Relevance of CYP3A4*20, UGT1A1*37 and UGT1A1*28 variants in irinotecan-induced severe toxicity
Por:
Riera, P, Salazar, J, Virgili, AC, Tobena, M, Sebio, A, Gallano, P, Barnadas, A, Paez, D
Publicada:
1 jun 2018
Resumen:
Severe irinotecan-induced toxicity is associated with UGT1A1 polymorphisms. However, some patients develop side-effects despite harbouring a normal UGT1A1 genotype. As CYP3A4 is also an irinotecan-metabolizing enzyme, our study aimed to elucidate the influence of the CYP3A4*20 loss-of-function allele in the toxicity profile of these patients. Three-hundred and eight metastatic colorectal cancer patients treated with an irinotecan-containing chemotherapy were studied. The presence of CYP3A4*20, UGT1A1*37 and UGT1A1*28 alleles was tested. Associations between these genetic variants and toxicity were evaluated. UGT1A1*28 was significantly associated with severe diarrhoea, neutropenia and asthenia (P = 0.002, P = 0.037 and P = 0.041, respectively). One patient with the UGT1A1*28/*37 genotype presented with grade IV neutropenia and lethal septic shock. One heterozygous UGT1A1 (*1/*28) patient also carried the CYP3A4*20 allele but did not develop toxicity. We confirm that UGT1A1*37 and UGT1A1*28 are associated with severe toxicity and suggest that the CYP3A4*20 allele does not play a role in irinotecan-induced toxicity.
Filiaciones:
Riera, P:
Hosp Santa Creu i St Pau, Genet Dept, Carrer St Antoni Maria Claret 167, Barcelona 08025, Spain
UB, Fac Pharm & Food Sci, Barcelona, Spain
Salazar, J:
Hosp Santa Creu i St Pau, Genet Dept, Carrer St Antoni Maria Claret 167, Barcelona 08025, Spain
ISCIII, Ctr Biomed Res Rare Dis CIBERER, U705, Barcelona, Spain
Virgili, AC:
Hosp Santa Creu i St Pau, Med Oncol Dept, Barcelona, Spain
Tobena, M:
Hosp Santa Creu i St Pau, Med Oncol Dept, Barcelona, Spain
Sebio, A:
Hosp Santa Creu i St Pau, Med Oncol Dept, Barcelona, Spain
Gallano, P:
Hosp Santa Creu i St Pau, Genet Dept, Carrer St Antoni Maria Claret 167, Barcelona 08025, Spain
ISCIII, Ctr Biomed Res Rare Dis CIBERER, U705, Barcelona, Spain
Barnadas, A:
Hosp Santa Creu i St Pau, Med Oncol Dept, Barcelona, Spain
Paez, D:
Hosp Santa Creu i St Pau, Med Oncol Dept, Barcelona, Spain
Green Published, Bronze
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