Over kanserli hastalardaki ERCC1 ve ABCB1 gen polimorfizminin platin ve taksan tedavisine yanıt ile ilişkisi

Year 2020, Volume: 13 Issue: 2, 363 - 367, 14.05.2020

Atike Gökçen Demiray , Arzu Yaren Aydın Demiray , Burcu Yapar , Serkan Değirmencioğlu , Gamze Gököz-doğu , Hakan Akça

https://doi.org/10.31362/patd.696862

Abstract

Özet
Amaç: Kanser kemoterapisine yanıtta bireysel farklılıkların oluşmasında genetik polimorfizmlerin rolü büyüktür. Gen polimorfizmleri ve mutasyonlar, kombinasyon kemoterapi tedavilerinde, yaygın olarak kullanılan ilaçların metabolizmalarını etkileyebilmektedirler.Bu sebeple, bu polimorfizmlerin belirlenmesinin, birçok kanser türünde, kemoterapiye klinik yanıt ya da kemoterapi ilişkili toksisiteyi öngörmede etkili olabilecekleri düşünülmektedir. Bizde çalışmamızda bu amaçla over kanseri hastalarında ERCC1 geni C8092A ve T19007C ile ABCB1 (MDR1) geni C3435T tek nükleotit değişiminin platin ve taksan tedavisine yanıtta bir etkisinin olup olmadığını araştırmayı planladık
Gereç ve Yöntem: Çalışmamıza Pamukkale Üniversitesi Tıp Fakültesi Tıbbi Onkoloji Polikliniğinde takipli 20 over kanser tanılı hasta dahil edildi. Hastalardan 5ml tam kan alındı. Toplanan tam kanlardan DNA izolasyonu qiagen miniBlood kit kullanılarak elde edildi. Elde edilen DNA’lardan pyrosequencing sistem kullanılarak tek gen değişimi analiz edildi. İstatistik, Statistical Package for Social Sciences version17 ile hesaplandı. Sonuçlar %95 güven aralığında değerlendirildi. p<0,05 olması istatistiksel olarak anlamlı kabul edildi.
Bulgular: Hastalarımızın ortanca yaş değeri 61 yıl idi. (sınırlar: 46-73 yıl). Hastalardan 8 i evre 3c ve 12’si evre 4’tü. Histopatolojik olarak, 18 i seröz papiller, 2’si berrak hücreli olarak tanımlanmıştı. ERCC1 geni C8092A değişimi; 14 hastada wild tip iken 6 hastada heterozigot veya mutant, ERCC1 geni T19007C değişimi; 5 hastada wild (yaban tip) iken 15 hastada heterozigot veya mutant olarak saptanmıştır. ABCB1 (MDR1) geni C3435T değişimi; 11 hastada wild iken 9 hastada heterozigot veya mutant olarak analiz edilmiştir. ERCC1 ve ABCB1 geni tek nükleotit değişimi araştırılan 20 hastanın progrese olma süreleri arasında istatistiksel olarak anlamlı bir fark bulunamamıştır. Ancak ERCC1 geni C8092A wild tip olan hastaların ortalama sağkalım süresi anlamlı olarak daha fazladır
Sonuç: Gen polimorfizmleri tedaviye yanıtı ön görmede yol gösterici bir belirteç olarak kullanılabilir. Polimorfizmi taşıyan hastaların belirlenmesi klinisyenlerin kemoterapi tedavilerini bireyselleştirmelerine yardımcı olacaktır. Farmakogenetik yaklaşımlı daha fazla hastanın dahil edildiği geniş çaplı çalışmalara ihtiyaç vardır.

Anahtar Kelimeler: Over kanseri,ERCC1,ABCB1,platin,taksan

Abstract
Purpose: Genetic polymorphisms play a major role in the individual differences in response to cancer chemotherapy. Gene polymorphisms and mutations can affect the metabolism of commonly used drugs in combination chemotherapy treatments. Therefore, it is thought that the detection of these polymorphisms may be effective in predicting clinical response to chemotherapy or chemotherapy-related toxicity in many types of cancer. In this study, we planned to investigate whether ERCC1 gene C8092A and T19007C and ABCB1 (MDR1) gene C3435T single nucleotide change have an effect on platinum and taxane treatment in ovarian cancer patients.
Materials and Methods: Twenty patients diagnosed with ovarian cancer were included in our study at Pamukkale University Medical Faculty Medical Oncology Outpatient Clinic . Five ml serum blood was taken from the patients. DNA isolation from collected serum blood was obtained using the qiagen miniBlood kit.Single gene exchange was analyzed using the pyrosequencing system from the DNA obtained.The analyses were carried out using SPSS v17. The results were evaluated within the 95% confidence interval. p <0.05 was considered statistically significant.
Results: The median age of our patients was 61 years. (limits: 46-73 years). Eight of the patients were stage 3c and 12 were stage 4. Histopathologically, 18 were defined as serous papillary and 2 were clear cell. ERCC1 gene C8092A replacement; While 14 patients were wild type, 6 patients had heterozygous or mutant, ERCC1 gene T19007C change; It was wild in 5 patients, and heterozygous or mutant in 15 patients. ABCB1 (MDR1) gene C3435T replacement; It was analyzed as heterozygous or mutant in 9 patients while wild in 11 patients. No statistically significant difference was found between the progression time of 20 patients whose ERCC1 and ABCB1 gene single nucleotide changes were investigated.
However, the median survival time of patients with ERCC1 gene C8092A wild type is significantly higher.
Conclusion: Gene polymorphisms can be a biomarker in predicting treatment response. Identifying patients with polymorphism will help clinicians individualize chemotherapy treatments.
Large studies are needed, involving more patients with a pharmacogenetic approach

Key Words: Ovarian cancer, ERCC1,ABCB1,platın,taxane

Keywords

over kanseri, ERCC1, ABCB1, platin, taksan

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