Baş boyun kanserli hastalarda tek gen polimorfizmi ile sisplatin ve 5-FU tedavisine yanıt arasındaki ilişki

Yıl 2023, , 414 - 419, 30.09.2023

Aydın Demiray , Ege Rıza Karagür , Hakan Akça , Onur Tokgün , Atike Gökçen Demiray , Ferda Bir

https://doi.org/10.18663/tjcl.1349948

Öz

Amaç: Baş ve boyun kanserleri dünya çapında en sık görülen altıncı kanser türüdür. Baş ve boyun kanserlerinin tedavi süreci kemoterapi veya kemoradyoterapi olarak sınıflandırılır. Bu çalışmada ERCC1, XRCC1 ve MTHFR genlerinin tedavi ile yanıt ilişkisi araştırıldı.
Gereç ve Yöntemler: Çalışmada tek nükleotid polimorfizmini araştırmak amacıyla hastalardan 5 ml kan alınarak DNA izole edildi ve pirosequencing yöntemiyle araştırıldı.
Bulgular: Hastalar RECIST kriterlerine göre değerlendirildi; tedaviden önce (4 hafta) ve her üç siklustan sonra baş ve boyun bilgisayarlı tomografi taramaları yapıldı. Genel yanıt oranı (RR) 10 (%25) PD, 7 (%17,5) SD, 9 (%22,5) PR ve 14 (%35) CR idi. En az bir polimorfik varyantı olan hastaların dördünde PD, 3'ünde SD, 3'ünde PR ve 1'inde CR vardı.
Sonuçlar: Bu çalışmada bir grup baş boyun karsinomu hastasının klinik davranışı, üç tek nükleotid polimorfizmi ile ilişki açısından retrospektif olarak değerlendirildi. Bunlar arasında ERCC1 geninde C8092A, XRCC1 geninde G28152A ve MTHFR geninde C677T ve A1298C yer alıyordu.

Anahtar Kelimeler

Baş ve boyun kanseri, SNP, cisplatin, 5-FU

The relationship between single gene polymorphism and response to cisplatin and 5-FU treatment in patients with head and neck cancer

Öz

Aim: Head and neck cancers are the sixth most common type of cancer worldwide. The treatment process of head and neck cancers is classified as chemotherapy or chemoradiotherapy. In this study, the relationship of ERCC1, XRCC1 and MTHFR genes with treatment response was investigated.
Material and Methods: In the study, 5 ml of blood was collected from the patients to investigate single nucleotide polymorphism, DNA was isolated and investigated by pyrosequencing method.
Results: Patients were evaluated according to RECIST criteria; head and neck computed tomography scans were performed before treatment (4 weeks) and after every three cycles. The overall response rate (RR) was 10 (25%) PD, 7 (17.5%) SD, 9 (22.5%) PR, and 14 (35%) CR. Of the patients who presented with at least one polymorphic variant, four had PD, 3 had SD, 3 had PR and 1 had CR.
Conclusion: In this study, the clinical behaviour of a group of head and neck carcinoma patients was retrospectively evaluated for association with three single nucleotide polymorphisms. These included C8092A in the ERCC1 gene, G28152A in the XRCC1 gene, and C677T and A1298C in the MTHFR gene.

Anahtar Kelimeler

Head and neck cancer, SNP, cisplatine, 5-FU

Kaynakça

• Atashi F, Vahed N, Emamverdizadeh P, Fattahi S, Paya L. Drug resistance against 5-fluorouracil and cisplatin in the treatment of head and neck squamous cell carcinoma: A systematic review. J Dent Res Dent Clin Dent Prospects. 2021;15(3):219-225
• Chi AC, Day TA, Neville BW. Oral cavity and oropharyngeal squamous cell carcinoma--an update. CA Cancer J Clin. 2015;65(5):401-21
• Watts TL, Cui R, Szaniszlo P, Resto VA, Powell DW, Pinchuk IV. PDGF- AA mediates mesenchymal stromal cell chemotaxis to the head and neck squamous cell carcinoma tumor microenvironment. J Transl Med. 2016;14(1):337
• Kumar S, Kumar A, Shah PP, Rai SN, Panguluri SK, Kakar SS. MicroRNA signature of cis-platin resistant vs. cis-platin sensitive ovarian cancer cell lines. J Ovarian Res. 2011;4(1):17.
• Qiao LL, Yao WJ, Zhang ZQ, Yang X, Zhao MX. The biological activity research of the nano-drugs based on 5-fluorouracil- modified quantum dots. Int J Nanomedicine. 2020;15:2765-76.
• Zhou F, Yu Z, Jiang T, Lv H, Yao R, Liang J. Genetic polymorphisms of GSTP1 and XRCC1: prediction of clinical outcome of platinum- based chemotherapy in advanced non-small cell lung cancer (NSCLC) patients. Swiss Med Wkly. 2011;19:141-152
• Benzeid R, Gihbid A, Tawfiq N, et al., Chaoui I, Khyatti M, El Mzibri M. Genetic Polymorphisms in ERCC1 Gene and Their Association with Response to Radiotherapy in Moroccan Patients with Nasopharyngeal Carcinoma. Asian Pac J Cancer Prev. 2023;24(1):93-99.
• Palomba G, Atzori F, Budroni et al. ERCC1 polymorphisms as prognostic markers in T4 breast cancer patients treated with platinum-based chemotherapy. J Transl Med. 2014;12:272
• De Castro G Jr, Pasini FS, Siqueira SA, Ferraz AR, Villar RC, Snitcovsky IM, Federico MH. ERCC1 protein, mRNA expression and T19007C polymorphism as prognostic markers in head and neck squamous cell carcinoma patients treated with surgery and adjuvant cisplatin-based chemoradiation. Oncol Rep. 2011 Mar;25(3):693-9.
• Yeh CC, Lai CY, Chang SN, Hsieh LL, Tang R, Sung FC, Lin YK. Polymorphisms of MTHFR C677T and A1298C associated with survival in patients with colorectal cancer treated with 5-fluorouracil-based chemotherapy. Int J Clin Oncol. 2017;22(3):484-493.
• Niu YM, Deng MH, Chen W, Zeng XT, Luo J. MTHFR C677T gene polymorphism and head and neck cancer risk: a meta-analysis based on 23 publications. Dis Markers. 2015;2015:681313.
• Quintela-Fandino M, Hitt R, Medina PP, Gamarra S, Manso L, Cortes-Funes H, Sanchez-Cespedes M. DNA-repair gene polymorphisms predict favorable clinical outcome among patients with advanced squamous cell carcinoma of the head and neck treated with cisplatin-based induction chemotherapy. J Clin Oncol. 2006;24(26):4333-9
• Vaezi A, Feldman CH, Niedernhofer LJ. ERCC1 and XRCC1 as biomarkers for lung and head and neck cancer. Pharmgenomics Pers Med. 2011;4:47-63
• Li DJ, Xiao D. Association between the XRCC1 polymorphisms and clinical outcomes of advanced NSCLC treated with platinum-based chemotherapy: a meta-analysis based on the PRISMA statement. BMC Cancer. 2017 Jul 25;17(1):501.
• Yong-lian Zhang, Xiong-wei Xie Methylenetetrahydrofolate reductase C677T polymorphism and toxicity to 5-FU-based chemotherapy in colorectal Cancer Tropical Journal of Pharmaceutical Research January 2020; 19 (1): 209-213