MTHFR and VDR Polymorphisms Improve the Prognostic Value of MYCN Status on Overall Survival in Neuroblastoma Patients

被引:8
|
作者
Olivera, Gladys G. [1 ,2 ]
Yanez, Yania [3 ]
Gargallo, Pablo [4 ]
Sendra, Luis [1 ,2 ]
Alino, Salvador F. [1 ,2 ,5 ]
Segura, Vanessa [4 ]
Angel Sanz, Miguel [6 ]
Canete, Adela [4 ]
Castel, Victoria [4 ]
Font De Mora, Jaime [3 ]
Hervas, David [7 ]
Berlanga, Pablo [8 ]
Jose Herrero, Maria [1 ,2 ]
机构
[1] Inst Invest Sanitaria La Fe, Pharmacogenet Platform, Valencia 46026, Spain
[2] Univ Valencia, Dept Pharmacol, Valencia 46010, Spain
[3] Inst Invest Sanitaria La Fe, Clin & Translat Res Canc, Valencia 46026, Spain
[4] Hosp Univ & Politecn La Fe, Pediat Oncol Unit, Valencia 46026, Spain
[5] Hosp Univ & Politecn La Fe, Clin Pharmacol Unit, Valencia 46026, Spain
[6] Hosp Univ & Politecn La Fe, Hematol & Hemotherapy Serv, Valencia 46026, Spain
[7] Inst Invest Sanitaria La Fe, Data Sci Biostat & Bioinformat Platform, Valencia 46026, Spain
[8] Inst Gustave Roussy Ctr, Dept Pediat & Adolescent Oncol, F-94800 Villejuif, France
关键词
pharmacogenetics; neuroblastoma; survival; toxicity; SNP; HIGH-RISK NEUROBLASTOMA; BREAST-CANCER PATIENTS; RAPID COJEC INDUCTION; REDUCTASE; THERAPY; PHARMACOGENOMICS; REGULARIZATION; DOXORUBICIN; EXPRESSION;
D O I
10.3390/ijms21082714
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Single nucleotide polymorphisms (SNPs) in Pharmacogenetics can play an important role in the outcomes of the chemotherapy treatment in Neuroblastoma, helping doctors maximize efficacy and minimize toxicity. Employing AgenaBioscience MassArray, 96 SNPs were genotyped in 95 patients looking for associations of SNP with response to induction therapy (RIT) and grade 3-4 toxicities, in High Risk patients. Associations of SNPs with overall (OS) and event-free (EFS) survival in the whole cohort were also explored. Cox and logistic regression models with Elastic net penalty were employed. Association with grade 3-4 gastrointestinal and infectious toxicities was found for 8 different SNPs. Better RIT was correlated with rs726501 AG, rs3740066 GG, rs2010963 GG and rs1143684 TT (OR = 2.87, 1.79, 1.23, 1.14, respectively). EFS was affected by rs2032582, rs4880, rs3814058, rs45511401, rs1544410 and rs6539870. OS was influenced by rs 1801133, rs7186128 and rs1544410. Remarkably, rs1801133 in MTHFR (p = 0.02) and rs1544410 in VDR (p = 0.006) also added an important predictive value for OS to the MYCN status, with a more accurate substratification of the patients. Although validation studies in independent cohorts will be required, the data obtained supports the utility of Pharmacogenetics for predicting Neuroblastoma treatment outcomes.
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页数:18
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