Dihydropirimidin dehydrogenase (DPD29) single nucleotide polymorphism but not ERCC1, XPD, cytidine deaminase (CD) or DPD543, predicts duration of response to cisplatin/5FU based chemotherapy in oropharyngeal carcinoma

Abstract

5547 Background: Single nucleotide polymorphisms (SNPs) correlate with response to chemotherapy. ERCC1 and XPD are DNA repair genes which SNPs predict response to cisplatin in non-small cell lung cancer. CD and DPD are intermediate pathways enzymes in the metabolism of the pirimidine analogues. We evaluated the presence of SNPs of these genes in patients (pts) with oropharyngeal carcinoma and its relationship with chemotherapy response. Methods: We analysed paraffin-embedded biopsies from 24 consecutive pts with locally advanced oropharyngeal carcinoma who received chemoradiotherapy based on platinum (Pt) and 5-fluorouracil (5FU) for SNPs of genes ERCC1 (Lys259Thr), XPD (Lys751Gln), CD intron (in an intronic region T/C), CD (Lys27Gln), DPD543 (Ile543Val) and DPD29 (Arg29Cys). The status of alleles (wild type or at least 1 polymorphism) was correlated with response rate (RR), time to progression (TTP) and overall survival (OS). Results: All 24 pts received Pt (n=24) or 5FU plus Pt (n=19). Overall RR was 75% (16/24) with a median TTP of 12 months (95% CI 6–18m) and a median OS of 32 months (95% CI 14–50m). The status of SNPs was classified as not available/wild type/heterozygous SNP/homozygous SNP, which frequencies were 5/16/3/0 in ERCC1; 2/8/12/2 in XPD; 2/2/10/10 in CD; 2/21/0/1 in CD intron; 1/18/5/0 in DPD543; and 1/15/7/1 in DPD29 respectively. Response rate in DPD29 was 70% for wild type vs 40% for polymorphism (p= 0.656). Only significant differences were seen in TTP between pts with wild type vs polymorphic DPD29 (p=0.037). No difference in survival was observed. Conclusions: SNPs of DPD29 predict duration of response to chemotherapy containing Pt-5FU in pts with oropharyngeal carcinoma. No significant financial relationships to disclose.