Identification of polymorphic variants correlated to taxanes neurotoxicity in breast cancer patients by Dmet microarray platform. (Abstract/Poster in atti di convegno)

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  • Identification of polymorphic variants correlated to taxanes neurotoxicity in breast cancer patients by Dmet microarray platform. (Abstract/Poster in atti di convegno) (literal)
Anno
  • 2013-01-01T00:00:00+01:00 (literal)
Alternative label
  • Arbitrio M.(1), Viscomi C. (2), Di Martino M. T. (3), Botta C. (5), Costantino A. (2), Altomare E. (5), Fabiani F. (6), Guzzi P. H. (4), Cannataro M. (4), Tassone P. (3), Tagliaferri P (3). (2013)
    Identification of polymorphic variants correlated to taxanes neurotoxicity in breast cancer patients by Dmet microarray platform.
    in XV National Congress of Medical Oncology, Milano, 11-13 Ottobre
    (literal)
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  • Arbitrio M.(1), Viscomi C. (2), Di Martino M. T. (3), Botta C. (5), Costantino A. (2), Altomare E. (5), Fabiani F. (6), Guzzi P. H. (4), Cannataro M. (4), Tassone P. (3), Tagliaferri P (3). (literal)
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  • XV Congresso Nazionale AIOM 2013 (literal)
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  • 1/L21 (literal)
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  • 14 (literal)
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  • Poster (literal)
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  • 1 CNR-Institute of Neurological Sciences-UOS of Pharmacology-Catanzaro- 2 Medical Oncology Unit, T. Campanella Cancer Center, Catanzaro- 3 Department of Experimental and Clinical Medicine, Magna Graecia University and Medical Oncology Unit, T. Campanella Cancer Center, Catanzaro- 4 Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro - 5 Department of Experimental and Clinical Medicine, Magna Graecia University and Medical Oncology Unit, Catanzaro - 6 Medical Genetic Unit, Magna Graecia University, Catanzaro (literal)
Titolo
  • Identification of polymorphic variants correlated to taxanes neurotoxicity in breast cancer patients by Dmet microarray platform. (literal)
Abstract
  • Background: Peripheral neuropathy is a disabling taxane-related adverse event. Genetic polymorphisms (GP) in drug transporters and drug-metabolizing enzymes (ADME) could be involved in taxane-associated neuropathy (TAN). We investigated the correlation between single nucleotide polymorphisms (SNPs) linked to ADME gene variants and >= grade 3 (G3) TAN by the drug-metabolizing enzyme and transporter (DMET) microarray Affymetrix platform. Patients and methods: Seventy-nine taxane-treated breast cancer patients, were enrolled in a case-control study: 27 experienced TAN (>= G3) while 52 were no-TAN matched controls. Peripheral blood cells DNA was genotyped by DMET Plus chip. The study primary end-point was association between ADME-related SNPs and TAN; secondary endpoints were the association between TAN-related SNPs and treatment response or Progression Free Survival (PFS). Genotype association was analyzed by Fisher exact test and relevant SNPs were analyzed through Log-Rank test and Cox proportional hazards model. Results: Nine SNPs significantly associated with TAN. After Bonferroni's correction only a SNP on NAT2 gene (rs1041983), remained significantly associated to TAN (<= 0.003): the T/T genotype of the rs1041983 SNP showed the strongest association with >=G3 neurotoxicity, being genotyped in 10/27 cases vs. 4/51 control patients (p=0.003, OR=6.911, 95% CI=1.9114 to 24.9939). Polymorphic variants in rs3808607 (CYP7A1) and in rs2292954 (SPG7) SNPs were associated to treatment response. The genotype A/C of the rs3808607 SNP, was found in 5/17 patients with Partial Response (PR), in 5/5 patients with Complete Response(CR) and 0/13 patients with Stable Disease (SD)/Progressive Disease (PD) (p=0.003) while the genotype A/G of rs2292954 SNP was found in 8/18 patients with PR, 4/5 with CR and 2/12 SD/PD (p=0.001). TAN did not correlate with clinical outcome. The rs562 polymorphism (genotype C/C) mapping in the ABCC5 gene was correlated to prolonged PFS (median not reached). The G/G genotype only slightly correlated with TAN, wasn't associated to response and showed an intermediate PFS (median 13.8 months). The C/G genotype was associated with a worse PFS (median 12.07 months). Conclusions: A polymorphic variant of NAT2 gene was correlated to TAN, while polymorphic variant of CYP7A1, SPG7 and ABCC5 genes were correlated to treatment response and PFS. DMET can identify GP for personalized therapeutic strategies. (literal)
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