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BMC Cancer ; 21(1): 1030, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34525956

RESUMO

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 (< 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.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Compostos de Platina/administração & dosagem , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Idoso , Capecitabina/efeitos adversos , Estudos de Casos e Controles , Intervalos de Confiança , Proteínas de Ligação a DNA/genética , Di-Hidrouracila Desidrogenase (NADP)/genética , Endonucleases/genética , Feminino , Fluoruracila/efeitos adversos , Frequência do Gene , Genes p53 , Genótipo , Glutationa S-Transferase pi/genética , Glicina Hidroximetiltransferase/genética , Humanos , Leucovorina/efeitos adversos , Modelos Logísticos , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Pessoa de Meia-Idade , Proteína 2 Associada à Farmacorresistência Múltipla , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Complexos Multienzimáticos/genética , Nomogramas , Razão de Chances , Compostos Organoplatínicos/efeitos adversos , Orotato Fosforribosiltransferase/genética , Orotidina-5'-Fosfato Descarboxilase/genética , Pirimidinas , Qualidade de Vida , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Proteína Grupo D do Xeroderma Pigmentoso/genética
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