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Pharmacogenomics. 2018 Jan;19(2):105-112. doi: 10.2217/pgs-2017-0153. Epub 2017 Dec 6.

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

Author information

1
Pediatric Hematology-Oncology Unit & Pediatric Hematology-Oncology Research Laboratory, Division of Pediatrics, Department of Woman-Mother-Child, University Hospital of Lausanne, 1004 Lausanne, Switzerland.
2
Charles-Bruneau Cancer Center, CHU Sainte-Justine Research Center, Montreal, QC, H3T1C5, Canada.
3
Department of Pediatrics, University of Milano-Bicocca, Ospedale S Gerardo, 20835 Monza, Italy.
4
Department of Pediatric Hemato-Oncology, Santobono-Pausilipon Hospital, 80129 Naples, Italy.
5
Department of Woman & Child Health, Laboratory of Haematology-Oncology, University of Padova, 35128 Padova, Italy.
6
Centro Ricerca Tettamanti, Department of Pediatrics, University Milano Bicocca, 20835 Monza, Italy.
7
Department of Pediatrics, Faculty of Medicine, University of Montreal, Montreal, QC, H4A 3J1, Canada.
8
Department of Pharmacology & Physiology, Faculty of Medicine, University of Montreal, Montreal, QC, H3C 3J7, Canada.

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.

KEYWORDS:

childhood ALL; dihydrofolate reductase polymorphisms; treatment outcome

PMID:
29210328
DOI:
10.2217/pgs-2017-0153
[Indexed for MEDLINE]

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