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Current Drug Metabolism


ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

Research Article

Meta-analysis of NFKB1-94 ATTG Ins/Del Polymorphism and Risk of Breast Cancer

Author(s): Jyothsna Kancharla, I. Devi Vara Prasad, Lakkakula V.K.S. Bhaskar*, Pallaval Veera Bramhachari* and Afroz Alam*

Volume 21 , Issue 3 , 2020

Page: [221 - 225] Pages: 5

DOI: 10.2174/1389200221666200310113118

Price: $65


Background: Breast cancer (BC) accounts for one of the most prevalent malignancies in the world. Inflammatory molecules modulate tumor microenvironment in BC that promotes tumor growth and metastasis. NF-κB (a transcription factor) that regulates multiple immune functions and acts as a crucial mediator of inflammatory responses.

Objective: The present study is aimed to quantitatively summarize the relation of NFKB1-94 ATTG (I, insertion/D, deletion) variant and risk of BC.

Methods: Further, the meta-analysis includes three independent case-control investigations that focus on NFKB1-94, ATTG I/D polymorphism, and BC patients. Web of Science, PubMed and Embase databases were used to retrieve relevant data. OR and 95% confidence interval of pooled studies were analyzed by using the MetaGenyo web tool.

Results: This study revealed a high heterogeneity. In all three genetic comparison models, the NFKB1-94 ATTG I/D variant is not related to the risk of BC. Further, no publication bias on the connection between NFKB1-94 ATTG I/D variant and risk of BC was observed.

Conclusion: To summarize, our meta-analysis demonstrates that the NFKB1-94 ATTG I/D polymorphism is not a major risk factor for BC.

Keywords: Breast cancer, inflammation, NFKB1-94, ATTG I/D polymorphism, meta-analysis, transcription factor.

Graphical Abstract
Huang, A.; Cao, S.; Tang, L. The tumor microenvironment and inflammatory breast cancer. J. Cancer, 2017, 8(10), 1884-1891.
[] [PMID: 28819386]
Sawe, R.T.; Mining, S.K.; Ofulla, A.V.; Patel, K.; Guyah, B.; Chumba, D.; Prosperi, J.R.; Kerper, M.; Shi, Z.; Sandoval-Cooper, M.; Taylor, K.; Badve, S.; Stack, M.S.; Littlepage, L.E. Tumor infiltrating leukocyte density is independent of tumor grade and molecular subtype in aggressive breast cancer of Western Kenya. Trop. Med. Health, 2017, 45, 19.
[] [PMID: 28794686]
Morgillo, F.; Dallio, M.; Della Corte, C.M.; Gravina, A.G.; Viscardi, G.; Loguercio, C.; Ciardiello, F.; Federico, A. Carcinogenesis as a result of multiple inflammatory and oxidative hits: a comprehensive review from tumor microenvironment to gut microbiota. Neoplasia, 2018, 20(7), 721-733.
[] [PMID: 29859426]
Liu, T.; Zhang, L.; Joo, D.; Sun, S-C. NF-κB signaling in inflammation. Signal Transduct. Target. Ther., 2017, 2, 17023.
[] [PMID: 29158945]
Nakshatri, H.; Bhat-Nakshatri, P.; Martin, D.A.; Goulet, R.J., Jr; Sledge, G.W., Jr Constitutive activation of NF-kappaB during progression of breast cancer to hormone-independent growth. Mol. Cell. Biol., 1997, 17(7), 3629-3639.
[] [PMID: 9199297]
Sankardas, P.A.; Lavu, V.; Lakakula, B.V.K.S.; Rao, S.R. Differential expression of periostin, sclerostin, receptor activator of nuclear factor-κB, and receptor activator of nuclear factor-κB ligand genes in severe chronic periodontitis. J. Investig. Clin. Dent., 2019, 10(1)e12369
[] [PMID: 30375186]
Mulero, M.C.; Wang, V.Y-F.; Huxford, T.; Ghosh, G. Genome reading by the NF-κB transcription factors. Nucleic Acids Res., 2019, 47(19), 9967-9989.
[] [PMID: 31501881]
Karban, A.S.; Okazaki, T.; Panhuysen, C.I.; Gallegos, T.; Potter, J.J.; Bailey-Wilson, J.E.; Silverberg, M.S.; Duerr, R.H.; Cho, J.H.; Gregersen, P.K.; Wu, Y.; Achkar, J.P.; Dassopoulos, T.; Mezey, E.; Bayless, T.M.; Nouvet, F.J.; Brant, S.R. Functional annotation of a novel NFKB1 promoter polymorphism that increases risk for ulcerative colitis. Hum. Mol. Genet., 2004, 13(1), 35-45.
[] [PMID: 14613970]
Chen, L.P.; Cai, P.S.; Liang, H.B. Association of the genetic polymorphisms of NFKB1 with susceptibility to ovarian cancer. Genet. Mol. Res., 2015, 14(3), 8273-8282.
[] [PMID: 26345753]
Chen, Y.; Lu, R.; Zheng, H.; Xiao, R.; Feng, J.; Wang, H.; Gao, X.; Guo, L. The NFKB1 polymorphism (rs4648068) is associated with the cell proliferation and motility in gastric cancer. BMC Gastroenterol., 2015, 15, 21.
[] [PMID: 25888547]
Cui, X.; Yan, H.; Ou, T.W.; Jia, C.S.; Wang, Q.; Xu, J.J. Genetic variations in inflammatory response genes and their association with the risk of prostate cancer. BioMed Res. Int., 2015, 2015674039
[] [PMID: 26788504]
Eskandari-Nasab, E.; Hashemi, M.; Ebrahimi, M.; Amininia, S. The functional 4-bp insertion/deletion ATTG polymorphism in the promoter region of NF-KB1 reduces the risk of BC. Cancer Biomark., 2016, 16(1), 109-115.
[] [PMID: 26835711]
Gupta, A.; Agnihotri, V.; Kumar, R.; Upadhyay, A.D.; Bhaskar, S.; Dwivedi, S.; Dey, S. Effects of tobacco habits on the polymorphism of NFKB1 and NFKB1A gene of head and neck squamous cell carcinoma in indian population. Asian Pac. J. Cancer Prev., 2017, 18(7), 1855-1859.
[PMID: 28749120]
Wang, X.; Peng, H.; Liang, Y.; Sun, R.; Wei, T.; Li, Z.; Gong, Y.; Gong, R.; Liu, F.; Zhang, L.; Zhu, J. A functional insertion/deletion polymorphism in the promoter region of the NFKB1 gene increases the risk of papillary thyroid carcinoma. Genet. Test. Mol. Biomarkers, 2015, 19(3), 167-171.
[] [PMID: 25692306]
Wang, Y.; Chen, L.; Pan, L.; Xue, J.; Yu, H. The association between NFKB1-94ins/del ATTG polymorphism and non-small cell lung cancer risk in a Chinese Han population. Int. J. Clin. Exp. Med., 2015, 8(5), 8153-8157.
[PMID: 26221384]
Wang, Z.; Liu, Q-L.; Sun, W.; Yang, C-J.; Tang, L.; Zhang, X.; Zhong, X-M. Genetic polymorphisms in inflammatory response genes and their associations with breast cancer risk. Croat. Med. J., 2014, 55(6), 638-646.
[] [PMID: 25559835]
Sapcharoen, K.; Sanguansermsri, P.; Yasothornsrikul, S.; Muisuk, K.; Srikummool, M. Gene combination of CD44 rs187116, CD133 rs2240688, NF-κB1 rs28362491 and GSTM1 deletion as a potential biomarker in risk prediction of breast cancer in lower Northern Thailand. Asian Pac. J. Cancer Prev., 2019, 20(8), 2493-2502.
[] [PMID: 31450925]
Xia, Y.; Shen, S.; Verma, I.M. NF-κB, an active player in human cancers. Cancer Immunol. Res., 2014, 2(9), 823-830.
[] [PMID: 25187272]
Barham, W.; Chen, L.; Tikhomirov, O.; Onishko, H.; Gleaves, L.; Stricker, T.P.; Blackwell, T.S.; Yull, F.E. Aberrant activation of NF-κB signaling in mammary epithelium leads to abnormal growth and ductal carcinoma in situ. BMC Cancer, 2015, 15, 647-647.
[] [PMID: 26424146]
Wang, W.; Nag, S.A.; Zhang, R. Targeting the NFκB signaling pathways for breast cancer prevention and therapy. Curr. Med. Chem., 2015, 22(2), 264-289.
[] [PMID: 25386819]
Kim, J-Y.; Jung, H.H.; Ahn, S.; Bae, S.; Lee, S.K.; Kim, S.W.; Lee, J.E.; Nam, S.J.; Ahn, J.S.; Im, Y.H.; Park, Y.H. The relationship between nuclear factor (NF)-κB family gene expression and prognosis in triple-negative breast cancer (TNBC) patients receiving adjuvant doxorubicin treatment. Sci. Rep., 2016, 6, 31804.
[] [PMID: 27545642]
Khongthong, P.; Roseweir, A. K.; Edwards, J. The NF-KB pathway and endocrine therapy resistance in breast cancer. 2019, 26 R369
Sarkar, D.K.; Jana, D.; Patil, P.S.; Chaudhari, K.S.; Chattopadhyay, B.K.; Chikkala, B.R.; Mandal, S.; Chowdhary, P. Role of NF-κB as a prognostic marker in breast cancer: a pilot study in Indian patients. Indian J. Surg. Oncol., 2013, 4(3), 242-247.
[] [PMID: 24426730]
Pires, B.R.B.; Mencalha, A.L.; Ferreira, G.M.; de Souza, W.F.; Morgado-Díaz, J.A.; Maia, A.M.; Corrêa, S.; Abdelhay, E.S.F.W. NF-kappaB is involved in the regulation of emt genes in breast cancer cells. PLoS One, 2017, 12(1)e0169622
[] [PMID: 28107418]
Murray, J.L.; Thompson, P.; Yoo, S.Y.; Do, K.A.; Pande, M.; Zhou, R.; Liu, Y.; Sahin, A.A.; Bondy, M.L.; Brewster, A.M. Prognostic value of single nucleotide polymorphisms of candidate genes associated with inflammation in early stage breast cancer. Breast Cancer Res. Treat., 2013, 138(3), 917-924.
[] [PMID: 23529385]
Curran, J.E.; Weinstein, S.R.; Griffiths, L.R. Polymorphic variants of NFKB1 and its inhibitory protein NFKBIA, and their involvement in sporadic breast cancer. Cancer Lett., 2002, 188(1-2), 103-107.
[] [PMID: 12406554]

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