engleski

DPYD polymorphism c.496A>G and risk of severe adverse drug reactions in cancer patients treated with fluoropyrimidine-based protocols

Patients with reduced dihydropyrimidine dehydrogenase (DPD) activity are at increased risk of severe fluoropyrimidine (FP)- related adverse events (AE). Several guidelines recommend FP dosing based on genotyping of four clinically relevant DPYD variants to predict DPD activity. We investigated the relationship between three further DPYD polymorphisms and the risk of severe FP-related AES. Study involved FP-treated cancer patients, genotyped for recommended DPYD variants 2A. *13 (c.1679T G). c.2846A T. c.1236G>A/HapB3. as well for c.496A G. c.2194G>A and c.85T>C (TaqMan real-time PCR) and for UGT1A1*28 (LightSNIP) if irinotecan was included. Patients were monitored for occurrence of grade 23 (National Cancer Institute Common Terminology Criteria) vs. grade 0-2 AES. For each tested polymorphisms, variant allele carriers were matched to respective wild type controls. Of 503 included patients (82.3% colorectal cancer), 283 (56.3%) developed grade 23 AES. Odds of grade 23 AEs were higher in c.496A G variant allele carriers (n=127) than in controls (n-376) [OR-5.20 (95%CI 1.88-14.3). Bayesian OR-5, 24 (95% Cri 3.06- 9.12)]. Odds tended to be higher in c.2194G>A variant allele carries (n=58) than in controls (n=432) (OR=1.88 (0.95-3.73), Bayesian OR=1.90 (1.03.3.56), c.8ST-G variant did not appear associated with grade 23 AES. DRYD C496ADG variant might need to be considered for inclusion in the DPYD genotyping pariel.

drugs reaction ; cancer ; fluoropyrimidine

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