Beyond tobacco: genomic disparities in lung cancer between smokers and never-smokers

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dc.article.number951
dc.catalogadoryvc
dc.contributor.authorGarrido, Javiera
dc.contributor.authorBernal, Yanara
dc.contributor.authorGonzález, Evelin
dc.contributor.authorBlanco, Alejandro
dc.contributor.authorSepúlveda-Hermosilla, Gonzalo
dc.contributor.authorFreire, Matías
dc.contributor.authorOróstica, Karen
dc.contributor.authorRivas, Solange
dc.contributor.authorMarcelain, Katherine
dc.contributor.authorOwen, Gareth Ivor
dc.contributor.authorIbáñez Cáceres, Carolina
dc.contributor.authorCorvalán Rodríguez, Alejandro
dc.contributor.authorGarrido, Marcelo
dc.contributor.authorAssar, Rodrigo
dc.contributor.authorLizana, Rodrigo
dc.contributor.authorCáceres-Molina, Javier
dc.contributor.authorAmpuero, Diego
dc.contributor.authorRamos, Liliana
dc.contributor.authorPérez, Paola
dc.contributor.authorAren, Osvaldo
dc.contributor.authorChernilo, Sara
dc.contributor.authorFernández, Cristina
dc.contributor.authorSpencer, María L.
dc.contributor.authorAguila, Jacqueline F.
dc.contributor.authorDossetto, Giuliano B.
dc.contributor.authorOlea, Mónica A.
dc.contributor.authorRasse, Germán
dc.contributor.authorSánchez, Carolina
dc.contributor.authorAmorim, Maria Galli de
dc.contributor.authorBartelli, Thais F.
dc.contributor.authorNunes, Diana N.
dc.contributor.authorDias-Neto, Emmanuel
dc.contributor.authorFreitas, Helano C.
dc.contributor.authorArmisén, Ricardo
dc.date.accessioned2024-08-06T23:23:03Z
dc.date.available2024-08-06T23:23:03Z
dc.date.issued2024
dc.date.updated2024-08-04T00:05:15Z
dc.description.abstractTobacco use is one of the main risk factors for Lung Cancer (LC) development. However, about 10–20% of those diagnosed with the disease are never-smokers. For Non-Small Cell Lung Cancer (NSCLC) there are clear differences in both the clinical presentation and the tumor genomic profiles between smokers and never-smokers. For example, the Lung Adenocarcinoma (LUAD) histological subtype in never-smokers is predominately found in young women of European, North American, and Asian descent. While the clinical presentation and tumor genomic profiles of smokers have been widely examined, never-smokers are usually underrepresented, especially those of a Latin American (LA) background. In this work, we characterize, for the first time, the difference in the genomic profiles between smokers and never-smokers LC patients from Chile. Methods We conduct a comparison by smoking status in the frequencies of genomic alterations (GAs) including somatic mutations and structural variants (fusions) in a total of 10 clinically relevant genes, including the eight most common actionable genes for LC (EGFR, KRAS, ALK, MET, BRAF, RET, ERBB2, and ROS1) and two established driver genes for malignancies other than LC (PIK3CA and MAP2K1). Study participants were grouped as either smokers (current and former, n = 473) or never-smokers (n = 200) according to self-report tobacco use at enrollment. Results Our findings indicate a higher overall GA frequency for never-smokers compared to smokers (58 vs. 45.7, p-value < 0.01) with the genes EGFR, KRAS, and PIK3CA displaying the highest prevalence while ERBB2, RET, and ROS1 the lowest. Never-smokers present higher frequencies in seven out of the 10 genes; however, smokers harbor a more complex genomic profile. The clearest differences between groups are seen for EGFR (15.6 vs. 21.5, p-value: < 0.01), PIK3CA (6.8 vs 9.5) and ALK (3.2 vs 7.5) in favor of never-smokers, and KRAS (16.3 vs. 11.5) and MAP2K1 (6.6 vs. 3.5) in favor of smokers. Alterations in these genes are comprised almost exclusively by somatic mutations in EGFR and mainly by fusions in ALK, and only by mutations in PIK3CA, KRAS and MAP2K1. Conclusions We found clear differences in the genomic landscape by smoking status in LUAD patients from Chile, with potential implications for clinical management in these limited-resource settings.
dc.description.funderCORFO International Center of Excellence Program #13CEE2-21602
dc.description.funderANID FONDECYT 3210455 & 1220586
dc.description.funderCONICYT-FONDAP 15130011
dc.description.funderANID-FONDAP 152220002
dc.description.funderANID PROGRAMA ICM/ICN2021_045
dc.fechaingreso.objetodigital2024-08-04
dc.format.extent15 páginas
dc.fuente.origenBiomed Central
dc.identifier.citationBMC Cancer. 2024 Aug 03;24(1):951
dc.identifier.doi10.1186/s12885-024-12737-1
dc.identifier.issn1471-2407
dc.identifier.urihttps://doi.org/10.1186/s12885-024-12737-1
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/87309
dc.information.autorucFacultad de Ciencias Biológicas; Owen Gareth Ivor; 0000-0003-3807-6054; 1000459
dc.information.autorucEscuela de Medicina; Ibáñez Cáceres, Carolina; S/I; 146063
dc.information.autorucEscuela de Medicina; Corvalán Rodríguez, Alejandro; 0000-0001-5492-3853; 63885
dc.language.isoen
dc.nota.accesocontenido completo
dc.publisherSpringer Nature
dc.revistaBMC Cancer
dc.rightsacceso abierto
dc.rights.holderThe Author(s)
dc.rights.licenseBY-NC-ND Atribución-NoComercial-SinDerivadas Internacional 4.0
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectLung Adenocarcinoma
dc.subjectTobacco consumption
dc.subjectLatin American populations
dc.subjectEGFR mutation
dc.subjectCancer disparities
dc.subjectKRAS
dc.subjectMAP2K1
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleBeyond tobacco: genomic disparities in lung cancer between smokers and never-smokers
dc.typeartículo
dc.volumen24
sipa.codpersvinculados1000459
sipa.codpersvinculados146063
sipa.codpersvinculados63885
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