Incidence of hereditary gastric cancer may be much higher than reported
Autor(a) principal: | |
---|---|
Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRN |
Texto Completo: | https://repositorio.ufrn.br/handle/123456789/51232 |
Resumo: | Hereditary gastric cancers (HGCs) are supposed to be rare and difficult to identify. Nonetheless, many cases of young patients with gastric cancer (GC) fulfill the clinical criteria for considering this diagnosis but do not present the defined pathogenic mutations necessary to meet a formal diagnosis of HGC. Moreover, GC in young people is a challenging medical situation due to the usual aggressiveness of such cases and the potential risk for their relatives when related to a germline variant. Aiming to identify additional germline alterations that might contribute to the early onset of GC, a complete exome sequence of blood samples from 95 GC patients under 50 and 94 blood samples from non-cancer patients was performed and compared in this study. The number of identified germline mutations in GC patients was found to be much higher than that from individuals without a cancer diagnosis. Specifically, the number of high functional impact mutations, including those affecting genes involved in medical diseases, cancer hallmark genes, and DNA replication and repair processes, was much higher, strengthening the hypothesis of the potential causal role of such mutations in hereditary cancers. Conversely, classically related HGC mutations were not found and the number of mutations in genes in the CDH1 pathway was not found to be relevant among the young GC patients, reinforcing the hypothesis that existing alternative germline contributions favor the early onset of GC. The LILRB1 gene variants, absent in the world's cancer datasets but present in high frequencies among the studied GC patients, may represent essential cancer variants specific to the Amerindian ancestry's contributions. Identifying non-reported GC variants, potentially originating from under-studied populations, may pave the way for additional discoveries and translations to clinical interventions for GC management. The newly proposed approaches may reduce the discrepancy between clinically suspected and molecularly proven hereditary GC and shed light on similar inconsistencies among other cancer types. Additionally, the results of this study may support the development of new blood tests for evaluating cancer risk that can be used in clinical practice, helping physicians make decisions about strategies for surveillance and risk-reduction interventions |
id |
UFRN_c92afcfb1ed503a6948f6f5ee51ce57d |
---|---|
oai_identifier_str |
oai:https://repositorio.ufrn.br:123456789/51232 |
network_acronym_str |
UFRN |
network_name_str |
Repositório Institucional da UFRN |
repository_id_str |
|
spelling |
Assumpção, Paula Baraúna deAssumpção, Paulo Pimentel deMoreira, Fabiano CordeiroSantos, Andrea Kely Campos Ribeiro dosVidal, Amanda FerreiraMagalhães, LeandroKhayat, André SalimSantos, André Mauricio Ribeiro dosCavalcante, Giovanna ChavesPereira, Adenilson LeãoMedeiros, Inácio GomesSouza, Sandro José deBurbano, Rommel Mario RodríguezSouza, Jorge Estefano Santana deSantos, Sidney Emanuel Batista dos2023-02-08T11:55:56Z2023-02-08T11:55:56Z2022-12ASSUMPÇÃO, Paula Baraúna de; ASSUMPÇÃO, Paulo Pimentel de; MOREIRA, Fabiano Cordeiro; RIBEIRO-DOS-SANTOS, Ândrea; VIDAL, Amanda F.; MAGALHÃES, Leandro; KHAYAT, André Salim; RIBEIRO-DOS-SANTOS, André Maurício; CAVALCANTE, Giovanna C.; PEREIRA, Adenilson Leão; MEDEIROS, Inácio; SOUZA, Sandro José de; BURBANO, Rommel Mario Rodríguez; SOUZA, Jorge Estefano Santana de; SANTOS, Sidney Emanuel Batista dos. Incidence of Hereditary Gastric Cancer May Be Much Higher than Reported. Cancers, [S. l.], v. 14, n. 24, p. 6125, dez. 2022. Doi: http://dx.doi.org/10.3390/cancers14246125. Disponível em: https://www.mdpi.com/2072-6694/14/24/6125. Acesso em: 07 fev. 2023.https://repositorio.ufrn.br/handle/123456789/5123210.3390/cancers14246125MDPI AGAttribution 3.0 Brazilhttp://creativecommons.org/licenses/by/3.0/br/info:eu-repo/semantics/openAccessHereditary gastric cancerStomach neoplasmsGerm-line mutationEpidemiology - Cancer - AncestryWhole exome sequencingIncidence of hereditary gastric cancer may be much higher than reportedinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleHereditary gastric cancers (HGCs) are supposed to be rare and difficult to identify. Nonetheless, many cases of young patients with gastric cancer (GC) fulfill the clinical criteria for considering this diagnosis but do not present the defined pathogenic mutations necessary to meet a formal diagnosis of HGC. Moreover, GC in young people is a challenging medical situation due to the usual aggressiveness of such cases and the potential risk for their relatives when related to a germline variant. Aiming to identify additional germline alterations that might contribute to the early onset of GC, a complete exome sequence of blood samples from 95 GC patients under 50 and 94 blood samples from non-cancer patients was performed and compared in this study. The number of identified germline mutations in GC patients was found to be much higher than that from individuals without a cancer diagnosis. Specifically, the number of high functional impact mutations, including those affecting genes involved in medical diseases, cancer hallmark genes, and DNA replication and repair processes, was much higher, strengthening the hypothesis of the potential causal role of such mutations in hereditary cancers. Conversely, classically related HGC mutations were not found and the number of mutations in genes in the CDH1 pathway was not found to be relevant among the young GC patients, reinforcing the hypothesis that existing alternative germline contributions favor the early onset of GC. The LILRB1 gene variants, absent in the world's cancer datasets but present in high frequencies among the studied GC patients, may represent essential cancer variants specific to the Amerindian ancestry's contributions. Identifying non-reported GC variants, potentially originating from under-studied populations, may pave the way for additional discoveries and translations to clinical interventions for GC management. The newly proposed approaches may reduce the discrepancy between clinically suspected and molecularly proven hereditary GC and shed light on similar inconsistencies among other cancer types. Additionally, the results of this study may support the development of new blood tests for evaluating cancer risk that can be used in clinical practice, helping physicians make decisions about strategies for surveillance and risk-reduction interventionsengreponame:Repositório Institucional da UFRNinstname:Universidade Federal do Rio Grande do Norte (UFRN)instacron:UFRNCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8914https://repositorio.ufrn.br/bitstream/123456789/51232/2/license_rdf4d2950bda3d176f570a9f8b328dfbbefMD52LICENSElicense.txtlicense.txttext/plain; charset=utf-81484https://repositorio.ufrn.br/bitstream/123456789/51232/3/license.txte9597aa2854d128fd968be5edc8a28d9MD53ORIGINALIncidenceHereditaryGastric_Souza_2022.pdfIncidenceHereditaryGastric_Souza_2022.pdfIncidenceHereditaryGastric_Souza_2022application/pdf4441226https://repositorio.ufrn.br/bitstream/123456789/51232/1/IncidenceHereditaryGastric_Souza_2022.pdf5cf74b02bee4422bc5ab9709bcc4d3e1MD51123456789/512322023-02-08 08:55:56.751oai:https://repositorio.ufrn.br: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Repositório de PublicaçõesPUBhttp://repositorio.ufrn.br/oai/opendoar:2023-02-08T11:55:56Repositório Institucional da UFRN - Universidade Federal do Rio Grande do Norte (UFRN)false |
dc.title.pt_BR.fl_str_mv |
Incidence of hereditary gastric cancer may be much higher than reported |
title |
Incidence of hereditary gastric cancer may be much higher than reported |
spellingShingle |
Incidence of hereditary gastric cancer may be much higher than reported Assumpção, Paula Baraúna de Hereditary gastric cancer Stomach neoplasms Germ-line mutation Epidemiology - Cancer - Ancestry Whole exome sequencing |
title_short |
Incidence of hereditary gastric cancer may be much higher than reported |
title_full |
Incidence of hereditary gastric cancer may be much higher than reported |
title_fullStr |
Incidence of hereditary gastric cancer may be much higher than reported |
title_full_unstemmed |
Incidence of hereditary gastric cancer may be much higher than reported |
title_sort |
Incidence of hereditary gastric cancer may be much higher than reported |
author |
Assumpção, Paula Baraúna de |
author_facet |
Assumpção, Paula Baraúna de Assumpção, Paulo Pimentel de Moreira, Fabiano Cordeiro Santos, Andrea Kely Campos Ribeiro dos Vidal, Amanda Ferreira Magalhães, Leandro Khayat, André Salim Santos, André Mauricio Ribeiro dos Cavalcante, Giovanna Chaves Pereira, Adenilson Leão Medeiros, Inácio Gomes Souza, Sandro José de Burbano, Rommel Mario Rodríguez Souza, Jorge Estefano Santana de Santos, Sidney Emanuel Batista dos |
author_role |
author |
author2 |
Assumpção, Paulo Pimentel de Moreira, Fabiano Cordeiro Santos, Andrea Kely Campos Ribeiro dos Vidal, Amanda Ferreira Magalhães, Leandro Khayat, André Salim Santos, André Mauricio Ribeiro dos Cavalcante, Giovanna Chaves Pereira, Adenilson Leão Medeiros, Inácio Gomes Souza, Sandro José de Burbano, Rommel Mario Rodríguez Souza, Jorge Estefano Santana de Santos, Sidney Emanuel Batista dos |
author2_role |
author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Assumpção, Paula Baraúna de Assumpção, Paulo Pimentel de Moreira, Fabiano Cordeiro Santos, Andrea Kely Campos Ribeiro dos Vidal, Amanda Ferreira Magalhães, Leandro Khayat, André Salim Santos, André Mauricio Ribeiro dos Cavalcante, Giovanna Chaves Pereira, Adenilson Leão Medeiros, Inácio Gomes Souza, Sandro José de Burbano, Rommel Mario Rodríguez Souza, Jorge Estefano Santana de Santos, Sidney Emanuel Batista dos |
dc.subject.por.fl_str_mv |
Hereditary gastric cancer Stomach neoplasms Germ-line mutation Epidemiology - Cancer - Ancestry Whole exome sequencing |
topic |
Hereditary gastric cancer Stomach neoplasms Germ-line mutation Epidemiology - Cancer - Ancestry Whole exome sequencing |
description |
Hereditary gastric cancers (HGCs) are supposed to be rare and difficult to identify. Nonetheless, many cases of young patients with gastric cancer (GC) fulfill the clinical criteria for considering this diagnosis but do not present the defined pathogenic mutations necessary to meet a formal diagnosis of HGC. Moreover, GC in young people is a challenging medical situation due to the usual aggressiveness of such cases and the potential risk for their relatives when related to a germline variant. Aiming to identify additional germline alterations that might contribute to the early onset of GC, a complete exome sequence of blood samples from 95 GC patients under 50 and 94 blood samples from non-cancer patients was performed and compared in this study. The number of identified germline mutations in GC patients was found to be much higher than that from individuals without a cancer diagnosis. Specifically, the number of high functional impact mutations, including those affecting genes involved in medical diseases, cancer hallmark genes, and DNA replication and repair processes, was much higher, strengthening the hypothesis of the potential causal role of such mutations in hereditary cancers. Conversely, classically related HGC mutations were not found and the number of mutations in genes in the CDH1 pathway was not found to be relevant among the young GC patients, reinforcing the hypothesis that existing alternative germline contributions favor the early onset of GC. The LILRB1 gene variants, absent in the world's cancer datasets but present in high frequencies among the studied GC patients, may represent essential cancer variants specific to the Amerindian ancestry's contributions. Identifying non-reported GC variants, potentially originating from under-studied populations, may pave the way for additional discoveries and translations to clinical interventions for GC management. The newly proposed approaches may reduce the discrepancy between clinically suspected and molecularly proven hereditary GC and shed light on similar inconsistencies among other cancer types. Additionally, the results of this study may support the development of new blood tests for evaluating cancer risk that can be used in clinical practice, helping physicians make decisions about strategies for surveillance and risk-reduction interventions |
publishDate |
2022 |
dc.date.issued.fl_str_mv |
2022-12 |
dc.date.accessioned.fl_str_mv |
2023-02-08T11:55:56Z |
dc.date.available.fl_str_mv |
2023-02-08T11:55:56Z |
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 |
ASSUMPÇÃO, Paula Baraúna de; ASSUMPÇÃO, Paulo Pimentel de; MOREIRA, Fabiano Cordeiro; RIBEIRO-DOS-SANTOS, Ândrea; VIDAL, Amanda F.; MAGALHÃES, Leandro; KHAYAT, André Salim; RIBEIRO-DOS-SANTOS, André Maurício; CAVALCANTE, Giovanna C.; PEREIRA, Adenilson Leão; MEDEIROS, Inácio; SOUZA, Sandro José de; BURBANO, Rommel Mario Rodríguez; SOUZA, Jorge Estefano Santana de; SANTOS, Sidney Emanuel Batista dos. Incidence of Hereditary Gastric Cancer May Be Much Higher than Reported. Cancers, [S. l.], v. 14, n. 24, p. 6125, dez. 2022. Doi: http://dx.doi.org/10.3390/cancers14246125. Disponível em: https://www.mdpi.com/2072-6694/14/24/6125. Acesso em: 07 fev. 2023. |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufrn.br/handle/123456789/51232 |
dc.identifier.doi.none.fl_str_mv |
10.3390/cancers14246125 |
identifier_str_mv |
ASSUMPÇÃO, Paula Baraúna de; ASSUMPÇÃO, Paulo Pimentel de; MOREIRA, Fabiano Cordeiro; RIBEIRO-DOS-SANTOS, Ândrea; VIDAL, Amanda F.; MAGALHÃES, Leandro; KHAYAT, André Salim; RIBEIRO-DOS-SANTOS, André Maurício; CAVALCANTE, Giovanna C.; PEREIRA, Adenilson Leão; MEDEIROS, Inácio; SOUZA, Sandro José de; BURBANO, Rommel Mario Rodríguez; SOUZA, Jorge Estefano Santana de; SANTOS, Sidney Emanuel Batista dos. Incidence of Hereditary Gastric Cancer May Be Much Higher than Reported. Cancers, [S. l.], v. 14, n. 24, p. 6125, dez. 2022. Doi: http://dx.doi.org/10.3390/cancers14246125. Disponível em: https://www.mdpi.com/2072-6694/14/24/6125. Acesso em: 07 fev. 2023. 10.3390/cancers14246125 |
url |
https://repositorio.ufrn.br/handle/123456789/51232 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
Attribution 3.0 Brazil http://creativecommons.org/licenses/by/3.0/br/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution 3.0 Brazil http://creativecommons.org/licenses/by/3.0/br/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
MDPI AG |
publisher.none.fl_str_mv |
MDPI AG |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFRN instname:Universidade Federal do Rio Grande do Norte (UFRN) instacron:UFRN |
instname_str |
Universidade Federal do Rio Grande do Norte (UFRN) |
instacron_str |
UFRN |
institution |
UFRN |
reponame_str |
Repositório Institucional da UFRN |
collection |
Repositório Institucional da UFRN |
bitstream.url.fl_str_mv |
https://repositorio.ufrn.br/bitstream/123456789/51232/2/license_rdf https://repositorio.ufrn.br/bitstream/123456789/51232/3/license.txt https://repositorio.ufrn.br/bitstream/123456789/51232/1/IncidenceHereditaryGastric_Souza_2022.pdf |
bitstream.checksum.fl_str_mv |
4d2950bda3d176f570a9f8b328dfbbef e9597aa2854d128fd968be5edc8a28d9 5cf74b02bee4422bc5ab9709bcc4d3e1 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional da UFRN - Universidade Federal do Rio Grande do Norte (UFRN) |
repository.mail.fl_str_mv |
|
_version_ |
1802117690143277056 |