coding regions and flanking splicing sites of BRCA1, BRCA2, PALB2, TP53, and RAD51D in 158 unpaired tumor samples from breast cancer patients on MiSeq (Illumina) platform. We found that exposed patients had tumors with more pathogenic and likely pathogenic variants than unexposed patients (p = 0.017). In general, tumors that harbored a pathogenic or likely pathogenic variant had a higher mutational burden (p < 0.001). We also observed that breast cancer patients exposed to pesticides had a higher mutational burden when diagnosed before 50 years old (p = 0.00978) and/or when carrying BRCA1 (p = 0.0138), BRCA2 (p = 0.0366), and/or PALB2 (p = 0.00058) variants, a result not found in the unexposed group. Our results show that pesticide exposure impacts the tumor mutational landscape and could be associated with the carcinogenesis process, therapy response, and disease progression. Further studies should increase the observation period in exposed patients to better evaluate the impact of these findings.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/56228/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALCibele_BOnvicino_etal_2022.pdfCibele_BOnvicino_etal_2022.pdfapplication/pdf5345079https://www.arca.fiocruz.br/bitstream/icict/56228/2/Cibele_BOnvicino_etal_2022.pdf339e51c87d0fb808503f588a3ddac30eMD52icict/562282023-09-04 11:03:19.595oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-09-04T14:03:19Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.en_US.fl_str_mv Somatic DNA Damage Response and Homologous Repair Gene Alterations and Its Association With Tumor Variant Burden in Breast Cancer Patients With Occupational Exposure to Pesticides
title Somatic DNA Damage Response and Homologous Repair Gene Alterations and Its Association With Tumor Variant Burden in Breast Cancer Patients With Occupational Exposure to Pesticides
spellingShingle Somatic DNA Damage Response and Homologous Repair Gene Alterations and Its Association With Tumor Variant Burden in Breast Cancer Patients With Occupational Exposure to Pesticides
Scandolara, Thalita Basso
Câncer de mama
Pesticidas
Exposição profissional
Carga mutacional
Somática
Breast cancer
Pesticides
Occupational exposure
Mutational burden
Somatic
title_short Somatic DNA Damage Response and Homologous Repair Gene Alterations and Its Association With Tumor Variant Burden in Breast Cancer Patients With Occupational Exposure to Pesticides
title_full Somatic DNA Damage Response and Homologous Repair Gene Alterations and Its Association With Tumor Variant Burden in Breast Cancer Patients With Occupational Exposure to Pesticides
title_fullStr Somatic DNA Damage Response and Homologous Repair Gene Alterations and Its Association With Tumor Variant Burden in Breast Cancer Patients With Occupational Exposure to Pesticides
title_full_unstemmed Somatic DNA Damage Response and Homologous Repair Gene Alterations and Its Association With Tumor Variant Burden in Breast Cancer Patients With Occupational Exposure to Pesticides
title_sort Somatic DNA Damage Response and Homologous Repair Gene Alterations and Its Association With Tumor Variant Burden in Breast Cancer Patients With Occupational Exposure to Pesticides
author Scandolara, Thalita Basso
author_facet Scandolara, Thalita Basso
Valle, Sara Ferreira
Esteves, Cristiane
Scherer, Nicole de Miranda
Armas, Elvismary Molina de
Furtado, Carolina
Gomes, Renan
Boroni, Mariana
Jaques, Hellen dos Santos
Alves, Fernanda Mara
Rech, Daniel
Panis, Carolina
Bonvicino, Cibele Rodrigues
author_role author
author2 Valle, Sara Ferreira
Esteves, Cristiane
Scherer, Nicole de Miranda
Armas, Elvismary Molina de
Furtado, Carolina
Gomes, Renan
Boroni, Mariana
Jaques, Hellen dos Santos
Alves, Fernanda Mara
Rech, Daniel
Panis, Carolina
Bonvicino, Cibele Rodrigues
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Scandolara, Thalita Basso
Valle, Sara Ferreira
Esteves, Cristiane
Scherer, Nicole de Miranda
Armas, Elvismary Molina de
Furtado, Carolina
Gomes, Renan
Boroni, Mariana
Jaques, Hellen dos Santos
Alves, Fernanda Mara
Rech, Daniel
Panis, Carolina
Bonvicino, Cibele Rodrigues
dc.subject.other.en_US.fl_str_mv Câncer de mama
Pesticidas
Exposição profissional
Carga mutacional
Somática
topic Câncer de mama
Pesticidas
Exposição profissional
Carga mutacional
Somática
Breast cancer
Pesticides
Occupational exposure
Mutational burden
Somatic
dc.subject.en.en_US.fl_str_mv Breast cancer
Pesticides
Occupational exposure
Mutational burden
Somatic
description Universidade Federal do Rio de Janeiro. Instituto de Biologia. Departamento de Genética. Rio de Janeiro, RJ, Brasil.
publishDate 2022
dc.date.accessioned.fl_str_mv 2022-12-30T21:39:11Z
dc.date.available.fl_str_mv 2022-12-30T21:39:11Z
dc.date.issued.fl_str_mv 2022
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv SCANDOLARA, Thalita Basso et al. Somatic DNA Damage Response and Homologous Repair Gene Alterations and Its Association With Tumor Variant Burden in Breast Cancer Patients With Occupational Exposure to Pesticides. Frontiers in Oncology, v. 12, Article 904813, p. 1 - 13, July 2022.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/56228
dc.identifier.issn.en_US.fl_str_mv 2234-943X
dc.identifier.doi.none.fl_str_mv 10.3389/fonc.2022.904813
identifier_str_mv SCANDOLARA, Thalita Basso et al. Somatic DNA Damage Response and Homologous Repair Gene Alterations and Its Association With Tumor Variant Burden in Breast Cancer Patients With Occupational Exposure to Pesticides. Frontiers in Oncology, v. 12, Article 904813, p. 1 - 13, July 2022.
2234-943X
10.3389/fonc.2022.904813
url https://www.arca.fiocruz.br/handle/icict/56228
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/56228/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/56228/2/Cibele_BOnvicino_etal_2022.pdf
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repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv repositorio.arca@fiocruz.br
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