The role of personalized medicine in fluoropyrimidine-based chemotherapy: Identification of predictive markers in chemotherapy treatment

سال انتشار: 1395
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 438

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شناسه ملی سند علمی:

IPMCMED01_175

تاریخ نمایه سازی: 23 آذر 1397

چکیده مقاله:

Introduction & Aim: The fluoropyrimidine drug 5-fluorouracil (5-FU) and the prodrug capecitabine, have been extensively used for treatment of many types of cancer including colorectal, gastric and head and neck. Approximately 10% of the patients suffer from severe fluoropyrimidine-induced toxicity, like diarrhea, mucositis, myelosuppression and hand-foot syndrome. This may lead to dose reduction and treatment discontinuation. Pharmacogenetics research could be useful for identification of predictive markers in chemotherapy treatment. Methods: Germline DNA was extracted from 83 cancer patients treated with fluoropyrimidine-based chemotherapy in Hazrat Rasool-e Akram Hospital . In this study, we genotyped three polymorphisms in dihyropyrimidine dehydrogenase gene (rs3918290),(rs67376798),(rs55886062) and two polymorphisms, The variable number of tandem repeat (VNTR) polymorphism (rs45445694) and 6-bp insertion/deletion polymorphism(rs151264360) in thymidylate synthase gene. These genetic markers were correlated with toxicity to treatment. 5-FU-related toxicities such as Anemia, febrile neutropenia, neurotoxicity, vomiting, nausea and mucositis were evaluated according to NCI-CTC criteria version 4.0 . Results: DPYD gene polymorphisms was not observed in this study. The frequency of the TYMS +6 bp allele was 40.35% and the -6 bp allele was 59.65% in this study. And frequency of VNTR 2R allele was 48.75% and 3R allele was 51.15% .Toxicity grade two diarrhea,mucositis,nausea,vomiting and neurotoxicity are 2.2%,24.1%,15.7%,6% and 51.8%, respectively . Thymidylate synthase ins/del polymorphisms was significantly associated with increased grade three Neurotoxicity (p=0.02) . Conclusion: A pharmacogenetic approach could be a useful strategy for personalizing chemotherapy in cancer patients. Although rare DPYD polymorphisms was not observed in our study, according to large population studies, DPYD gene polymorphisms could be used as a predictive biomarker for efficacy of fluoropyrimidene-based chemotherapy . This study is currently underway to evaluate the role of thymidylate synthase polymorphisms in Progression-Free Survival, and Overall Survival in cancer patients.

نویسندگان

Mohamad Hadi Abasian

National institute of genetic engineering and biotechnology (nigeb)

Bahareh Abbasi

Department of Medical Genetic, Medical Biotechnology Ins., National Institute of Genetic Engineering and iotechnology (NIGEB), Tehran, IR Iran

Nafiseh Ansarinejad

Department of Hematology and Oncology, Hazrat Rasool-e Akram Hospital, Iran University of Medical Sciences, Tehran, IR Iran

Farshid Fardad

Department of Hematology and Oncology, Hazrat Rasool-e Akram Hospital, Iran University of Medical Sciences, Tehran, IR Iran