A case-control study of a combination of single nucleotide polymorphisms and clinical parameters to predict clinically relevant toxicity associated with fluoropyrimidine and platinum-based chemotherapy in gastric cancer

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dc.article.number1030
dc.contributor.authorCordova-Delgado, Miguel
dc.contributor.authorBravo Castillo, María Loreto
dc.contributor.authorCumsille, Elisa
dc.contributor.authorHill Machado, Charlotte Nicole
dc.contributor.authorPinto, Mauricio P.
dc.contributor.authorMiquel P., Juan Francisco
dc.contributor.authorRodríguez-Fernández, María
dc.contributor.authorCorvalán R., Alejandro
dc.contributor.authorGarrido S., Marcelo
dc.contributor.authorOwen, Gareth Ivor
dc.date.accessioned2021-09-29T14:56:41Z
dc.date.available2021-09-29T14:56:41Z
dc.date.issued2021
dc.date.updated2021-09-19T00:02:11Z
dc.description.abstractBackground: Fluoropyrimidine plus platinum chemotherapy remains the standard first line treatment for gastric cancer (GC). Guidelines exist for the clinical interpretation of four DPYD genotypes related to severe fluoropyrimidine toxicity within European populations. However, the frequency of these single nucleotide polymorphisms (SNPs) in the Latin American population is low (< 0.7%). No guidelines have been development for platinum. Herein, we present association between clinical factors and common SNPs in the development of grade 3–4 toxicity. Methods: Retrospectively, 224 clinical records of GC patient were screened, of which 93 patients were incorporated into the study. Eleven SNPs with minor allelic frequency above 5% in GSTP1, ERCC2, ERCC1, TP53, UMPS, SHMT1, MTHFR, ABCC2 and DPYD were assessed. Association between patient clinical characteristics and toxicity was estimated using logistic regression models and classification algorithms. Results; Reported grade ≤ 2 and 3–4 toxicities were 64.6% (61/93) and 34.4% (32/93) respectively. Selected DPYD SNPs were associated with higher toxicity (rs1801265; OR = 4.20; 95% CI = 1.70–10.95, p = 0.002), while others displayed a trend towards lower toxicity (rs1801159; OR = 0.45; 95% CI = 0.19–1.08; p = 0.071). Combination of paired SNPs demonstrated significant associations in DPYD (rs1801265), UMPS (rs1801019), ABCC2 (rs717620) and SHMT1 (rs1979277). Using multivariate logistic regression that combined age, sex, peri-operative chemotherapy, 5-FU regimen, the binary combination of the SNPs DPYD (rs1801265) + ABCC2 (rs717620), and DPYD (rs1801159) displayed the best predictive performance. A nomogram was constructed to assess the risk of developing overall toxicity. Conclusion: Pending further validation, this model could predict chemotherapy associated toxicity and improve GC patient quality of life.
dc.format.extent18 páginas
dc.fuente.origenAutoarchivo
dc.identifier.citationBMC Cancer. 2021 Sep 16;21(1):1030
dc.identifier.doi10.1186/s12885-021-08745-0
dc.identifier.urihttps://doi.org/10.1186/s12885-021-08745-0
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/62516
dc.information.autorucFacultad de Ciencias Biológicas ; Cordova-Delgado, Miguel ; 0000-0002-3132-226X ; 0
dc.information.autorucFacultad de Ciencias Biológicas ; Bravo Castillo, María Loreto ; 0000-0003-1231-400X ; 125561
dc.information.autorucFacultad de Ciencias Biológicas ; Cumsille, Elisa ; S/I ; 215446
dc.information.autorucFacultad de Ciencias Biológicas ; Hill Machado, Charlotte Nicole ; S/I ; 186997
dc.information.autorucFacultad de Ciencias Biológicas ; Pinto, Mauricio P. ; 0000-0003-2484-8033 ; 0
dc.information.autorucEscuela de Medicina ; Miquel P., Juan Francisco ; 0000-0002-0526-4377 ; 72216
dc.information.autorucEscuela de Ingeniería ; Rodríguez-Fernández, María ; 0000-0003-1966-2920 ; 1031920
dc.information.autorucEscuela de Medicina ; Corvalán R., Alejandro ; 0000-0001-5492-3853 ; 63885
dc.information.autorucEscuela de Medicina ; Garrido Salvo, Marcelo Adán ; 0000-0001-8905-8986 ; 7260
dc.information.autorucEscuela de Medicina ; Owen, Gareth Ivor ; 0000-0003-3807-6054 ; 1000459
dc.language.isoen
dc.nota.accesoContenido completo
dc.pagina.final18
dc.pagina.inicio1
dc.revistaBMC Cancer
dc.rightsacceso abierto
dc.rights.holderThe Author(s)
dc.subjectPredictive modelses_ES
dc.subjectSingle nucleotide polymorphismes_ES
dc.subjectChemotherapy toxicityes_ES
dc.subjectFluoropyrimidineses_ES
dc.subjectPlatinumses_ES
dc.subject.ddc615.58
dc.subject.deweyMedicina y saludes_ES
dc.titleA case-control study of a combination of single nucleotide polymorphisms and clinical parameters to predict clinically relevant toxicity associated with fluoropyrimidine and platinum-based chemotherapy in gastric canceres_ES
dc.typeartículo
dc.volumen21
sipa.codpersvinculados125561
sipa.codpersvinculados215446
sipa.codpersvinculados186997
sipa.codpersvinculados72216
sipa.codpersvinculados1031920
sipa.codpersvinculados63885
sipa.codpersvinculados7260
sipa.codpersvinculados1000459
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