Abstract
Aim: Endometrial cancer is the sixth most frequent malignancy in women worldwide. Chemokines are tiny cytokines that are produced to enable different cell types to migrate in different directions. They are crucial for a number of physiological functions, including immunological responses, wound healing, and the development of cancer. Our study aimed to determine the association between CCL11 rs16969415 and CCR3 gene rs4987053 variants and the risk of endometrial cancer.
Methods: Ninety healthy controls and ninety endometrial cancer patients participated in this case-control research. Blood samples were used to obtain genomic DNA, and the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method was used to determine genotypes.
Results: The CCL11 gene rs16969415 and the CCR3 gene rs4987053 genotype distributions and allele frequencies were found to differ substantially between the patient and control groups (respectively p<0.001, p<0.05).
Conclusions: As a conclusion, the CCL11 rs16969415 and CCR3 rs4987053 variations were determined to be closely associated with endometrial cancer risk.
Keywords
Ethical Statement
This study approved by the Eskisehir Osmangazi University Non-Interventional Clinical Research Ethics Committee (Approval no: 2023/13).
Supporting Institution
Research Foundation of TÜBİTAK (Grant Number, 1919B012214687.)
Project Number
1919B012214687
Thanks
We express our gratitude to the volunteers who participated in the study.
References
- Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-49.
- Mäenpää J. Epidemiology, risk factors, and prevention for endometrial cancer. Manag of Endometrial Cancer. 2020;61-7.
- Shi J, Kraft P, Rosner BA, et al. Risk prediction models for endometrial cancer: development and validation in an international consortium. J Natl Cancer Inst. 2023;115(5):552-9.
- Crosbie EJ, Kitson SJ, McAlpine JN, Mukhopadhyay A, Powell ME, Singh N. Endometrial cancer. Lancet. 2022;399(10333):1412-28.
- Paleari L, Pesce S, Rutigliani M, et al. New Insights into Endometrial Cancer. Cancers (Basel). 2021;13(7):1496.
- Bafligil C, Thompson DJ, Lophatananon A, et al. Association between genetic polymorphisms and endometrial cancer risk: a systematic review. J Med Genet. 2020;57(9):591-600.
- O’Mara TA, Crosbie EJ. Polygenic risk score opportunities for early detection and prevention strategies in endometrial cancer. Br J Cancer. 2020;123(7):1045-6.
- Propper DJ, Balkwill FR. Harnessing cytokines and chemokines for cancer therapy. Nat Rev Clin Oncol. 2022;19(4):237-53.
- Jia SN, Han YB, Yang R, Yang ZC. Chemokines in colon cancer progression. Semin Cancer Biol. 2022;86(Pt 3):400-7.
- Ozga AJ, Chow MT, Luster AD. Chemokines and the immune response to cancer. Immunity. 2021;54(5):859-74.
- Kang WS, Kim YJ, Park HJ, Kim SK, Paik JW, Kim JW. Association of CCL11 promoter polymorphisms with schizophrenia in a Korean population. Gene. 2018;656:80-5.
- Raby BA, Van Steen K, Lazarus R, Celedón JC, Silverman EK, Weiss ST. Eotaxin polymorphisms and serum total IgE levels in children with asthma. J Allergy Clin Immunol. 2006;117(2):298-305.
- Fukunaga K, Asano K, Mao XQ, et al. Genetic polymorphisms of CC chemokine receptor 3 in Japanese and British asthmatics. Eur Respir J. 2001;17(1):59-63.
- Nolen BM, Lokshin AE. Targeting CCL11 in the treatment of ovarian cancer. Expert Opin Ther Targets. 2010;14(2):157-67.
- Corrêa LHFC. Polymorphisms in CCL5 and CCL11 genes associated with respiratory complications in children with sickle cell anemia. Repos. 2013.
- Kochetova OV, Avzaletdinova DS, Morugova TV, Mustafina OE. Chemokine gene polymorphisms association with increased risk of type 2 diabetes mellitus in Tatar ethnic group, Russia. Mol Biol Rep. 2019;46(1):887-96.
- Yagci E, Kurt H, Ozen A, Ozbayer C, Colak E. Inflammatory Gene Variants and Protein Levels: An Important Predictor of Prostate Cancer Development. J Environ Pathol Toxicol Oncol. 2025.
- Breunis WB, Biezeveld MH, Geissler J, et al. Polymorphisms in chemokine receptor genes and susceptibility to Kawasaki disease. Clin Exp Immunol. 2007;150(1):83-90.
- Goode EL, Maurer MJ, Sellers TA, et al. Inherited determinants of ovarian cancer survival. Clin Cancer Res. 2010;16(3):995-1007.
- Qin R, Ren W, Ya G, et al. Role of chemokines in the crosstalk between tumor and tumor-associated macrophages. Clin Exp Med. 2023;23(5):1359-73.
Abstract
Amaç: Endometrium kanseri dünya çapında kadınlarda en sık görülen altıncı malignitedir. Kemokinler, hücrelerin farklı yönlere göç etmesine neden olmak için üretilen küçük sitokinlerdir. İmmünolojik tepkiler, yara iyileşmesi ve kanser gelişimi gibi fizyolojik işlevler için çok önemlidirler. Çalışmamızın amacı CCL11 rs16969415 ve CCR3 geni rs4987053 varyantları ile endometrial kanser riski arasındaki ilişkiyi belirlemektir.
Yöntemler: Bu vaka-kontrol araştırmasına doksan sağlıklı kontrol ve doksan endometrial kanser hastası katılmıştır. Genomik DNA elde etmek için kan örnekleri kullanılmış ve genotipleri belirlemek için Polimeraz Zincir Reaksiyonu-Restriksiyon Fragment Uzunluk Polimorfizmi (PCR-RFLP) yöntemi kullanılmıştır.
Bulgular: CCL11 geni rs16969415 ve CCR3 geni rs4987053 genotip dağılımları ve alel frekanslarının hasta ve kontrol grupları arasında önemli ölçüde farklılık gösterdiği bulunmuştur (sırasıyla p<0,001, p<0,05).
Sonuç: Sonuç olarak CCL11 rs16969415 ve CCR3 rs4987053 varyasyonlarının endometrium kanseri riski ile yakın ilişkili olduğu belirlendi.
Keywords
Project Number
1919B012214687
References
- Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-49.
- Mäenpää J. Epidemiology, risk factors, and prevention for endometrial cancer. Manag of Endometrial Cancer. 2020;61-7.
- Shi J, Kraft P, Rosner BA, et al. Risk prediction models for endometrial cancer: development and validation in an international consortium. J Natl Cancer Inst. 2023;115(5):552-9.
- Crosbie EJ, Kitson SJ, McAlpine JN, Mukhopadhyay A, Powell ME, Singh N. Endometrial cancer. Lancet. 2022;399(10333):1412-28.
- Paleari L, Pesce S, Rutigliani M, et al. New Insights into Endometrial Cancer. Cancers (Basel). 2021;13(7):1496.
- Bafligil C, Thompson DJ, Lophatananon A, et al. Association between genetic polymorphisms and endometrial cancer risk: a systematic review. J Med Genet. 2020;57(9):591-600.
- O’Mara TA, Crosbie EJ. Polygenic risk score opportunities for early detection and prevention strategies in endometrial cancer. Br J Cancer. 2020;123(7):1045-6.
- Propper DJ, Balkwill FR. Harnessing cytokines and chemokines for cancer therapy. Nat Rev Clin Oncol. 2022;19(4):237-53.
- Jia SN, Han YB, Yang R, Yang ZC. Chemokines in colon cancer progression. Semin Cancer Biol. 2022;86(Pt 3):400-7.
- Ozga AJ, Chow MT, Luster AD. Chemokines and the immune response to cancer. Immunity. 2021;54(5):859-74.
- Kang WS, Kim YJ, Park HJ, Kim SK, Paik JW, Kim JW. Association of CCL11 promoter polymorphisms with schizophrenia in a Korean population. Gene. 2018;656:80-5.
- Raby BA, Van Steen K, Lazarus R, Celedón JC, Silverman EK, Weiss ST. Eotaxin polymorphisms and serum total IgE levels in children with asthma. J Allergy Clin Immunol. 2006;117(2):298-305.
- Fukunaga K, Asano K, Mao XQ, et al. Genetic polymorphisms of CC chemokine receptor 3 in Japanese and British asthmatics. Eur Respir J. 2001;17(1):59-63.
- Nolen BM, Lokshin AE. Targeting CCL11 in the treatment of ovarian cancer. Expert Opin Ther Targets. 2010;14(2):157-67.
- Corrêa LHFC. Polymorphisms in CCL5 and CCL11 genes associated with respiratory complications in children with sickle cell anemia. Repos. 2013.
- Kochetova OV, Avzaletdinova DS, Morugova TV, Mustafina OE. Chemokine gene polymorphisms association with increased risk of type 2 diabetes mellitus in Tatar ethnic group, Russia. Mol Biol Rep. 2019;46(1):887-96.
- Yagci E, Kurt H, Ozen A, Ozbayer C, Colak E. Inflammatory Gene Variants and Protein Levels: An Important Predictor of Prostate Cancer Development. J Environ Pathol Toxicol Oncol. 2025.
- Breunis WB, Biezeveld MH, Geissler J, et al. Polymorphisms in chemokine receptor genes and susceptibility to Kawasaki disease. Clin Exp Immunol. 2007;150(1):83-90.
- Goode EL, Maurer MJ, Sellers TA, et al. Inherited determinants of ovarian cancer survival. Clin Cancer Res. 2010;16(3):995-1007.
- Qin R, Ren W, Ya G, et al. Role of chemokines in the crosstalk between tumor and tumor-associated macrophages. Clin Exp Med. 2023;23(5):1359-73.
Details
| Primary Language | English |
|---|---|
| Subjects | Medical Genetics (Excl. Cancer Genetics) |
| Journal Section | ORIGINAL ARTICLE |
| Authors | |
| Project Number | 1919B012214687 |
| Publication Date | May 29, 2025 |
| Submission Date | December 9, 2024 |
| Acceptance Date | March 10, 2025 |
| Published in Issue | Year 2025 Volume: 30 Issue: 2 |
This Journal licensed under a CC BY-NC (Creative Commons Attribution-NonCommercial 4.0) International License.