p.G12C KRAS mutation prevalence in non-small cell lung cancer: Contribution from interregional variability and population substructures among Hispanics

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dc.contributor.authorRuíz-Patiño, Alejandro
dc.contributor.authorRodríguez, July
dc.contributor.authorÁvila, Jenny
dc.contributor.authorArchila, Pilar
dc.contributor.authorCarranza, Hernán
dc.contributor.authorVargas, Carlos Alberto
dc.contributor.authorOtero, Jorge Miguel
dc.contributor.authorArrieta, Oscar
dc.contributor.authorZatarain-Barrón, Lucia
dc.contributor.authorSotelo, Carolina
dc.contributor.authorOrdoñez, Camila
dc.contributor.orcidCardona, Andrés Felipe [https://orcid.org/0000-0003-3525-4126]
dc.date.accessioned2022-02-09T22:07:28Z
dc.date.available2022-02-09T22:07:28Z
dc.date.issued2022-01
dc.description.abstractAntecedentes: El exón 2 de KRAS p. La mutación G12C en pacientes con adenocarcinoma de pulmón ha ido aumentando en relevancia debido al desarrollo y la eficacia de nuevos medicamentos de tratamiento. Estudios en diferentes poblaciones indican que la variabilidad regional entre etnias y ascendencias podría desempeñar un papel fundamental en el desarrollo de esta alteración molecular dentro del cáncer de pulmón. Results: Included were 979 patients with a national mean frequency for the KRAS exon 2 p.G12C mutation of 7.97% (95%CI 6.27-9.66%). Variation between regions was also identified with Antioquia reaching a positivity value of 12.7% (95%CI 9.1-16.3%) in contrast to other regions such as Bogota DC (Capital region) with 5.4% (2.7-8.2%) and Bolivar with 2.4% (95%CI 0-7.2%) (p-value = 0.00262). Furthermore, Short tandem repeat population substructures were found for eight markers that strongly yielded association with KRAS exon 2 p.G12C frequency reaching an adjusted R2 of 0.945 and a p-value of < 0.0001. Conclusions: Widespread identification of KRAS exon 2 p.G12C mutations, especially in cases where NGS is not easily achieved is feasible at a population based level that can characterize regional and national patterns of mutation status. Furthermore, this type of mutation prevalence follows a population substructure pattern that can be easily determined by population and ancestral markers such as STR.spa
dc.description.abstractenglishBackground: The KRAS exon 2 p. G12C mutation in patients with lung adenocarcinoma has been increasing in relevance due to the development and effectiveness of new treatment medications. Studies around different populations indicate that regional variability between ethnic groups and ancestries could play an essential role in developing this molecular alteration within lung cancer. Methods: In a prospective and retrospective cohort study on samples from lung adenocarcinoma from 1000 patients from different administrative regions in Colombia were tested for the KRAS p.G12C mutation. An analysis of STR populations markers was conducted to identify substructure contributions to mutation prevalence. Results: Included were 979 patients with a national mean frequency for the KRAS exon 2 p.G12C mutation of 7.97% (95%CI 6.27-9.66%). Variation between regions was also identified with Antioquia reaching a positivity value of 12.7% (95%CI 9.1-16.3%) in contrast to other regions such as Bogota DC (Capital region) with 5.4% (2.7-8.2%) and Bolivar with 2.4% (95%CI 0-7.2%) (p-value = 0.00262). Furthermore, Short tandem repeat population substructures were found for eight markers that strongly yielded association with KRAS exon 2 p.G12C frequency reaching an adjusted R2 of 0.945 and a p-value of < 0.0001. Conclusions: Widespread identification of KRAS exon 2 p.G12C mutations, especially in cases where NGS is not easily achieved is feasible at a population based level that can characterize regional and national patterns of mutation status. Furthermore, this type of mutation prevalence follows a population substructure pattern that can be easily determined by population and ancestral markers such as STR.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1016/j.tranon.2021.101276
dc.identifier.instnameinstname:Universidad El Bosquespa
dc.identifier.issn1936-5233
dc.identifier.reponamereponame:Repositorio Institucional Universidad El Bosquespa
dc.identifier.repourlrepourl:https://repositorio.unbosque.edu.co
dc.identifier.urihttps://hdl.handle.net/20.500.12495/6801
dc.language.isoeng
dc.publisherNeoplasia Press, Inc.spa
dc.publisher.journalTranslational Oncologyspa
dc.relation.ispartofseriesTranslational Oncology, 1936-5233, Vol 15, Num 1, 2022spa
dc.relation.urihttps://linkinghub.elsevier.com/retrieve/pii/S1936-5233(21)00267-9
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.accessrightshttps://purl.org/coar/access_right/c_abf2
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.rights.accessrightsAcceso abierto
dc.rights.localAcceso abiertospa
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectEpidemiología molecularspa
dc.subjectCáncer de pulmón de células no pequeñasspa
dc.subjectMarcadores de poblaciónspa
dc.subject.keywordsKRASspa
dc.subject.keywordsMolecular epidemiologyspa
dc.subject.keywordsNon small cell lung cancerspa
dc.subject.keywordsPopulation markersspa
dc.titlep.G12C KRAS mutation prevalence in non-small cell lung cancer: Contribution from interregional variability and population substructures among Hispanicsspa
dc.title.translatedp.G12C KRAS mutation prevalence in non-small cell lung cancer: Contribution from interregional variability and population substructures among Hispanicsspa
dc.type.coarhttps://purl.org/coar/resource_type/c_6501
dc.type.coarversionhttps://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.driverinfo:eu-repo/semantics/article
dc.type.hasversioninfo:eu-repo/semantics/publishedVersion
dc.type.localArtículo de revista

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