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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.    Supplementary Information  The online version contains supplementary material available at 10.1186/s12885-021-08745-0.

bmc cancer

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