Polymorphism of cytochrome P450 (CYP) genes and response to chemiotherapy in patients with colorectal cancer (CRC)

Risultato della ricerca: Otherpeer review


Background: Genes coding for the cytochrome P450 (CYP) enzymesystem implied in antineoplastic drug metabolism pathways are highlypolymorphic. This may influence both carcinogen metabolism and drugpharmacodynamics modifying their therapeutic efficacy and side effects.Methods: We investigated the influence of genetic polymorphisms of CYPenzymes: rs1799853 (CYP2C9), rs35742686 (CYP2D), rs5030655(CYP2D6/3), rs2740574 (CYP3A4/1) rs776746 (CYP3A5) on theresponse of chemotherapy and clinical outcomes, in a group of 56patients affected by sporadic CRC, treated with the standard protocols. Atotal of 44 patients were in complete remission after treatment, 12 hadpersistence of the disease. Polymorphisms were typed using acompetitive allele specific PCR assay (KASPar), developed byKBioscience. Statistical were analyzed using the χ2 test with Yatescorrection and Fisher's Exact Test. Significance was defined as p values<0.05.Results: No significant genetic contribute was observed for 4 of the 5SNPs tested. A significant different genetic distribution between patients incomplete remission after treatment and those of symptomatic patients wasobserved for the polymorphism C→T (rs1799853) responsible of anArg144Cys change in CYP2C9 and associated with reduced enzymeactivity (p=0.031, O.R.= 4.760, 95% C. I.: 1.237 to 18.311).Conclusions: These results suggest that rs1799853 is a functionalyrelevant SNP of CYP2C9 that may influence the efficacy of therapy. Thus,pharmacogenetic biomarkers have the potential of optimizingchemotherapy for individual patients
Lingua originaleEnglish
Numero di pagine1
Stato di pubblicazionePublished - 2014


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