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2 results on '"dihydrofolate reductase polymorphism"'

1. DNA variants in DHFR gene and response to treatment in children with childhood B ALL: Revisited in AIEOP-BFM protocol

Author

Ceppi, F, Gagné, V, Douyon, L, Quintin, C, Colombini, A, Parasole, R, Buldini, B, Basso, G, Conter, V, Cazzaniga, G, Krajinovic, M, Ceppi, Francesco, Gagné, Vincent, Douyon, Laurance, Quintin, Camille J., Colombini, Antonella, Parasole, Rosanna, Buldini, Barbara, Basso, Giuseppe, Conter, Valentino, Cazzaniga, Giovanni, Krajinovic, Maja, Ceppi, F, Gagné, V, Douyon, L, Quintin, C, Colombini, A, Parasole, R, Buldini, B, Basso, G, Conter, V, Cazzaniga, G, Krajinovic, M, Ceppi, Francesco, Gagné, Vincent, Douyon, Laurance, Quintin, Camille J., Colombini, Antonella, Parasole, Rosanna, Buldini, Barbara, Basso, Giuseppe, Conter, Valentino, Cazzaniga, Giovanni, and Krajinovic, Maja

Abstract

Aim: We have previously reported an association of dihydrofolate reductase promoter polymorphisms with reduced event-free survival in childhood acute lymphoblastic leukemia (ALL) patients treated with Dana Farber Cancer Institute protocol. Here, we assessed whether these associations are applicable to other protocol, based on different methotrexate doses. Methods: Genotypes for six tag polymorphisms and resulting haplotypes were analyzed for an association with ALL outcome. Results: The association was found with the polymorphisms A-680C, A-317G and C-35T in high-risk group patients. Carriers of haplotype ∗1 had a remarkably higher risk of events compared with noncarriers and a lower probability of event-free survival (21.4 vs 81.3%). Conclusion: The role of DHFR variants in predicting the outcome of childhood ALL extends beyond single-treatment protocol and can be useful biomarker in personalizing treatment.

Published
2018

2. DNA variants in DHFR gene and response to treatment in children with childhood B ALL: Revisited in AIEOP-BFM protocol

Author

Maja Krajinovic, Laurance Douyon, Vincent Gagné, Barbara Buldini, Camille J Quintin, Giovanni Cazzaniga, Giuseppe Basso, Francesco Ceppi, Rosanna Parasole, Antonella Colombini, Valentino Conter, Ceppi, F, Gagné, V, Douyon, L, Quintin, C, Colombini, A, Parasole, R, Buldini, B, Basso, G, Conter, V, Cazzaniga, G, and Krajinovic, M

Subjects
0301 basic medicine, Oncology, Male, MED/03 - GENETICA MEDICA, chemistry.chemical_compound, 0302 clinical medicine, Dihydrofolate reductase, Genotype, Antineoplastic Combined Chemotherapy Protocols, Child, Promoter Regions, Genetic, dihydrofolate reductase polymorphisms, Tumor, biology, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Vincristine, 030220 oncology & carcinogenesis, Molecular Medicine, Biomarker (medicine), Female, medicine.drug, medicine.medical_specialty, Asparaginase, dihydrofolate reductase polymorphism, childhood ALL, treatment outcome, Biomarkers, Tumor, DNA, Daunorubicin, Disease-Free Survival, Haplotypes, Humans, Methotrexate, Polymorphism, Genetic, Prednisone, Tetrahydrofolate Dehydrogenase, Treatment Outcome, Genetics, Pharmacology, Promoter Regions, 03 medical and health sciences, Genetic, Internal medicine, medicine, Polymorphism, Childhood Acute Lymphoblastic Leukemia, business.industry, Haplotype, 030104 developmental biology, chemistry, biology.protein, business, Biomarkers
Abstract

Aim: We have previously reported an association of dihydrofolate reductase promoter polymorphisms with reduced event-free survival in childhood acute lymphoblastic leukemia (ALL) patients treated with Dana Farber Cancer Institute protocol. Here, we assessed whether these associations are applicable to other protocol, based on different methotrexate doses. Methods: Genotypes for six tag polymorphisms and resulting haplotypes were analyzed for an association with ALL outcome. Results: The association was found with the polymorphisms A-680C, A-317G and C-35T in high-risk group patients. Carriers of haplotype *1 had a remarkably higher risk of events compared with noncarriers and a lower probability of event-free survival (21.4 vs 81.3%). Conclusion: The role of DHFR variants in predicting the outcome of childhood ALL extends beyond single-treatment protocol and can be useful biomarker in personalizing treatment.

Published
2018

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