Determination Of Dihydropyrimidine Dehydrogenase (Dpyd) Gene Single-Nucleotide Polymorphism (Snp) In Mexican Patients With Locally Advanced Esophageal Carcinoma.

93 Background: Fluoropyrimidines as 5-fluorouracil (5-FU) and its prodrug capecitabine are chemotherapeutic drugs commonly used in the treatment of gastrointestinal cancer. Patients with deficiency of dihydropyrimidine dehydrogenase enzyme (DPD), which interfere with the pyrimidine metabolism, could be at risk toxicity (mild, severe or lethal) because 80-90% of the administered 5-FU is catabolized by DPD. Methods: Retrospectively, we analyzed the initial paraffin embedded tissue block of 72 Mexican patients with locally advanced esophageal cancer, DPD activity was evaluated through the detection of the seven most relevant DPYD SNPs (IVS14 + 1G>A; 85T>C/85T>T; 2657G>A; 2921A>T; 1679T>G; 2846A>T; and 496A>G). Results: We found that 20.83% (15/72) of our patients had three different polymorphisms: 9.72% (7/72) were positive for SNP 496A>G in heterozygous patients and 4.16% (3/72) in homozygous patients; 4.16% (3/72) were positive for SNP 2657G>A in heterozygous patients; 2.77% (2/72) were positive for SNPs 85T>C and 85T>T in heterozygous patients. The rest of patients 79.10% (57/72) were negative to these SNPs. Conclusions: This is the first study in Mexican population, determining DPYD SNPs. We found that frequency of SNP 85T>C and 85T>T is similar as Oriental race (2-3%), but contrast with Caucasians (0.19%). The SNP 2657G>A whose allelic frequency is unknown, in Mexicans is about 4%; meanwhile, for SNP 496A>G which Caucasian prevalence was reported 0.8%, in our Mexican sample was very high (14%). None of our patients even those with toxicity grade 3-4, were positive to the SNP associated to high toxicity (IVS14 + 1G>A). Because of this heterogeneity, know we are sequencing the complete gen.