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 pharmacogenomics, 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 polymorphism 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 restrictions. 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 “variation” or “variant”) and (“dihydropirymidines dehydrogenase” or “DPYD” or “DPD”) and (“colorectal 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 polymorphisms were correlated with the incidence of marrow suppression, gastrointestinal reaction and hand-foot 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 therapy, and to make treatment decisions for their patients maximizing benefit and minimizing toxicity.
To cite this article
Impact of DPYD variants in Fluoropyrimidine based-therapy: the state of the art
WCRJ 2014; 1 (3): e279
Published online: 01 Oct 2014
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