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

Simple item page
dc.coverageDOI: 10.1186/s12885-021-08745-0
dc.creatorCordova-Delgado, Miguel
dc.creatorBravo, María Loreto
dc.creatorCumsille, Elisa
dc.creatorHill, Charlotte N.
dc.creatorMuñoz-Medel, Matías
dc.creatorPinto, Mauricio P.
dc.creatorRetamal, Ignacio N.
dc.creatorLavanderos, María A.
dc.creatorMiquel, Juan Francisco
dc.creatorRodriguez-Fernandez, Maria
dc.creatorLiao, Yuwei
dc.creatorLi, Zhiguang
dc.creatorCorvalán, Alejandro H.
dc.creatorArmisén, Ricardo
dc.creatorGarrido, Marcelo
dc.creatorQuiñones, Luis A.
dc.creatorOwen, Gareth I.
dc.date2021
dc.date.accessioned2025-11-18T19:48:24Z
dc.date.available2025-11-18T19:48:24Z
dc.description<p>Background: 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 (&lt; 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.</p>eng
dc.descriptionBackground: 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 (&lt; 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 lifespa
dc.identifierhttps://investigadores.uandes.cl/en/publications/843e607c-16c3-4558-822f-ceca3f187e0d
dc.identifier.urihttps://repositorio.uandes.cl/handle/uandes/55536
dc.languageeng
dc.rightsinfo:eu-repo/semantics/openAccess
dc.sourcevol.21 (2021) nr.1 p.1-18
dc.subjectChemotherapy toxicity
dc.subjectFluoropyrimidines
dc.subjectPlatinums
dc.subjectPredictive models
dc.subjectSingle nucleotide polymorphism
dc.subjectChemotherapy toxicity
dc.subjectFluoropyrimidines
dc.subjectPlatinums
dc.subjectPredictive models
dc.subjectSingle nucleotide polymorphism
dc.subjectSDG 3 - Good Health and Well-being
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 cancereng
dc.typeArticleeng
dc.typeArtículospa
Files
Collections
PURE