15357163mct131109-sup-124917_1_supp_2477642_n5rm30.pptx (67.71 kB)
Data Supplement from Pharmacogenetic Predictors of Outcome in Patients with Stage II and III Colon Cancer Treated with Oxaliplatin and Fluoropyrimidine-Based Adjuvant Chemotherapy
figureposted on 2023-04-03, 14:26 authored by Ana Custodio, Juan Moreno-Rubio, Jorge Aparicio, Javier Gallego-Plazas, Ricardo Yaya, Joan Maurel, Nuria Rodríguez-Salas, Emilio Burgos, David Ramos, Ana Calatrava, Encarna Andrada, Esther Díaz-López, Antonio Sánchez, Rosario Madero, Paloma Cejas, Jaime Feliu
Supplementary Table S3. Cox regression multivariate analysis for disease free survival (DFS) in stage III colon cancer patients.
ARTICLE ABSTRACTIdentifying molecular markers for tumor recurrence is critical in successfully selecting patients with colon cancer who are more likely to benefit from adjuvant chemotherapy. We investigated the effect of single-nucleotide polymorphisms (SNP) within genes involved in oxaliplatin and fluoropyrimidines metabolism, DNA repair mechanisms, drug transport, or angiogenesis pathways on outcome for patients with stage II and III colon cancer treated with adjuvant chemotherapy. Genomic DNA was extracted from formalin-fixed paraffin-embedded samples of 202 patients with stage II and III colon cancer receiving oxaliplatin-based adjuvant chemotherapy from January 2004 to December 2009. Genotyping was performed for 67 SNPs in 32 genes using the MassARRAY (SEQUENOM) technology. Our results were validated in an independent cohort of 177 patients treated with the same chemotherapy regimens. The combination of the selectin E (SELE) rs3917412 G>A G/G and the methylentetrahydrofolate reductase (MTHFR) rs1801133 T/T genotypes was associated with a significantly increased risk for recurrence in both the training [RR = 4.103; 95% confidence interval (CI), 1.803–9.334; P = 0.001] and the validation cohorts (RR = 3.567; 95% CI, 1.253–10.151; P = 0.017) in the multiple regression analysis considering the stage, lymphovascular invasion, and bowel perforation as covariates. The combined analysis of these polymorphisms was also significantly associated with overall survival in both cohorts (RR = 3.388; 95% CI, 0.988–11.623; P = 0.052, and RR = 3.929; 95% CI, 1.144–13.485; P = 0.020, respectively). Our findings suggest that the SELE rs3917412 and MTHFR rs1801133 SNPs could serve as pharmacogenetic predictors of tumor recurrence in patients with early-stage colon cancer treated with oxaliplatin-based adjuvant chemotherapy, thus allowing personalized selection of treatment to optimize clinical outcomes. Mol Cancer Ther; 13(9); 2226–37. ©2014 AACR.
CarcinogenesisAnimal models of carcinogenesisCell CycleSignal transduction pathwaysClinical Trial ResultsEndocrine-Related CancersEndogenous Risk FactorsGene polymorphismsGastrointestinal CancersColorectal cancerStomach cancerGenetics Of Cancer Risk & OutcomeCell growth and development polymorphismsPreclinical ModelsAnimal models of cancer