Meme Kanseri Riskinde ARTN ve PSPN Gen Polimorfizmlerinin Değerlendirilmesi: Türk Popülasyonunda Bir Vaka-Kontrol Çalışması

Yıl 2026, Cilt: 48 Sayı: 1, 1 - 6, 15.12.2025

Tuba Taşkan Susam , Osman Kurukahvecioğlu , Niyazi Karaman , Aymelek Gönenç

https://doi.org/10.20515/otd.1684002

Öz

RET, çeşitli dokuların normal gelişimi ve olgunlaşması için gerekli olan reseptör tirozin kinaz ailesinin bir üyesidir. RET sinyalizasyonu, çevredeki stromayı ve hücre kompozisyonunu değiştiren tümör mikroçevresindeki değişiklikleri teşvik eder. RET ve ligandları artemin (ARTN) ve persefin (PSPN) gen polimorfizmleri, kanser patogenezi, riski, invazyonu ve metastazında bir araştırma odağıdır. RET polimorfizmleri birçok etnik köken ve popülasyonda çeşitli kanserlerde araştırılmış olsa da, literatürde ARTN ve PSPN polimorfizmlerinin meme kanseri riski üzerindeki etkisine ilişkin sınırlı sayıda çalışma bulunmaktadır. Çalışmaya 102 meme kanseri hastası ve 102 sağlıklı kontrol dahil edildi. rs3762422 ve rs2304198 polimorfizmleri polimeraz zincir reaksiyonu ve dizileme yöntemleri ile tespit edildi ve genotip dağılımları belirlendi. Çalışma grupları her iki varyantta da genotip dağılımları açısından benzer bir profil gösterdi ve istatistiksel olarak anlamlı bir fark bulunmadı (sırasıyla p>0,05, p>0,05). Bulgularımız, ARTN rs3762422 ve PSPN rs2304198 polimorfizmlerinin kohortumuzda meme kanseri riskiyle ilişkili olmadığını göstermektedir. Bu çalışmada ARTN geni rs3762422 ve PSPN geni rs2304198 varyantları ile meme kanseri arasındaki olası riski araştırmayı ve değerlendirmeyi amaçladık. Bilgilerimize göre bu çalışma meme kanserindeki bu varyantları araştıran ilk çalışmadır ve gelecekteki araştırmalara katkıda bulunabilir.

Anahtar Kelimeler

Meme Kanseri , RET , Artemin , Persephin , Polimorfizm

Proje Numarası

22.GENEL.023

Evaluation of ARTN and PSPN Gene Polymorphisms in Breast Cancer Risk: Insights from a Case-Control Study in Turkish Population

Öz

RET is a member of the receptor tyrosine kinase family, which is essential for the normal development and maturation of various tissues. RET signaling promotes changes in the tumor microenvironment that alter the surrounding stroma and cellular composition. Gene polymorphisms of RET and its ligands artemin (ARTN) and persephin (PSPN) are a research focus in cancer pathogenesis, risk, invasion, and metastasis. Although RET polymorphisms have been investigated in various cancers in many ethnicities and populations, there are limited studies in the literature on the effect of ARTN and PSPN polymorphisms on breast cancer risk. The study included 102 breast cancer patients and 102 healthy controls. rs3762422 and rs2304198 polymorphisms were detected by polymerase chain reaction and sequencing methods and genotype distributions were determined. The study groups showed a similar profile in terms of genotype distributions in both variants and no statistically significant difference was found (p>0.05, p>0.05, respectively). Our findings suggest that ARTN rs3762422 and PSPN rs2304198 polymorphisms are not associated with breast cancer risk in our cohort. In this study, we aimed to investigate and evaluate the possible risk between ARTN gene rs3762422 and PSPN gene rs2304198 variants and breast cancer. To our knowledge, this is the first study investigating these variants in breast cancer, and it may contribute to future research.

Anahtar Kelimeler

Breast Cancer , RET , Artemin , Persephin , Polymorphism

Etik Beyan

In accordance with the Helsinki declaration, Afyonkarahisar Health Sciences University Clinical Research Ethics Committee approved (Approval No: 292) this study and obtained informed consent from both patients and controls.

Destekleyen Kurum

This study was supported by Afyonkarahisar Health Sciences University Scientific Research Projects Coordination Unit project number 22.GENEL.023.

Proje Numarası

22.GENEL.023

Kaynakça

• 1. World Health Organization. Breast cancer 13 March 2024 [Available from: https://www.who.int/news-room/fact-sheets/detail/breast-cancer.
• 2. Fielder GC, Yang TW, Razdan M, Li Y, Lu J, Perry JK, et al. The GDNF Family: A Role in Cancer? Neoplasia. 2018;20(1):99-117.
• 3. Skaper SD. Neurotrophic Factors: An Overview. In: Skaper SD, editor. Neurotrophic Factors: Methods and Protocols. New York, NY: Springer New York; 2018. p. 1-17.
• 4. Zhu S, Li Y, Bennett S, Chen J, Weng IZ, Huang L, et al. The role of glial cell line-derived neurotrophic factor family member artemin in neurological disorders and cancers. Cell Proliferation. 2020;53(7):e12860.
• 5. Banerjee A, Qian P, Wu ZS, Ren X, Steiner M, Bougen NM, et al. Artemin stimulates radio- and chemo-resistance by promoting TWIST1-BCL-2-dependent cancer stem cell-like behavior in mammary carcinoma cells. Journal of Biological Chemistry. 2012;287(51):42502-15.
• 6. Gardaneh M, Shojaei S, Kaviani A, Behnam B. GDNF induces RET-SRC-HER2-dependent growth in trastuzumab-sensitive but SRC-independent growth in resistant breast tumor cells. Breast Cancer Research and Treatment. 2017;162(2):231-41.
• 7. Milbrandt J, de Sauvage FJ, Fahrner TJ, Baloh RH, Leitner ML, Tansey MG, et al. Persephin, a novel neurotrophic factor related to GDNF and neurturin. Neuron. 1998;20(2):245-53.
• 8. Khan, M.S., Mudassar, S. (2021). Thyroid Cancer and SNPs. In: Sameer, A.S., Banday, M.Z., Nissar, S. (eds) Genetic Polymorphism and cancer
• 9. Tural S, Yuce M, A KP, Tekcan E, Celik BZ, Karabacak U, et al. Novel RET Proto-oncogene variants identified in Turkish patients with thyroid carcinoma. Gene. 2020;746:144611.
• 10. Sosonkina N, Hong SK, Starenki D, Park JI. Kinome sequencing reveals RET G691S polymorphism in human neuroendocrine lung cancer cell lines. Genes Genomics. 2014;36(6):829-41.
• 11. Siqueira DR, Ceolin L, Ferreira CV, Romitti M, Maia SC, Maciel LM, et al. Role of RET genetic variants in MEN2-associated pheochromocytoma. European Journal of Endocrinology. 2014;170(6):821-8.
• 12. Barr J, Amato CM, Robinson SE, Kounalakis N, Robinson WA. The RET G691S polymorphism is a germline variant in desmoplastic malignant melanoma. Melanoma Research. 2012;22(1):92-5.
• 13. Gil L, Azañedo M, Pollán M, Cristobal E, Arribas B, García-Albert L, et al. Genetic analysis of RET, GFR alpha 1 and GDNF genes in Spanish families with multiple endocrine neoplasia type 2A. Int J Cancer. 2002 May 10;99(2):299–304.
• 14. Cebrian A, Lesueur F, Martin S, Leyland J, Ahmed S, Luccarini C, et al. Polymorphisms in the initiators of RET (rearranged during transfection) signaling pathway and susceptibility to sporadic medullary thyroid carcinoma. Journal of Clinical Endocrinology & Metabolism. 2005;90(11):6268-74.
• 15. Fernandez RM, Ruiz-Ferrer M, Lopez-Alonso M, Antiñolo G, Borrego S. Polymorphisms in the genes encoding the 4 RET ligands, GDNF, NTN, ARTN, PSPN, and susceptibility to Hirschsprung disease. Journal of Pediatric Surgery. 2008;43(11):2042-7.
• 16. Taşkan T, Noori F, Kurukahvecioğlu O, Karaman N, Gönenç A. Neurturin gene IVSI-663 polymorphism but not RET variants is associated with increased risk for breast cancer. Laboratory Medicine. 2024;56(4):351-59.