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

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.

chemotherapy,fluoropyrimidines, 5-fluorouracil,colorectal cancer, gastric cancer , dihydropyrimidine ehydrogenase, pharmacogenetics