| Autor: |
Emelyanova M; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia., Pokataev I; Department of Oncology, Moscow Clinical Oncology Hospital No.1, Moscow City Health Department, 105005 Moscow, Russia., Shashkov I; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia.; Federal Research Centre 'Fundamentals of Biotechnology', Russian Academy of Sciences, 119071 Moscow, Russia., Kopantseva E; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia., Lyadov V; Department of Oncology, Moscow Clinical Oncology Hospital No.1, Moscow City Health Department, 105005 Moscow, Russia.; Department of Oncology and Palliative Medicine, Russian Medical Academy of Continuous Professional Education, 123242 Moscow, Russia.; Department of Oncology, Novokuznetsk State Institute for Continuous Medical Education, 654005 Novokuznetsk, Russia., Heydarov R; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia., Mikhailovich V; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia. |
| Abstrakt: |
Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal malignancy that has the worst 5-year survival rate of all of the common malignant tumors. Surgery, chemotherapy, and/or chemoradiation remain the main tactics for PDAC treatment. The efficacy of chemotherapy is often compromised because of the substantial risk of severe toxicities. In our study, we focused on identification of polymorphisms in the genes involved in drug metabolism, DNA repair and replication that are associated with inter-individual differences in drug-induced toxicities. Using the microarray, we genotyped 12 polymorphisms in the DPYD , XPC , GSTP1 , MTHFR , ERCC1 , UGT1A1 , and TYMS genes in 78 PDAC patients treated with FOLFIRINOX. It was found that the TYMS rs11280056 polymorphism (6 bp-deletion in TYMS 3'-UTR) predicted grade 1-2 neurotoxicity ( p = 0.0072 and p = 0.0019, according to co-dominant (CDM) and recessive model (RM), respectively). It is the first report on the association between TYMS rs11280056 and peripheral neuropathy. We also found that PDAC patients carrying the GSTP1 rs1695 GG genotype had a decreased risk for grade 3-4 hematological toxicity as compared to those with the AA or AG genotypes ( p = 0.032 and p = 0.014, CDM and RM, respectively). Due to relatively high p -values, we consider that the impact of GSTP1 rs1695 requires further investigation in a larger sample size. |
