Association between Matrix Metalloproteinas-2 Gene Variants and Pathogenesis of Breast Cancer in Sera of Iraqi Women
AbstractObjective: The current study aims to investigate the role of MMP-2 in breast cancer pathogenesis in Iraqi women.
Methods: A forty one women with breast cancer and 45 control women were included in this case-control study. Body mass index, age, smoking; married status, tumor size, degree, subtype, lymph node status, pre and postmenopesua included the phenotypic results. The polymerase chain reaction-PCR-allele specific restriction was used to observe the rs243865 polymorphism. Genomic DNA was extracted from whole blood and genotyping with specific prefixes for amplification of the MMP-2 gene was accomplished as enzyme-restricted PCR products were digested, followed by electrophoresis on 1.5% agarose gel. In order to interpret the researchers' results, numerous statistical analyses were applied.
Results: The amplicon size of MMP-2 gene was 304 bp, and following its amplification reactions by allelic specific PCR. The amplification product for MMP-2 gene amplification SNP rs243865 gene polymorphism results exhibited one band of 304 bp, two bands of 304 bp and one band 304 bp for individuals have genotype as wild type (CC), homozygous (TT) and heterozygous (CT), respectively. Genotype frequencies of rs243865 polymorphism were found to be consistent with Hardy–Weinberg equilibrium. Allele frequencies of C allele was 0.57, and the T allele was only 0.43 in cases of breast cancer women patient, while the frequencies of CC, CT, and TT genotypes of the rs243865 SNP were statistically significant as 31.7%, 51.2%, 17.1% respectively. Allele frequencies of C and T were 0.78 and 0.22 for the control group, respectively, the heterozygous genotype (CT) was significantly increased the risk of breast cancer women (OR=0.3, 95% CI;0.12 – 0.8 , P≤ 0.05) with respect to those of the CC wild type. The TT genotype significantly raised the risk of breast cancer women by (OR = 0.2, 95% CI; 0.04 – 0.9, P≤ 0.05).
Conclusion: In women with breast cancer, MMP-2 expression is highly association were observed with positive lymph node, histological classification of breast cancer (ll) higher than other classes, and advanced clinical process (ll).
2. Beeghly-fadiel A, Lu W, Long J, Shu X, Zheng Y, Cai Q, et al. Matrix Metalloproteinase-2 Polymorphisms and Breast Cancer Susceptibility. 2009;18(June):1770–7.
3. Wolff AC, Hammond ME, Schwartz JN, et al American Society of Clinical Oncology/College of American Pathologists: American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med 131:18-43, 2007.
4. Tamimi RM, Byrne C, Colditz GA, Hankinson SE (2007) Endogenous hormone levels, mammographic density, and subsequent risk of breast cancer in postmenopausal women. J Natl Cancer Inst 99: 1178-1187
5. Talvensaari-Mattila A, Paakko P, Blanco-Sequeiros G, Turpeenniemi-Hujanen T. Matrix mettaloproteinase-2 (MMP-2) is associated with the risk for a relapse in postmenopausal patients with node-positive breast carcinoma treated with antiestrogen therapy. Breast Cancer Res Treat 2001;65:55–6
6. Singh, M. and Agrawal, A., 2020. Assessment of Risk Factors of Breast Cancer among Women Attending Tertiary Care Hospital of Chattisgarh: a Case Control Study. Indian Journal of Surgery, pp.1-5.
7. Bray F, Ferlay J, Soerjomataram I. Global Cancer Statistics 2018 : Globocan Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. 2018;394–424.
8. Shah, R., Rosso, K. and Nathanson, S.D., 2014. Pathogenesis, prevention, diagnosis and treatment of breast cancer. World journal of clinical oncology, 5(3), p.28.
9. Mandal BA. Breast Cancer Pathophysiology. Breast Cancer Pathophysiol. 2019;1–3.
10. Das K, Prasad R, Ahmed S, Roy A, Mukherjee A. Biomedicine & Pharmacotherapy Matrix metalloproteinase-2 : A key regulator in coagulation proteases mediated human breast cancer progression through autocrine signaling. Biomed Pharmacother [Internet]. 2018;105(May):395–406.
11. Radisky, E.S. and Radisky, D.C., 2015. Matrix metalloproteinases as breast cancer drivers and therapeutic targets. Frontiers in bioscience (Landmark edition), 20, p.1144.
12. Saarto T, Vehmanen L, Blomqvist C, Elomaa I. A High Serum Matrix Metalloproteinase-2 Level Is Associated with an Adverse Prognosis in Node-Positive Breast Carcinoma. 2004;10:1057–63.
13. Zgajnar, J. (2018) ‘Clinical Presentation , Diagnosis and Staging of Breast Cancer’, pp. 159–176.
14. Habel, A. F. et al. (2019) ‘Common matrix metalloproteinase-2 gene variants and altered susceptibility to breast cancer and associated features in Tunisian women’, (April), pp. 1–8.
15. Chen, Y. et al. (2015) ‘The Impact of Matrix Metalloproteinase 2 on Prognosis and Clinicopathology of Breast Cancer Patients : A Systematic Meta-Analysis’, pp. 1–16.
16. Ranogajec, I., 2017. Matrix Metalloproteinases in Breast Carcinoma. In Proteases in Human Diseases (pp. 3-20). Springer, Singapore.
17. Iliyasu, Y. and Atanda, A.T., 2019. Molecular subtyping of carcinoma of the female breast in a tertiary teaching hospital in Northern Nigeria. Annals of Tropical Pathology, 10(1), p.20.
18. Kleibl, Z. and Kristensen, V. N. (2016) ‘Women at high risk of breast cancer : Molecular characteristics , clinical presentation and management’, The Breast. Elsevier Ltd, 28, pp. 136–144.
19. Beeghly-Fadiel, A., Lu, W., Long, J.R., Shu, X.O., Zheng, Y., Cai, Q., Gao, Y.T. and Zheng, W., 2009. Matrix metalloproteinase-2 polymorphisms and breast cancer susceptibility. Cancer Epidemiology and Prevention Biomarkers, 18(6) : 1770-1776.
20. Habel, A.F., Ghali, R.M., Bouaziz, H., Daldoul, A., Hadj-Ahmed, M., Mokrani, A., Zaied, S., Hechiche, M., Rahal, K., Yacoubi-Loueslati, B. and Almawi, W.Y., 2019. Common matrix metalloproteinase-2 gene variants and altered susceptibility to breast cancer and associated features in Tunisian women. Tumor Biology, 41(4), p.1010428319845749.
21. Zhou, Y., Yu, C., Miao, X., Tan, W., Liang, G., Xiong, P., Sun, T. and Lin, D., 2004. Substantial reduction in risk of breast cancer associated with genetic polymorphisms in the promoters of the matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 genes. Carcinogenesis, 25(3) : 399-404.
22. Néjima, D.B., Zarkouna, Y.B., Gammoudi, A., Manai, M., & Boussen, H. (2014). Prognostic impact of polymorphism of matrix metalloproteinase-2 and metalloproteinase tissue inhibitor-2 promoters in breast cancer in Tunisia: case-control study. Tumor Biology, 36 : 3815-3822.
23. Kawal P, Chandra A, Dhole TN, et al. Correlations of polymorphisms in matrix metalloproteinase-1, -2, and -7 promoters to susceptibility to malignant gliomas. Asian J Neurosurg 2016; 11(2): 160–166.
24. Lei H, Hemminki K, Altieri A, et al. Promoter poly- morphisms in matrix metalloproteinases and their inhibi- tors: few associations with breast cancer susceptibility and progression. Breast Cancer Res Treat 2007; 103(1): 61–69.
25. Roehe AV, Frazzon AP, Agnes G, et al. Detection of polymorphisms in the promoters of matrix metalloprotei- nases 2 and 9 genes in breast cancer in South Brazil: pre- liminary results. Breast Cancer Res Treat 2007; 102(1): 123–124.
26. Maas, P. et al. (2016) ‘Breast Cancer Risk From Modifiable and Nonmodifiable Risk Factors Among White Women in the United States’, 21205(10) : 1295–1302.
27. Zhou, Y. et al. (2004) ‘Substantial reduction in risk of breast cancer associated with genetic polymorphisms in the promoters of the matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 genes’, 25(3) : 399–404.
28. Nouri, M. M. (2019) ‘Breast Cancer Molecular Subtypes in Relation to Age , Stage and Grade among Sudanese Women Patients in Khartoum Oncology Hospital ( 2013 – 2017 )’, 2(August 2017) : 1–9.
29. DeSantis, C., Ma, J., Bryan, L. and Jemal, A., 2014. Breast cancer statistics, 2013. CA: a cancer journal for clinicians, 64(1), pp.52-62.
30. Talvensaari-Mattila A, Pa¨a¨kko¨ P and Turpeenniemi Hujanen T. Matrix metalloproteinase-2 (MMP-2) is asso- ciated with survival in breast carcinoma. Br J Cancer 2003; 89 : 1270–1275.
31. Bergers,G., Brekken,R., Mcmahon,G., Vu,T.H., Itoh,T., Tamaki,K., Tanzawa,K., Thorp,P., Itohara,S., Werb,Z. and Hanahan,D. (2000) Matrix metalloproteinase-9 triggers the angiogenic switch during carci- nogenesis. Nature Cell Biol., 2 : 737-744. 32. Itoh,T., Tanioka,M., Yoshida,H., Yoshioka,T., Nishimoto,H. and Itohara,S. (1998) Reduced angiogenesis and tumor progression in gelatinase A-deficient mice. Cancer Res., 58 : 1048 -1051
33. Ghilardi,G., Biondi,M.L., Caputo,M., Leviti,S., DeMonti,M Guagnellini,E. and Scorza,R. (2002) A single nucleotide polymorphism in the matrix metalloproteinase-3 promoter enhances breast cancer susceptibility. Clin. Cancer Res., 8 : 3820 -3823.
34. Ye,SDhillon,STurner,S.J., Bateman,A.C., Theaker,J.MPickering,R.M., Day,I. and Howell,W.M. (2001) Invasiveness of cuta- neous malignant melanoma is influenced by matrix metalloproteinase 1 gene polymorphism. Cancer Res., 61 : 1296 -1298.
35. Ghilardi,GBiondi,M.LMangoni,J., Leviti,S., DeMonti,MGuagnellini,E. and Scorza,R. (2001) Matrix metalloproteinase-1 promoter polymorphism 1G/2G is correlated with colorectal cancer invasiveness. Clin. Cancer Res., 7 : 2344 -2346