Abstract
Amaç: Tümör nekroz faktör-alfa (TNF-α), nekroz veya apoptoza yol açan çeşitli sinyal yolaklarında, inflamatuvar ve otoimmün hastalıkların patogenezinde rol oynamaktadır. TNF-α genindeki rs1800629 polimorfizmi G>A değişimi yaparak genin ifade seviyelerini etkiler. TNF-α -308G alleli ile karşılaştırıldığında, A alleli daha yüksek transkripsiyonel aktiviteye sahiptir. IKZF1 geni ise, hücre döngüsünün ilerlemesini ve hücre sağkalımını kontrol eden genlerin ekspresyonunu düzenleyen transkripsiyon faktörü IKAROS'u kodlamaktadır. IKZF1 geni, kromatinin yeniden şekillenmesi ile ilişkili çinko parmak DNA bağlayıcı proteinler ailesindendir. Bu protein lenfosit diferansiasyonunun da düzenleyicisidir. IKZF1 genindeki rs4132601 polimorfizminin T/G değişimi yaparak genin ekspresyon seviyesini etkilediği ve otoimmün hastalıklar ve lenfoma ile ilişkili olduğu bulunmuştur. TNF-α ile IKZF1 gen polimorfizmlerinin Hodgkin lenfoma için bir risk faktörü olup olmadığını değerlendirmeyi amaçladık. Yöntem: Hodgkin lenfoma tanısı olan hasta grubu ile malignitesi olmayan kontrol grubu hastalarda TNF-α ve IKZF1gen polimorfizmleri gerçek zamanlı polimeraz zincir reaksiyon (Rt-PCR) yöntemi ile araştırılmıştır. Elde edilen veriler SPSS paket programında analiz edilmiştir. Bulgular: TNF-α (rs1800629) genindeki polimorfizmde, gruplara göre TNF-α (rs1800629) genotip ve allel dağılımlarının farklılık göstermediği saptanmıştır (p>0.05). Gruplara göre TNF-α (rs4132601) genotipler arasında farklılık göstermediği anacak allel dağılımlarının farklılık gösterdiği saptanmıştır (p=0,087), ve hasta grubunda kontrol grubuna kıyasla G alleli T alleline göre 2,34 kat daha fazla tespit edilmiştir. Sonuç: Bulgularımız, IKZF1 (rs4132601) geninde G allelinin Hodgkin lenfoma için bir risk faktörü olabileceğini göstermektedir.
Supporting Institution
Mersin Üniversitesi Bilimsel araştrma projeleri birimi
Project Number
2021-1-TP2-4148
References
- Bayırlı R, Akşit M. A. Şüphenin çözümü olgudadır; Over yerleşimli anaplastik büyük hücreli lenfoma. Türk Dünyası Uygulama ve Araştırma Merkezi Yenidoğan Dergisi, 2019 Feb 28, 4(1), 77-82.
- Ekström-Smedby K. Epidemiology and etiology of non-Hodgkin lymphoma-a review. Acta Oncol. 2006;45(3):258-271. doi:10.1080/02841860500531682
- Saarinen S, Pukkala E, Vahteristo P, Mäkinen MJ, Franssila K, Aaltonen LA. High familial risk in nodular lymphocyte-predominant Hodgkin lymphoma. J Clin Oncol. 2013;31(7):938-943. doi:10.1200/JCO.2012.43.5958
- Kanakry JA, Li H, Gellert LL, et al. Plasma Epstein-Barr virus DNA predicts outcome in advanced Hodgkin lymphoma: correlative analysis from a large North American cooperative group trial. Blood. 2013;121(18):3547-3553. doi:10.1182/blood-2012-09-454694
- Jang DI, Lee AH, Shin HY, et al. The Role of Tumor Necrosis Factor Alpha (TNF-α) in Autoimmune Disease and Current TNF-α Inhibitors in Therapeutics. Int J Mol Sci. 2021;22(5):2719. Published 2021 Mar 8. doi:10.3390/ijms22052719
- Nakayama S, Yokote T, Hirata Y, et al. TNF-α expression in tumor cells as a novel prognostic marker for diffuse large B-cell lymphoma, not otherwise specified. Am J Surg Pathol. 2014;38(2):228-234. doi:10.1097/PAS.0000000000000094
- Chouchane L, Ahmed SB, Baccouche S, Remadi S. Polymorphism in the tumor necrosis factor-alpha promotor region and in the heat shock protein 70 genes associated with malignant tumors. Cancer. 1997;80(8):1489-1496. doi:10.1002/(sici)10970142(19971015)80:8<1489:aidcncr17>3.0.co;2-1
- He YQ, Zhu JH, Huang SY, Cui Z, He J, Jia WH. The association between the polymorphisms of TNF-α and non-Hodgkin lymphoma: a meta-analysis. Tumour Biol. 2014;35(12):12509-12517. doi:10.1007/s13277-014-2569-6
- Pieper K, Grimbacher B, Eibel H. B-cell biology and development. J Allergy Clin Immunol. 2013;131(4):959-971. doi:10.1016/j.jaci.2013.01.046
- Küppers R, Engert A, Hansmann ML. Hodgkin lymphoma. J Clin Invest. 2012;122(10):3439-3447. doi:10.1172/JCI61245
- Weber-Matthiesen K, Deerberg J, Poetsch M, Grote W, Schlegelberger B. Numerical chromosome aberrations are present within the CD30+ Hodgkin and Reed-Sternberg cells in 100% of analyzed cases of Hodgkin's disease. Blood. 1995;86(4):1464-1468.
- Salati M, Cesaretti M, Macchia M, Mistiri ME, Federico M. Epidemiological Overview of Hodgkin Lymphoma across the Mediterranean Basin. Mediterr J Hematol Infect Dis. 2014;6(1):e2014048. Published 2014 Jul 1. doi:10.4084/MJHID.2014.048
- Idriss HT, Naismith JH. TNF alpha and the TNF receptor superfamily: structure-function relationship(s). Microsc Res Tech. 2000;50(3):184-195. doi:10.1002/10970029(20000801)50:3<184:AID-JEMT2>3.0.CO;2-H
- Khan S, Mandal RK, Jawed A, et al. TNF-α -308 G > A (rs1800629) Polymorphism is Associated with Celiac Disease: A Meta-analysis of 11 Case-Control Studies. Sci Rep. 2016;6:32677. Published 2016 Sep 6. doi:10.1038/srep32677
- Al-Khatib SM, Abdo N, Al-Eitan LN, Al-Mistarehi AW, Zahran DJ, Kewan TZ. LTA, LEP, and TNF-a Gene Polymorphisms are Associated with Susceptibility and Overall Survival of Diffuse Large B-Cell lymphoma in an Arab Population: A Case-Control Study. Asian Pac J Cancer Prev. 2020;21(9):2783-2791. Published 2020 Sep 1. doi:10.31557/ APJCP.2020.21.9.2783
- Mahjoub S, Chayeb V, Zitouni H, et al. IKZF1 genetic variants rs4132601 and rs11978267 and acute lymphoblastic leukemia risk in Tunisian children: a case-control study. BMC Med Genet. 2019;20(1):159. Published 2019 Oct 11. doi:10.1186/s12881-019-0900-1
- Bielska M, Borowiec M, Jesionek-Kupnicka D, et al. Polymorphism in IKZF1 gene affects clinical outcome in diffuse large B-cell lymphoma. Int J Hematol. 2017;106(6):794-800. doi:10.1007/s12185-017-2315-0
- Li S, Ren L, Fan L, Wang G. IKZF1 rs4132601 polymorphism and acute lymphoblastic leukemia susceptibility: a meta-analysis. Leuk Lymphoma. 2015;56(4):978-982. doi:10.3109/10428194.2014.939965
- Wu X, Liu M, Wang Q. IKZF1 Rs4132601 Polymorphism and Susceptibility to Acute Lymphocytic Leukemia in Children: A Meta-analysis [published online ahead of print, 2021 Mar 3]. J Pediatr Hematol Oncol. 2021;10.1097/MPH.0000000000002130. doi:10.1097/MPH.0000000000002130
- Zhai K, Ding J, Zhou Y. Different role of tumor necrosis factor-α polymorphism in non-Hodgkin lymphomas among Caucasian and Asian populations: a meta-analysis. Int J Mol Sci. 2014;15(5):7684-7698. Published 2014 May 5. doi:10.3390/ijms15057684
- Wang SS, Vajdic CM, Linet MS, et al. Associations of non-Hodgkin Lymphoma (NHL) risk with autoimmune conditions according to putative NHL loci. Am J Epidemiol. 2015;181(6):406-421. doi:10.1093/aje/kwu290
- Rothman N, Skibola CF, Wang SS, et al. Genetic variation in TNF and IL10 and risk of non-Hodgkin lymphoma: a report from the InterLymph Consortium. Lancet Oncol. 2006;7(1):27-38. doi:10.1016/S14702045(05)70434-4
- Liu J, Liu J, Song B, et al. Genetic variations in CTLA-4, TNF-α, and LTA and susceptibility to T-cell lymphoma in a Chinese population. Cancer Epidemiol. 2013;37(6):930-934. doi:10.1016/j.canep.2013.08.011
The role of TNF-α (rs1800629) ve IKZF1 (rs4132601) gen polimorphisms in pathogenesis of Hodgkin’s lymphoma
Abstract
Aim: Tumor necrosis factor-alpha (TNF-α) plays a role in various signaling pathways leading to necrosis or apoptosis and in the pathogenesis of inflammatory and autoimmune diseases. The rs1800629 polymorphism in the TNF-α gene affects the expression levels of the gene by making a G>A exchange. The IKZF1 gene encodes the transcription factor IKAROS, which regulates the expression of genes that control cell cycle permanence and cell survival. The IKZF1 gene is in the family of zinc finger DNA-binding proteins associated with chromatin remodeling. This protein is also a regulator of lymphocyte differentiation. The rs4132601 polymorphism in the IKZF1 gene affects the expression level of the gene by making a T/G exchange, and have been found to be associated with autoimmune diseases and lymphoma. We aimed to explore TNF-α and IKZF1 gene polymorphisms in patients with Hodgkin lymphoma and investigate whether we could identify them as risk factors. Method: TNF-α and IKZF1 gene polymorphisms were analyzed in patient group diagnosed with Hodgkin lymphoma and the control group without malignancy. The results were evaluated with the Chi-Square test. Data were analyzed in the Statistical Package for the Social Sciences (SPSS) program. Results: TNF-α (rs1800629) genotype and allele distributions did not differ between two groups (p>0.05). IKZF1 (rs4132601)allele distributions differed between the groups (p=0.087), and G allele was detected 2.34 times more than T allele in the patient group compared to the control group. Conclusion: Our results indicate that G allele in IKZF1 (rs4132601) gene may be a risk factor for Hodgkin lymphoma.
Project Number
2021-1-TP2-4148
References
- Bayırlı R, Akşit M. A. Şüphenin çözümü olgudadır; Over yerleşimli anaplastik büyük hücreli lenfoma. Türk Dünyası Uygulama ve Araştırma Merkezi Yenidoğan Dergisi, 2019 Feb 28, 4(1), 77-82.
- Ekström-Smedby K. Epidemiology and etiology of non-Hodgkin lymphoma-a review. Acta Oncol. 2006;45(3):258-271. doi:10.1080/02841860500531682
- Saarinen S, Pukkala E, Vahteristo P, Mäkinen MJ, Franssila K, Aaltonen LA. High familial risk in nodular lymphocyte-predominant Hodgkin lymphoma. J Clin Oncol. 2013;31(7):938-943. doi:10.1200/JCO.2012.43.5958
- Kanakry JA, Li H, Gellert LL, et al. Plasma Epstein-Barr virus DNA predicts outcome in advanced Hodgkin lymphoma: correlative analysis from a large North American cooperative group trial. Blood. 2013;121(18):3547-3553. doi:10.1182/blood-2012-09-454694
- Jang DI, Lee AH, Shin HY, et al. The Role of Tumor Necrosis Factor Alpha (TNF-α) in Autoimmune Disease and Current TNF-α Inhibitors in Therapeutics. Int J Mol Sci. 2021;22(5):2719. Published 2021 Mar 8. doi:10.3390/ijms22052719
- Nakayama S, Yokote T, Hirata Y, et al. TNF-α expression in tumor cells as a novel prognostic marker for diffuse large B-cell lymphoma, not otherwise specified. Am J Surg Pathol. 2014;38(2):228-234. doi:10.1097/PAS.0000000000000094
- Chouchane L, Ahmed SB, Baccouche S, Remadi S. Polymorphism in the tumor necrosis factor-alpha promotor region and in the heat shock protein 70 genes associated with malignant tumors. Cancer. 1997;80(8):1489-1496. doi:10.1002/(sici)10970142(19971015)80:8<1489:aidcncr17>3.0.co;2-1
- He YQ, Zhu JH, Huang SY, Cui Z, He J, Jia WH. The association between the polymorphisms of TNF-α and non-Hodgkin lymphoma: a meta-analysis. Tumour Biol. 2014;35(12):12509-12517. doi:10.1007/s13277-014-2569-6
- Pieper K, Grimbacher B, Eibel H. B-cell biology and development. J Allergy Clin Immunol. 2013;131(4):959-971. doi:10.1016/j.jaci.2013.01.046
- Küppers R, Engert A, Hansmann ML. Hodgkin lymphoma. J Clin Invest. 2012;122(10):3439-3447. doi:10.1172/JCI61245
- Weber-Matthiesen K, Deerberg J, Poetsch M, Grote W, Schlegelberger B. Numerical chromosome aberrations are present within the CD30+ Hodgkin and Reed-Sternberg cells in 100% of analyzed cases of Hodgkin's disease. Blood. 1995;86(4):1464-1468.
- Salati M, Cesaretti M, Macchia M, Mistiri ME, Federico M. Epidemiological Overview of Hodgkin Lymphoma across the Mediterranean Basin. Mediterr J Hematol Infect Dis. 2014;6(1):e2014048. Published 2014 Jul 1. doi:10.4084/MJHID.2014.048
- Idriss HT, Naismith JH. TNF alpha and the TNF receptor superfamily: structure-function relationship(s). Microsc Res Tech. 2000;50(3):184-195. doi:10.1002/10970029(20000801)50:3<184:AID-JEMT2>3.0.CO;2-H
- Khan S, Mandal RK, Jawed A, et al. TNF-α -308 G > A (rs1800629) Polymorphism is Associated with Celiac Disease: A Meta-analysis of 11 Case-Control Studies. Sci Rep. 2016;6:32677. Published 2016 Sep 6. doi:10.1038/srep32677
- Al-Khatib SM, Abdo N, Al-Eitan LN, Al-Mistarehi AW, Zahran DJ, Kewan TZ. LTA, LEP, and TNF-a Gene Polymorphisms are Associated with Susceptibility and Overall Survival of Diffuse Large B-Cell lymphoma in an Arab Population: A Case-Control Study. Asian Pac J Cancer Prev. 2020;21(9):2783-2791. Published 2020 Sep 1. doi:10.31557/ APJCP.2020.21.9.2783
- Mahjoub S, Chayeb V, Zitouni H, et al. IKZF1 genetic variants rs4132601 and rs11978267 and acute lymphoblastic leukemia risk in Tunisian children: a case-control study. BMC Med Genet. 2019;20(1):159. Published 2019 Oct 11. doi:10.1186/s12881-019-0900-1
- Bielska M, Borowiec M, Jesionek-Kupnicka D, et al. Polymorphism in IKZF1 gene affects clinical outcome in diffuse large B-cell lymphoma. Int J Hematol. 2017;106(6):794-800. doi:10.1007/s12185-017-2315-0
- Li S, Ren L, Fan L, Wang G. IKZF1 rs4132601 polymorphism and acute lymphoblastic leukemia susceptibility: a meta-analysis. Leuk Lymphoma. 2015;56(4):978-982. doi:10.3109/10428194.2014.939965
- Wu X, Liu M, Wang Q. IKZF1 Rs4132601 Polymorphism and Susceptibility to Acute Lymphocytic Leukemia in Children: A Meta-analysis [published online ahead of print, 2021 Mar 3]. J Pediatr Hematol Oncol. 2021;10.1097/MPH.0000000000002130. doi:10.1097/MPH.0000000000002130
- Zhai K, Ding J, Zhou Y. Different role of tumor necrosis factor-α polymorphism in non-Hodgkin lymphomas among Caucasian and Asian populations: a meta-analysis. Int J Mol Sci. 2014;15(5):7684-7698. Published 2014 May 5. doi:10.3390/ijms15057684
- Wang SS, Vajdic CM, Linet MS, et al. Associations of non-Hodgkin Lymphoma (NHL) risk with autoimmune conditions according to putative NHL loci. Am J Epidemiol. 2015;181(6):406-421. doi:10.1093/aje/kwu290
- Rothman N, Skibola CF, Wang SS, et al. Genetic variation in TNF and IL10 and risk of non-Hodgkin lymphoma: a report from the InterLymph Consortium. Lancet Oncol. 2006;7(1):27-38. doi:10.1016/S14702045(05)70434-4
- Liu J, Liu J, Song B, et al. Genetic variations in CTLA-4, TNF-α, and LTA and susceptibility to T-cell lymphoma in a Chinese population. Cancer Epidemiol. 2013;37(6):930-934. doi:10.1016/j.canep.2013.08.011
Details
| Primary Language | Turkish |
|---|---|
| Subjects | Health Care Administration |
| Journal Section | Articles |
| Authors | |
| Project Number | 2021-1-TP2-4148 |
| Publication Date | April 30, 2022 |
| Submission Date | November 2, 2021 |
| Acceptance Date | February 2, 2022 |
| Published in Issue | Year 2022 Volume: 15 Issue: 1 |
Cite
MEU Journal of Health Sciences Assoc was began to the publishing process in 2008 under the supervision of Assoc. Prof. Gönül Aslan, Editor-in-Chief, and affiliated to Mersin University Institute of Health Sciences. In March 2015, Prof. Dr. Caferi Tayyar Şaşmaz undertook the Editor-in Chief position and since then he has been in charge.
Publishing in three issues per year (April - August - December), it is a multisectoral refereed scientific journal. In addition to research articles, scientific articles such as reviews, case reports and letters to the editor are published in the journal. Our journal, which has been published via e-mail since its inception, has been published both online and in print. Following the Participation Agreement signed with TÜBİTAK-ULAKBİM Dergi Park in April 2015, it has started to accept and evaluate online publications.
Mersin University Journal of Health Sciences have been indexed by Turkey Citation Index since November 16, 2011.
Mersin University Journal of Health Sciences have been indexed by ULAKBIM Medical Database from the first issue of 2016.
Mersin University Journal of Health Sciences have been indexed by DOAJ since October 02, 2019.
Article Publishing Charge Policy: Our journal has adopted an open access policy and there is no fee for article application, evaluation, and publication in our journal. All the articles published in our journal can be accessed from the Archive free of charge.
This work is licensed with Attribution-NonCommercial 4.0 International.