Associated of Variable Number Tandem Repeat (VNTR) Polymorphism in IL 4 with Susceptibility to Breast Cancer in Iraqi Women

Noorhan Ihsan Oun; Maan Hasan Salih

doi:10.55544/jrasb.3.1.16

Authors

Noorhan Ihsan Oun Department of Biology, College of Science, Tikrit University, IRAQ.
Maan Hasan Salih Department of Biology, College of Science, Tikrit University, IRAQ.

DOI:

https://doi.org/10.55544/jrasb.3.1.16

Keywords:

breast cancer, IL-4, genetic variation, VNTR

Abstract

Background: Breast cancer (BC) is common disease in the worldwide. Furthermore genetic mutations are known to enhance BC risk. The aim of this research is to examine correlation between the frequency of BC among Iraqi women and a variable number tandem repeat (VNTR) polymorphism in the IL-4 gene.

Methods: The study included 74 patients and 54 healthy women. To determine the genotypes of the variable number of tandem repeats (VNTR) in the IL-4 gene, a Polymerase Chain Reaction (PCR) technique was employed. Additionally, a complete blood count (CBC) test was conducted. Logistic regression analyses were performed to evaluate the association between genotypes and the occurrence of BC. Measures of association were computed in the form of odds ratios (OR) and 95% confidence intervals (95% CI). The threshold for statistical significance in both CBC analysis and genotyping analysis was established as a p-value below 0.05.

Results: Among the CBC analysis, only the results of RBC (red blood cell count) and WBC (white blood cell count) showed statistical significance at the p = 0.05 level when comparing the study population. However, our investigation identified no association between IL-4 gene variant genotypes and breast cancer in Iraqi women. Other than tumor differentiation and body mass index(p < 0.05), no clinical or pathological features of BC patients were linked to variant genotypes.

Conclusion: The study concluded a substantial RBC and WBC relationship between patients and control. However, the IL-4 genetic variation does not appear to affect breast cancer development or progression. However, the IL-4 genetic variation may affect disease prognosis. Thus, more research is needed to determine how IL-4 genetic variation affects breast cancer prognosis.

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References

Smolarz, B., Zadrożna Nowak, A., & Romanowicz, H. Breast Cancer—Epidemiology, Classification, Pathogenesis and Treatment (Review of Literature). In Cancers .(2022). (Vol. 14, Issue 10). MDPI.

Giaquinto, A. N., Miller, K. D., Tossas, K. Y., Winn, R. A., Jemal, A., & Siegel, R. L.. Cancer statistics for African American/Black People (2022). CA: A Cancer Journal for Clinicians, 72(3).

Global Cancer Statistics: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, (2020). 71(3).

Admoun, C., & Mayrovitz, H. N. The Etiology of Breast Cancer. In Breast Cancer. (2022).

Saadeh, S., & Abdel-Razeq, H. Breast Cancer in the Arab World. In Cancer in the Arab World. (2022).

Duan, J., Pan, L., & Yang, M. Preoperative elevated neutrophil-to-lymphocyte ratio (NLR) and derived NLR are associated with poor prognosis in patients with breast cancer A meta-analysis. In Medicine (United States) (2018). (Vol. 97, Issue 49). Lippincott Williams and Wilkins. https://doi.org/10.1097/MD.0000000000013340

Ethier, J. L., Desautels, D., Templeton, A., Shah, P. S., & Amir, E. Prognostic role of neutrophil-to-lymphocyte ratio in breast cancer: A systematic review and meta-analysis. Breast Cancer Research, (2017). 19(1). https://doi.org/10.1186/s13058-016-0794-1

Guo, W., Lu, X., Liu, Q.,et al. Prognostic value of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for breast cancer patients: An updated meta-analysis of 17079 individuals. Cancer Medicine, (2019). 8(9), 4135–4148. https://doi.org/10.1002/cam4.2281

Li, X., Dai, D., Chen, B., Tang, H., Xie, X., & Wei, W. Clinicopathological and prognostic significance of cancer antigen 15-3 and carcinoembryonic antigen in breast cancer: A Meta-Analysis including 12,993 Patients. In Disease Markers (2018). (Vol. 2018). Hindawi Limited. https://doi.org/10.1155/2018/9863092

Zhang B, Beeghly-Fadiel A, Long J, Zheng W. Genetic variants associated with breast cancer risk: comprehensive field synopsis, meta-analysis, and epidemiologic evidence. Lancet Oncol. 2011;12 (5):477–488.

Han MR, Zheng W, Cai Q, et al. Evaluating genetic variants associated with breast cancer risk in high and moderate-penetrance genes in Asians. Carcinogenesis. 2017;38(5):511–518.

Leclerc M, Neuhausen SL, Schayek H, Laitman Y, Antonis AC, Friedman E. Are VNTRs co-localizing with breast cancer-associated SNPs? Breast Cancer Res Treat. 2017;168(1):277–281. doi:10.1007/ s10549-017-4588-7

Nagashima, H., Petermann, F., Pękowska, A., Chaitankar, V., Kanno, Y., & O’Shea, J. J. (2022). Remodeling of Il4-Il13-Il5 locus underlies selective gene expression. bioRxiv, 2022-07.‏ 14-

Zhao, Xin, et al. "Saikosaponin A inhibits breast cancer by regulating Th1/Th2 balance." Frontiers in Pharmacology 10 (2019): 624.‏

Giri, Prashant S., et al. "Genetic association of interleukin-4 VNTR polymorphism with susceptibility to rheumatoid arthritis in South Gujarat population." Gene Reports 25 (2021): 101322.‏

Zhu, Lu, et al. "Polymorphisms in the interleukin 4 promoter-589C/T gene and the risk of asthma: A systematic review and meta-analysis." Translational Pediatrics 10.9 (2021): 2355.‏

Hosseini-Farahabadi S, Tavakkol-Afshari J, Rafatpanah H, Farid Hosseini R, Khaje Daluei M. Association between the polymorphisms of IL-4 gene promoter (−590C>T), IL-13 coding region (R130Q) and IL-16 gene promoter (−295T>C) and allergic asthma. Iran J Allergy Asthma Immunol. 2007;6(1):9–14. doi:06.01/ijaai.914

Isidoro-García M, Dávila I, Laffond E, Moreno E, Lorente F, González-Sarmiento R. Interleukin-4 (IL4) and interleukin-4 receptor (IL4RA) polymorphisms in asthma: a case control study. Clin Mol Allergy. 2005;29:3–15.

Kok Y, Ong H, Say Y. Interleukin-1 receptor antagonist and interleukin- 4 genes variable number tandem repeats are associated with adiposity in Malaysian subjects. J Obes. 2017;1–8. doi:10.1155/2017/4104137

Park, Byoungjin, et al. "Association of white blood cell count with breast cancer burden varies according to menopausal status, body mass index, and hormone receptor status: a case-control study." Scientific Reports 9.1 (2019): 5762.‏

Okuturlar, Y. et al. Utility of peripheral blood parameters in predicting breast cancer risk. Asian Pac J Cancer Prev 16, 2409–2412 (2015).

Chen, Li, et al. "The research progress on the prognostic value of the common hematological parameters in peripheral venous blood in breast cancer." OncoTargets and Therapy (2020): 1397-1412.‏

Divsalar, Bita, et al. "Hematological Parameters Changes in Patients with Breast Cancer." Clinical Laboratory 8 (2021).‏

Shilpa, M. D., Kalyani, R., & Sreeramulu, P. N. Prognostic value of pre-treatment routine hematological parameters in breast carcinoma: Advantageous or deleterious? Biomedical Research and Therapy, (2020). 7(8), 3916–3920.

Bhikoo R, Srinivasa S, Yu TC, Moss D, Hill AG. Systematic review of breast cancer biology in developing countries (part 2): asian subcontinent and South East Asia. Cancers (Basel). 2011;3(2):2382–2401. doi:10.3390/cancers3022382

Youlden DR, Cramb SM, Yip CH, Baade PD. Incidence and mortality of female breast cancer in the Asia-Pacific region. Cancer Biol Med. 2014;11(2):101–115.

Al-arifi, A. A., Kumar, A., Chigurupati, S., Jawed, M., & Pandurangan, T. pretreatment variations in haematological parameters of breast cancer patients. International Journal of Pharmacy and Pharmaceutical Sciences, (2018a). 10(2), 157.

Kim, H. Y., Kim, T. H., Yoon, H. K., & Lee, A. The role of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in predicting neoadjuvant chemotherapy response in breast cancer. Journal of Breast Cancer, (2019). 22(3), 425–438.

Aynalem, M., Adem, N., Wendesson, F.,et al. Hematological abnormalities before and after initiation of cancer treatment among breast cancer patients attending at the University of Gondar comprehensive specialized hospital cancer treatment center. PLoS ONE, (2022). 17(8 August).

Liu, S., Lachapelle, J., Leung, S., Gao, D., Foulkes, W. D., & Nielsen, T. O. CD8 +lymphocyte infiltration is an independent favorable prognostic indicator in basal-like breast cancer. Breast Cancer Research, (2012). 14(2).

Al-arifi, A. A., Kumar, A., Chigurupati, S., Jawed, M., & Pandurangan, T. PRETREATMENT VARIATIONS IN HAEMATOLOGICAL PARAMETERS OF BREAST CANCER PATIENTS. International Journal of Pharmacy and Pharmaceutical Sciences, (2018b). 10(2).

McPherson K, Steel CM, Dixon JM. ABC of breast diseases. Breastcancer-epidemiology, risk factors, and genetics. BMJ. 2000;321(7261):624–628.

Waller M, Moss S, Watson J, Møller H. The effect of mammographic screening and hormone replacement therapy use on breast cancer incidence in England and Wales. Cancer Epidemiol Biomarkers Prev. 2017;16:2257–2261.

AL-Eitan et al Dovepress submit your manuscript | www.dovepress.com DovePress 206 Pharmacogenomics and Personalized Medicine 2019:12 Powered by TCPDF (www.tcpdf.org)

Liu, Wei, et al. "Association of polymorphisms in Th1/Th2-related cytokines (IFN-γ, TGFβ1, IL-1β, IL-2, IL-4, IL-18) with oral lichen planus: A pooled analysis of case–control studies." Journal of Dental Sciences 18.2 (2023): 560-566.‏

Apostolou P, Fostira F. Hereditary breast cancer: the era of new susceptibility genes. Biomed Res Int. 2013;2013:747318. doi:10.1155/2013/ 747318

Duan Y, Pan C, Shi J, Chen H, Zhang S. Association between interleukin-4 gene intron 3 VNTR polymorphism and cancer risk. Cancer Cell Int. 2014;14(1):131. doi:10.1186/1475-2867-14-67

Preacher KJ [Internet]. Calculation for the chi-square test: an interactive calculation tool for chi-square tests of goodness of fit and independence. 2001 [Computer software]. Available from: http:// quantpsy.org. Accessed August 09, 2019

Al-Eitan, Laith N., et al. "The influence of an IL-4 variable number tandem repeat (VNTR) polymorphism on breast cancer susceptibility." Pharmacogenomics and Personalized Medicine (2019): 201-207.‏

Serin, Istemi, et al. "Role of cytokines in multiple myeloma: IL-1RN and IL-4 VNTR polymorphisms." Cytokine 153 (2022): 155851.‏

Li, Ying, et al. "Association of inflammation-related gene polymorphisms with susceptibility and radiotherapy sensitivity in head and neck squamous cell carcinoma patients in northeast China." Frontiers in Oncology 11 (2021): 651632.‏

Vasudevan R, Norhasniza MN, Patimah I. Association of variablenumber of tandem repeats polymorphism in the IL-4 gene with endstagerenal disease in Malaysian patients. Genet Mol Res. 2011;10(2):943–947. doi:10.4238/vol10-2gmr106

POLAT, Fikriye, Günsel BİNGÖL, and Songül BUDAK DİLER. "Association of IL-4 and IL-1 Ra Gene Polymorphisms with the Risk of Bladder Cancer." Journal of the Institute of Science and Technology 12.3 (2022): 1336-1344.‏

Udina, Irina, et al. "Molecular Genetic Study on VNTR-polymorphism of Two Cytokine Genes Antagonist of the Receptor of Interleukin 1 (rs2234663) and Interleukin 4 (rs8179190) Associated with Dental Caries in Children." OBM Genetics 6.2 (2022): 1-16.‏

Walther, Kay-Arne, et al. "The Role of Polymorphisms at the Interleukin-1, Interleukin-4, GATA-3 and Cyclooxygenase-2 Genes in Non-Surgical Periodontal Therapy." International Journal of Molecular Sciences 23.13 (2022): 7266.‏

Shekari M, Kordi-Tamandani DM, MalekZadeh K, Sobti RC, Karimi S, Suri V. Effect of anti-inflammatory (IL-4, IL-10) cytokine genes in relation to risk of cervical carcinoma. Am J Clin Oncol. 2012;35(6):514–519. doi:10.1097/ COC.0b013e31822d9c12

Ibrahimi M, Jamalzei B, Akbari ME, et al. Association between interleukin 4 (IL-4) VNTR, gene polymorphism, and breast cancer susceptibility in Iranian population: experimental and web base analysis. Bratisl Lek Listy. 2018;119(10):651–654. doi:10.4149/ BLL_2018_116

Jia Y, Xie X, Shi X, Li S. Associations of common IL-4 gene polymorphisms with cancer risk: a meta-analysis. Mol Med Rep. 2017;16(2):1927–1945.

Zhao, Jingjing, et al. "Changes in plasma IL-1β, TNF-α and IL-4 levels are involved in chemotherapy-related cognitive impairment in early-stage breast cancer patients." American Journal of Translational Research 12.6 (2020): 3046.‏

Myers JS. The possible role of cytokines in chemotherapy-induced cognitive deficits. In: raffa rb, tallarida rj, editors. Chemo fog: cancer chemotherapy-related cognitive impariment. 2010. pp. 119-123.

Harry GJ and Kraft AD. Neuroinflammation and microglia: considerations and approaches for neurotoxicity assessment. Expert Opin Drug Metab Toxicol 2008; 4: 1265-77.