IMPACT OF DPYD VARIANTS IN FLUOROPYRIMIDINE BASED-THERAPY: THE STATE OF THE ART

Absract ‐ Background: The 5-Fluorouracil (5-FU) is the backbone of different regimens for the treatment of several solid tumours. Unlikely, some patients develop gastrointestinal and hematologic toxicities when treated by the 5-FU, leading to the suspension of therapy. Current evidences of phar macogenomics, have reported several dihydropirymidines dehydrogenase (DPYD) polymorphisms associated to genes involved with fluoropyrimidine catabolism. Methods : Some adverse drug response due to the administration of 5-FU can be predicted through pharmacogenomics testing tools. This report reviews the recent findings on the polymor phism for DPYD genes that are involved in the metabolic degradation of 5-FU and its association with the toxic effect in patients. Literature searching in the web were based on the English language re strictions. We used the following keywords and MeSH terms in conjunction with a highly sensitive search strategy: (“genetic polymorphism” or “single nucleotide polymorphism” or “SNP” or “varia tion” or “variant”) and (“dihydropirymidines dehydrogenase” or “DPYD” or “DPD”) and (“colorec tal cancer” or “gastrointestinal carcinogenesis” or “colorectal tumor” or “colorectal carcinoma” or “large intestine cancer” or “large intestine carcinoma” or “large colon cancer”). Also, we will take in considerations the recent methods used to identify these genetic alterations. Conclusions: The present review suggests that DPYD IVS14+1, 496A>G and 2194G>A polymor phisms were correlated with the incidence of marrow suppression, gastrointestinal reaction and handfoot syndrome in colorectal cancer (CRC ) patients However, many clinicians acknowledge the importance of genetics in drug response and are favourable about using genetic tests to guide ther apy, and to make treatment decisions for their patients maximizing benefit and minimizing toxicity.