Angiogenesis, Inflammation & Therapeutics | Online ISSN  2207-872X
RESEARCH ARTICLE   (Open Access)

Effect of Toll-Like Receptor 9 (TLR9) in Breast Cancer Risk, Along with Hormonal Effects in Patients Receiving Radiotherapy

Asra'a Adnan Abdul-Jalil 1, Marrib N. Rasheed 2, Rana H. Hamoode 3

+ Author Affiliations

Journal of Angiotherapy 8 (1) 1-7 https://doi.org/10.25163/angiotherapy.819424

Submitted: 12 December 2023 Revised: 17 January 2024  Published: 18 January 2024 


Abstract

Introduction: Antioxidant enzyme polymorphisms and innate immune receptors have been implicated in the development of various cancer forms. This study aimed to assess the potential association between toll-like receptor 9 (TLR9) polymorphisms and female susceptibility to breast cancer. Methods: Forty female breast cancer patients from Iraq and 20 healthy volunteers were enrolled in the study. Gene polymorphisms of TLR9 rs187084 (1237T/C) were analyzed using real-time polymerase chain reaction (RT-PCR). Additionally, a hormonal study was conducted, comparing breast cancer patients exposed to radiation with a control group. The levels of follicle-stimulating hormone (FSH), estradiol (E2), and progesterone were measured. Results: The analysis revealed a non-significant increase in the prevalence of TLR9 wild TT genotypes among breast cancer patients compared to healthy individuals (72.5% vs. 90%, respectively). Conversely, heterozygous CT genotypes were significantly higher in breast cancer patients compared to healthy women (22.5% vs. 10%, P<0.05). In the hormonal study, breast cancer patients exposed to radiation exhibited a significant increase in FSH levels (2.9 vs. 18.8 IU/ml), a significant decrease in E2 levels (0.232 vs. 0.910 pico/ml), and a significant increase in progesterone levels (0.910 vs. 0.732 nanogram/ml).  Conclusion: The study concludes that TLR9 rs187084 (1237T/C) polymorphism variants play crucial roles in the susceptibility of Iraqi females to breast cancer. Furthermore, the observed hormonal disruptions in FSH, E2, and progesterone levels highlight potential contributors to breast cancer development, emphasizing the need for further exploration of genetic and hormonal factors in cancer susceptibility.

Keywords: Antioxidant enzyme polymorphisms, Toll-like receptor 9 (TLR9) polymorphisms, Breast cancer susceptibility, Hormonal disruptions, Genetic and hormonal factors

References


Ashton, K. A., Proietto, A., Otton, G., Symonds, I., McEvoy, M., Attia, J., & Scott, R. J. (2010). Toll-like receptor (TLR) and nucleosome-binding oligomerization domain (NOD) gene polymorphisms and endometrial cancer risk. BMC cancer, 10(1), 1-7.‏

Chen FC, Oskay-Ozcelik G, Bühling KJ, et al. (2009). Prognostic value of serum and ascites levels of estradiol, FSH, LH and prolactin in ovarian cancer. Anticancer Res. ;29:1575–1578.

Chimento, A., Luca, A. De, Avena, P., Amicis, F. De, Casaburi, I., & Sirianni, R. (2022). Estrogen Receptors-Mediated Apoptosis in HormoneDependent Cancers.

Choi JH, Choi KC, Auersperg N, Leung PC. (2004). Overexpression of follicle-stimulating hormone receptor activates oncogenic pathways in preneoplastic ovarian surface epithelial cells. J Clin Endocrinol Metab;89:5508–5516.

Chrusciel M, Ponikwicka-Tyszko D, Wolczynski S, Huhtaniemi I and Rahman NA (2019) Extragonadal FSHR Expression and Function—Is It Real? Front. Endocrinol. 10:32.

Ciruelos Gil, E. M. (2014). Targeting the PI3K/AKT/mTOR pathway in estrogen receptorpositive breast cancer. Cancer Treatment Reviews, 40(7), 862–871. https://doi.org/10.1016/j.ctrv.2014.03.004.

 

Daniel AR, Faivre EJ, Lange CA. (2007). Phosphorylation-dependent antagonism of sumoylation de-represses progesterone receptor action in breast cancer cells. Mol Endocrinol. 21(12):2890–906.

Daniel AR, Qiu M, Faivre EJ, Ostrander JH, Skildum A, Lange CA. (2007). Linkage of progestin and epidermal growth factor signaling: phosphorylation of progesterone receptors mediates transcriptional hypersensitivity and increased ligand-independent breast cancer cell growth. Steroids.  72(2):188–201.

Eduardo O.; Paola C.; Jorlana S. (2016). Association between the glutathione S-transferase P1 (GSTP1) Ile105Val gene polymorphism in obese and overweight patients over 60 years. J Bras Patol Med Lab, 52(4), p. 211-216.

Eskelinen M., Nordén T., Lindgren A., Wide L., Adami H.O., Holmberg L (2004). Preoperative serum levels of follicle stimulating hormone (FSH) and prognosis in invasive breast cancer. European Journal of Surgical Oncology (EJSO); 30(5): 495-500.

 Ferlay, J., Soerjomataram, I., Dikshit, R., Eser, S., Mathers, C., Rebelo, M. & Bray, F. (2015). Cancer incidence and mortality worldwide: sources, methods and major patterns in Globocan 2012. International journal of cancer, 136(5), 359-386.‏

Howard, J. H., & Bland, K. I. (2012). Current management and treatment strategies for breast cancer. Current Opinion in obstetrics and gynecology, 24(1), 44-48.‏

Huhtaniemi I. (2010). Are gonadotrophins tumorigenic - a critical review of clinical and experimental data. Mol Cell Endocrinol;329:56–61.

Hunzicker-Dunn M, Maizels ET. (2006). FSH signaling pathways in immature granulosa cells that regulate target gene expression: branching out from protein kinase A. Cell Signal.;18:1351–1359.

Ilvesaro, J. M., Merrell, M. A., Li, L., Wakchoure, S., Graves, D., Brooks, S., ... & Selander, K. S. (2008). Toll-like receptor 9 mediates CpG oligonucleotide–induced cellular invasion. Molecular Cancer Research, 6(10), 1534-1543.‏

Itano, J.K., Brant, J., Conde, F. and Saria, M. (2015). Breast Cancer. In: Core Curriculum for Oncology Nursing. 5th edition. Elsevier Health Sciences, Philadelphia, PA, pp75.

Jung, J.; Yoo, S. (2023) Identification of Breast Cancer Metastasis Markers from Gene Expression Profiles Using Machine Learning Approaches. Genes, 14, 1820. https://doi.org/10.3390/genes14091820.

 

Klaunig, J. E., Kamendulis, L. M., & Hocevar, B. A. (2010). Oxidative stress and oxidative damage in carcinogenesis. Toxicologic pathology, 38(1), 96-109.‏

Knutson, T.P., Truong, T.H., Ma, S. et al.( 2017). Posttranslationally modified progesterone receptors direct ligand-specific expression of breast cancer stem cell-associated gene programs. J Hematol Oncol 10, 89 .

Lange CA, Gioeli D, Hammes SR, Marker PC. (2007). Integration of rapid signaling events with steroid hormone receptor action in breast and prostate cancer. Annu Rev Physiol. 69:171–199.

Latz, E., Schoenemeyer, A., Visintin, A., Fitzgerald, K. A., Monks, B. G., Knetter, C. F. & Golenbock, D. T. (2004). TLR9 signals after translocating from the ER to CpG DNA in the lysosome. Nature immunology, 5(2), 190-198

Lindsay R., Gallagher J.C., Kleerekoper U. and Pickar J.H. (2002). “Effect of lower doses of estrogen therapy for postmenopausal women”. Jama Middle East, 12(9): pp.74-84

Marquez-Lago, T.T., Steinberg, S. (2022). Stochastic model of ERK-mediated progesterone receptor translocation, clustering and transcriptional activity. Sci Rep 12, 11791.

Medvedev, A. E. (2013). Toll-like receptor polymorphisms, inflammatory and infectious diseases, allergies, and cancer. Journal of Interferon & Cytokine Research, 33(9), 467-484.‏

Neyman A, Eugster EA. (2017). Treatment of Girls and Boys with McCune-Albright Syndrome with Precocious Puberty - Update 2017. Pediatr Endocrinol Rev.  Dec;15(2):136-141.

Novak, N., Yu, C. F., Bussmann, C., Maintz, L., Peng, W. M., Hart, J. & Weidinger, S. (2007). Putative association of a TLR9 promoter polymorphism with atopic eczema. Allergy, 62(7), 766-772.‏

Pljesa-Ercegovac, M.; Savic-Radojevic, A.; Matic, M.; Coric, V.; Djukic, T.; Radic, T.; Simic, T.( 2018). Glutathione Transferases: Potential Targets to Overcome Chemoresistance in Solid Tumors. Int. J. Mol. Sci. , 19, 3785. 

Rasheed M. N. Hamoode R. H and Abdul-Jalil A. A. (2022). Association of glutathione S-transferase 1 (GSTP1) polymorphisms with Breast Cancer susceptibility. Volume 7 / Issue 3 / 41 / http://dx.doi.org/10.21931/RB/2022.07.41

 

Roszak, A., Lianeri, M., Sowinska, A., & Jagodzinski, P. P. (2012). Involvement of Toll-like Receptor 9 polymorphism in cervical cancer development. Molecular biology reports, 39(8), 8425-8430.‏

Ulrich, C. M., Robien, K., & McLeod, H. L. (2003). Cancer pharmacogenetics: polymorphisms, pathways and beyond. Nature Reviews Cancer, 3(12), 912-920.‏

Wayne CM, Fan HY, Cheng X, Richards JS. (2007). Follicle-stimulating hormone induces multiple signaling cascades: evidence that activation of Rous sarcoma oncogene, RAS, and the epidermal growth factor receptor are critical for granulosa cell differentiation. Mol Endocrinol. 21:1940–1957.

Zhang, B. L., Tong, S. U. N., Zhang, B. N., Zheng, S., Ning, L. Ü., Xu, B. H. & Lin, D. X. (2011). Polymorphisms ofGSTP1is associated with differences of chemotherapy response and toxicity in breast cancer. Chinese medical journal, 124(2), 199-204.‏

PDF
Abstract
Export Citation

View Dimensions


View Plumx


View Altmetric




Save
0
Citation
559
View

Share