Association of COX-2 -765G>C and -1195A>G Single Nucleotide Polymorphisms with Bladder Cancer Risk: A Case-Control Study

Year 2025, Volume: 27 Issue: 3, 326 - 332, 25.12.2025

Fatma Hande Karpuzoğlu , Murat Giriş , İlknur Bingül , Canan Küçükgergin , Mehmet Öner Şanlı , Tzevat Tefik , Selçuk Erdem , İsmet Nane , Ömer Faruk Özcan , Şule Seçkin

https://doi.org/10.18678/dtfd.1753469

Abstract

Aim: This study aimed to investigate whether functional promoter polymorphisms of the cyclooxygenase-2 (COX-2) gene, -765G>C (rs20417) and -1195A>G (rs689466), are associated with susceptibility and clinical features of bladder cancer in a Turkish population.
Material and Methods: This case-control study involved 178 patients with bladder cancer and 214 healthy controls. Genotyping was carried out using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The study statistically analyzed the associations between the polymorphisms and cancer risk, tumor grade, stage, recurrence, and smoking status.
Results: There were no significant differences between the groups in terms of age, sex, or body mass index. No statistically significant differences in genotype or allele frequencies were observed for either polymorphism between patients and controls. Furthermore, no notable association was found with tumor grade, stage, or recurrence. However, the C allele at -765G>C and the G allele at -1195A>G were slightly more common in high-grade and high-stage (T2-T4) tumors. Still, these differences did not reach statistical significance, suggesting a possible trend. Smoking was more common in patients, but showed no significant association with the polymorphisms.
Conclusion: The COX-2 -765G>C and -1195A>G polymorphisms were not associated with an increased bladder cancer risk or progression in this Turkish population. Larger, multi-ethnic studies are needed to validate these findings and explore gene-environment effects.

Keywords

Cyclooxygenase-2 , -765G>C (rs20417) , -1195A>G (rs689466) , bladder cancer , single nucleotide polymorphism

COX-2 -765G>C ve -1195A>G Tek Nükleotid Polimorfizmlerinin Mesane Kanseri Riski ile İlişkisi: Olgu-Kontrol Çalışması

Abstract

Amaç: Bu çalışmada, siklooksijenaz-2 (COX-2) geni promotör bölgesindeki -765G>C (rs20417) ve -1195A>G (rs 689466) fonksiyonel polimorfizmlerinin, Türk popülasyonunda mesane kanseri yatkınlığı ve klinik özellikleriyle ilişkili olup olmadığının araştırılması amaçlanmıştır.
Gereç ve Yöntemler: Bu olgu-kontrol çalışmasına 178 mesane kanseri hastası ve 214 sağlıklı kontrol dâhil edilmiştir. Genotipleme polimeraz zincir reaksiyonu-restriksiyon fragman uzunluk polimorfizmi (PCR-RFLP) ile gerçekleştirilmiştir. Çalışmada, polimorfizmler ile kanser riski, tümör derecesi, evresi, rekürrens ve sigara içme durumu arasındaki ilişkiler istatistiksel olarak analiz edilmiştir.
Bulgular: Gruplar arasında yaş, cinsiyet veya vücut kitle indeksi açısından anlamlı bir fark yoktu. Hastalar ve kontroller arasında her iki polimorfizm için de genotip veya alel frekansları bakımından istatistiksel olarak anlamlı bir fark gözlenmedi. Ayrıca, tümör derecesi, evresi ve rekürrens ile de belirgin bir ilişki bulunmadı. Bununla birlikte, -765G>C polimorfizmindeki C aleli ve -1195A>G polimorfizmindeki G aleli yüksek dereceli ve yüksek evreli (T2-T4) tümörlerde bir miktar daha yaygındı. Yine de, bu farklılıklar istatistiksel olarak anlamlı değildi ve bu da potansiyel bir eğilimi işaret etmektedir. Sigara kullanımı hastalar arasında anlamlı derecede daha yaygın olmakla birlikte, polimorfizmlerle anlamlı bir ilişki göstermedi.
Sonuç: COX-2 -765G>C ve -1195A>G polimorfizmleri, bu Türk popülasyonunda mesane kanseri riskinin artması veya progresyonu ile ilişkili değildir. Bu bulguların doğrulanabilmesi ve gen-çevre etkileşimlerinin araştırılabilmesi için daha geniş kapsamlı, çok etnik kökenli çalışmalara ihtiyaç vardır.

Keywords

Siklooksijenaz-2 , -765G>C (rs20417) , -1195A>G (rs689466) , mesane kanseri , tek nükleotid polimorfizmi

References

• Dyrskjøt L, Hansel DE, Efstathiou JA, Knowles MA, Galsky MD, Teoh J, et al. Bladder cancer. Nat Rev Dis Primers. 2023;9(1):58.
• Alouini S. Risk factors associated with urothelial bladder cancer. Int J Environ Res Public Health. 2024;21(7):954.
• Shala NK, Stenehjem JS, Babigumira R, Liu FC, Berge LAM, Silverman DT, et al. Exposure to benzene and other hydrocarbons and risk of bladder cancer among male offshore petroleum workers. Br J Cancer. 2023;129(5):838-51.
• van Hoogstraten LMC, Vrieling A, van der Heijden AG, Kogevinas M, Richters A, Kiemeney LA. Global trends in the epidemiology of bladder cancer: challenges for public health and clinical practice. Nat Rev Clin Oncol. 2023;20(5):287-304.
• Ulamec M, Murgić J, Novosel L, Tomić M, Terlević R, Tomašković I, et al. New insights into the diagnosis, molecular taxonomy, and treatment of bladder cancer. Acta Med Acad. 2021;50(1):143-56.
• Aghamir SMK, editor. Genetics and epigenetics of genitourinary diseases. 1st ed. Cambridge, MA, USA: Academic Press; 2024.
• Li D, Hao SH, Sun Y, Hu CM, Ma ZH, Wang ZM, et al. Functional polymorphisms in COX-2 gene are correlated with the risk of oral cancer. Biomed Res Int. 2015;2015:580652.
• Coskunpinar E, Eraltan IY, Turna A, Agachan B. Cyclooxygenase-2 gene and lung carcinoma risk. Med Oncol. 2011;28(4):1436-40.
• Mandal RK, Mittal RD. Polymorphisms in COX-2 gene influence prostate cancer susceptibility in a northern Indian cohort. Arch Med Res. 2011;42(7):620-6.
• Cossiolo DC, Costa HCM, Fernandes KBP, Laranjeira LLS, Fernandes MTP, Poli-Frederico RC. Polymorphism of the COX-2 gene and susceptibility to colon and rectal cancer. Arq Bras Cir Dig. 2017;30(2):114-7.
• Chang WS, Tsai CW, Ji HX, Wu HC, Chang YT, Lien CS, et al. Associations of cyclooxygenase-2 polymorphic genotypes with bladder cancer risk in Taiwan. Anticancer Res. 2013;33(12):5401-5.
• Agachan Cakmakoglu B, Attar R, Kahraman OT, Dalan AB, Iyibozkurt AC, Karateke A, et al. Cyclooxygenase-2 gene and epithelial ovarian carcinoma risk. Mol Biol Rep. 2011;38(5):3481-6.
• Chang WS, Liao CH, Miao CE, Wu HC, Hou LL, Hsiao CL, et al. The role of functional polymorphisms of cyclooxygenase 2 in renal cell carcinoma. Anticancer Res. 2014;34(10):5481-6.
• Siddiqi A, Saidullah B, Sultana S. Anticarcinogenic effect of hesperidin against renal cell carcinoma by targeting COX-2/PGE2 pathway in Wistar rats. Environ Toxicol. 2018;33(10):1069-77.
• Zhu W, Wei BB, Shan X, Liu P. -765G>C and 8473T>C polymorphisms of COX-2 and cancer risk: a meta-analysis based on 33 case-control studies. Mol Biol Rep. 2010;37(1):277-88.
• Gurpinar E, Grizzle WE, Piazza GA. COX-independent mechanisms of cancer chemoprevention by anti-inflammatory drugs. Front Oncol. 2013;3:181.
• Hoff JH, te Morsche RH, Roelofs HM, van der Logt EM, Nagengast FM, Peters WH. COX-2 polymorphisms -765G-->C and -1195A-->G and colorectal cancer risk. World J Gastroenterol. 2009;15(36):4561-5.
• Wang Y, Jiang H, Liu T, Tang W, Ma Z. Cyclooxygenase-2 -1195G>A (rs689466) polymorphism and cancer susceptibility: an updated meta-analysis involving 50,672 subjects. Int J Clin Exp Med. 2015;8(8):12448-62.
• Mittal M, Kapoor V, Mohanti BK, Das SN. Functional variants of COX-2 and risk of tobacco-related oral squamous cell carcinoma in high-risk Asian Indians. Oral Oncol. 2010;46(8):622-6.
• Gharib AF, Karam RA, Abd El Rahman TM, Elsawy WH. COX-2 polymorphisms -765G→C and -1195A→G and hepatocellular carcinoma risk. Gene. 2014;543(2):234-6.
• Hou L, Grillo P, Zhu ZZ, Lissowska J, Yeager M, Zatonski W, et al. COX1 and COX2 polymorphisms and gastric cancer risk in a Polish population. Anticancer Res. 2007;27(6C):4243-7.
• van Nes JG, de Kruijf EM, Faratian D, van de Velde CJ, Putter H, Falconer C, et al. COX2 expression in prognosis and in prediction to endocrine therapy in early breast cancer patients. Breast Cancer Res Treat. 2011;125(3):671-85.
• Vogel U, Christensen J, Wallin H, Friis S, Nexø BA, Tjønneland A. Polymorphisms in COX-2, NSAID use and risk of basal cell carcinoma in a prospective study of Danes. Mutat Res. 2007;617(1-2):138-46.
• Souza RF, Shewmake K, Beer DG, Cryer B, Spechler SJ. Selective inhibition of cyclooxygenase-2 suppresses growth and induces apoptosis in human esophageal adenocarcinoma cells. Cancer Res. 2000;60(20):5767-72.
• Kujubu DA, Reddy ST, Fletcher BS, Herschman HR. Expression of the protein product of the prostaglandin synthase-2/TIS10 gene in mitogen-stimulated Swiss 3T3 cells. J Biol Chem. 1993;268(8):5425-30.
• Zhou F, Gao G, Ren S, Li X, He Y, Zhou C. The association between COX-2 polymorphisms and hematologic toxicity in patients with advanced non-small-cell lung cancer treated with platinum-based chemotherapy. PLoS One. 2013;8(4):e61585.
• Gong J, Bostick RM, Xie D, Hurley TG, Deng Z, Dixon DA, et al. Genetic polymorphisms in the cyclooxygenase-1 and cyclooxygenase-2 genes and risk of colorectal adenoma. Int J Colorectal Dis. 2009;24(6):647-54.
• Chang WS, Yang MD, Tsai CW, Cheng LH, Jeng LB, Lo WC, et al. Association of cyclooxygenase 2 single-nucleotide polymorphisms and hepatocellular carcinoma in Taiwan. Chin J Physiol. 2012;55(1):1-7.
• Wan GX, Chen P, Yu XJ, Di QS, Yu YD, Lei JH, et al. Cyclooxygenase-2 polymorphisms and bladder cancer risk: a meta-analysis based on case-control studies. Int J Clin Exp Med. 2015;8(3):3935-45.