Volume 11, Issue 1 (Vol.11 No.1 Apr 2022)                   rbmb.net 2022, 11(1): 89-101 | Back to browse issues page


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Omran M M H, Fotouh B E, Shousha W G, Ismail A, Ramadan S S. Gene-Gene Interaction Study Between Genetic Polymorphisms of Folate Metabolism and MTR SNPs on Prognostic Features Impact for Breast Cancer. rbmb.net 2022; 11 (1) :89-101
URL: http://rbmb.net/article-1-718-en.html
Microbial Biotechnology Department, Genetic Engineering Division, National Research Centre, Cairo, Egypt (12622).
Abstract:   (2483 Views)
Background: Breast Cancer (BC), the second leading cause of cancer mortality after lung cancer and varied across the world due to genetic and environmental factors. In this study, we evaluated the interaction between the polymorphisms in genes encoding enzymes of folate metabolism: methylenetetrahydrofolate reductase (MTHFR), methionine synthesis reductase (MTR) with the BC prognostic factors.

Methods: This study was conducted on 160 Egyptian subjects, 60 controls and 100 cases. Sequencing, RFLP analysis in addition to statistical analysis including Chi‐squared test, haplotype analysis was used to evaluate associations with BC risk and its clinicopathological parameters. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression.

Results: Strong significant association with breast cancer risk was observed for the haplotype (T-C-G) of MTHFR C677T/ MTHFR A1289C and MTRA2576G and hormonal receptor expression (ER-/PR- /HER2+), bigger and advanced tumor and metastatic lymph nodes. However, no significant difference was
observed for age.

Conclusions: The combination of SNPs from MTHFR and MTR genes has a more synergistically genetic effect on BC disease progression. These SNPs could be used as tumor aggressiveness markers among Egyptian females with BC and could help in saving money and time.
Full-Text [PDF 302 kb]   (1011 Downloads)    
Type of Article: Original Article | Subject: Molecular Biology
Received: 2021/05/22 | Accepted: 2021/07/25 | Published: 2022/05/26

References
1. Sharif MR & Karimian M. MTR-A2756G and breast cancer risk: a study of Iranian women with a meta-analysis. Bioscience Biotechnololgy Research Communication. 2016;9(4):795-803. [DOI:10.21786/bbrc/9.4/32]
2. Awwad N, Yousef AM, Abuhaliema A, Abdalla I, Yousef M. Relationship between genetic polymorphisms in MTHFR (C677T, A1298C and their Haplotypes) and the incidence of breast cancer among Jordanian females-case-control study. Asian Pac J Cancer Prev. 2015;16(12):5007-11. [DOI:10.7314/APJCP.2015.16.12.5007] [PMID]
3. Bonaventure A, Goujon-Bellec S, Rudant J, Orsi L, Leverger G, Baruchel A, et al. Maternal smoking during pregnancy, genetic polymorphisms of metabolic enzymes, and childhood acute leukemia: the ESCALE study (SFCE). Cancer Causes Control. 2012;23(2):329-45. [DOI:10.1007/s10552-011-9882-9] [PMID]
4. Castiglia P, Sanna V, Azara A, et al. Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms in breast cancer a Sardinian preliminary case-control study. Int J Med Sci. 2019;16(8):1089-1095. [DOI:10.7150/ijms.32162] [PMID] [PMCID]
5. Omran MH, Fotouh BE, Shousha WG, Ismail A, Ibrahim NE, Ramadan SS. Strong Correlation of MTHFR Gene Polymorphisms with Breast Cancer and its Prognostic Clinical Factors among Egyptian Females. Asian Pac J Cancer Prev. 2021;22(2):617-626. [DOI:10.31557/APJCP.2021.22.2.617] [PMID] [PMCID]
6. Carvalho DC, Wanderley AV, Mello Junior FAR, Santos AMRD, Leitão LPC, Souza TP, et al. Association of genes ARID5B, CEBPE and folate pathway with acute lymphoblastic leukemia in a population from the Brazilian Amazon region. Leukemia Research Reports. 2019;27(13):100188. [DOI:10.1016/j.lrr.2019.100188] [PMID] [PMCID]
7. Choi SW, Mason JB. Folate and carcinogenesis: an integrated scheme. J Nutr. 2000;130(2):129-32. [DOI:10.1093/jn/130.2.129] [PMID]
8. Omran MH, Ibrahim NE, Youssef SS, et al. Relation of interleukin-1β gene to treatment response in chronic patients infected with HCV genotype 4. The Journal of Infection in Developing Countries. 2013;7(11):851-8. [DOI:10.3855/jidc.3823] [PMID]
9. Omran MH, Nabil W, Youssef SS, El-Sayed M, El Awady MK. Heterogeneity and new epitopes of hepatitis C virus genotype 4. Hepatitis Monthly. 2013;13(8):e10521. [DOI:10.5812/hepatmon.10521]
10. Solé X, Guinó E, Valls J, Iniesta R, Moreno V. SNPStats: a web tool for the analysis of association studies. Bioinform. 2006;22(15):1928-9. [DOI:10.1093/bioinformatics/btl268] [PMID]
11. Omran MH, Khamis M, Nasr N, Massoud AA, Youssef SS, Bader El Din NG, et al. A Study of CC-Chemokine Receptor 5 (CCR5) Polymorphism on the Outcome of HCV Therapy in Egyptian Patients. Hepat Mon. 2013;19;13(12):e13721. [DOI:10.5812/hepatmon.13721]
12. Yuan H., Fu M, Yang X, Huang K. and Ren X. Single nucleotide polymorphism of MTHFR rs1801133 associated with elevated Hcy levels affects susceptibility to cerebral small vessel disease. PeerJ. 2020;8:e8627. [DOI:10.7717/peerj.8627] [PMID] [PMCID]
13. Ward M, Hughes CF, Strain JJ, Reilly R, Cunningham C, Molloy A, et al. Impact of the common MTHFR 677C→T polymorphism on blood pressure in adulthood and role of riboflavin in modifying the genetic risk of hypertension: evidence from the JINGO project. BMC Med. 2020;18(1):318. [DOI:10.1186/s12916-020-01780-x] [PMID] [PMCID]
14. Donepudi M, Kondapalli K, Amos S, Venkanteshan P. Breast cancer statistics and markers. J Cancer Res Ther. 2014;10(3):506-11.
15. Vijg J, Suh Y. Genome instability and aging. Annu Rev Physiol. 2013;75:645-68. [DOI:10.1146/annurev-physiol-030212-183715] [PMID]
16. Rahimi Z, Bozorgi M, Rahimi Z, Shakiba E, Yari K, et al. MTHFR C677T Polymorphism Is Associated with the Risk of Breast Cancer Among Kurdish Population from Western Iran. Int J Cancer Manag. 2019;12(3):e67895. [DOI:10.5812/ijcm.67895]
17. Hardi H, Melki R, Boughaleb Z, et al. Significant association between ERCC2 and MTHR polymorphisms and breast cancer susceptibility in Moroccan population: genotype and haplotype analysis in a case-control study. BMC Cancer. 2018;18:292. [DOI:10.1186/s12885-018-4214-z] [PMID] [PMCID]
18. Chita DS, Tudor A, Christodorescu R, Buleu FN, Sosdean R, Deme SM, et al. MTHFR gene polymorphisms prevalence and cardiovascular risk factors involved in cardioembolic stroke type and severity. Brain Sci. 2020;10(8):476. [DOI:10.3390/brainsci10080476] [PMID] [PMCID]
19. Kumar A, Sharma R, Misra S, Nath M, Kumar P. Relationship between methylenetetrahydrofolate reductase (MTHFR) gene (A1298C) polymorphism with the risk of stroke: A systematic review and meta-analysis. Neurol Res. 2020;42(11):913-922.‏ [DOI:10.1080/01616412.2020.1798107] [PMID]
20. Karimian M, Rezazadeh N, Khamehchian T. Association analysis of methylenetetrahydrofolate reductase common gene polymorphisms with breast cancer risk in an Iranian population: A Case-Control Study and a Stratified Analysis. Asian Pac J Cancer Prev. 2020;21(9):2709-2714. [DOI:10.31557/APJCP.2020.21.9.2709] [PMID] [PMCID]
21. Pepe C, Guidugli L, Sensi E, Aretini P, D'Andrea E, Montagna M. Methyl group metabolism gene polymorphisms as modifier of breast cancer risk in Italian BRCA1/2 carriers. Breast Cancer Res Treat. 2007;103(1):29-36. [DOI:10.1007/s10549-006-9349-y] [PMID]
22. Carvalho Barbosa R, da Costa DM, Cordeiro DE, Vieira AP, Rabenhorst SH. Interaction of MTHFR C677T and A1298C, and MTR A2756G gene polymorphisms in breast cancer risk in a population in Northeast Brazil. Anticancer Res. 2012;32(11):4805-11.
23. Niu Z, Zhao H, Hou X. Association of MTHFR, MTRR and MTR polymorphisms with breast cancer risk: A study in Chinese females. International Journal of Clinical and Experimental Pathology. 2017;10(6):7059-7066.
24. Zhao Y, Chen Z, Ma Y, Xia Q, Zhang F, Fu D, et al. Lack of association between methionine synthase A2756G polymorphism and digestive system cancer risk: Evidence from 39327 subjects. PLoS ONE. 2013;8(4):e61511. [DOI:10.1371/journal.pone.0061511] [PMID] [PMCID]
25. Mo LM, Yang HP, Yang XW, Ruan LH. Methionine synthase A2756G polymorphism influences pediatric acute lymphoblastic leukemia risk: a meta-analysis. Biosci Rep. 2019;39(1):BSR20181770.‏ [DOI:10.1042/BSR20181770] [PMID] [PMCID]
26. Le Marchand L, Donlon T, Hankin JH, Kolonel LN, Wilkens LR, Seifried A. B-vitamin intake, metabolic genes, and colorectal cancer risk (United States). Cancer Causes Control. 2002;13(3):239-48.‏ [DOI:10.1023/A:1015057614870] [PMID]
27. Gong Z, Yao S, Zirpoli G, David Cheng TY, et al. Genetic variants in one-carbon metabolism genes and breast cancer risk in European American and African American women. Int J Cancer. 2015;137(3):666-677. [DOI:10.1002/ijc.29434] [PMID] [PMCID]
28. Lajin B, Alhaj Sakur A, GhabreauL, Alachkar A. Association of polymorphisms in one-carbon metabolizing genes with breast cancer risk in Syrian women. Tumour Biol. 2012;33(4):1133-9. [DOI:10.1007/s13277-012-0354-y] [PMID]
29. Floris M, Sanna D, Castiglia P, Putzu C, Sanna V, Pazzola A, et al. MTHFR, XRCC1 and OGG1 genetic polymorphisms in breast cancer. a case-control study in a population from North Sardinia. BMC Cancer. 2020;20(1):234. [DOI:10.1186/s12885-020-06749-w] [PMID] [PMCID]
30. Piskac-Collier AL, Monroy C, Lopez MS, Cortes A, Etzel CJ, Greisinger AJ, et al. Variants in folate pathway genes as modulators of genetic instability and lung cancer risk. Genes Chromosomes Cancer. 2011;50(1):1-12. [DOI:10.1002/gcc.20826] [PMID]
31. Poodineh M, Saravani R, Mirhosseini M, Sargazi S. Association of two methylenetetrahydrofolate reductase polymorphisms (rs1801133, rs1801131) with the risk of type 2 diabetes in South-East of Iran. Rep Biochem Mol Biol. 2019;8(2):178-183.
32. Arpino G, Milano M, De Placido S. Features of aggressive breast cancer. Breast. 2015;24(5):594-600. [DOI:10.1016/j.breast.2015.06.001] [PMID]
33. Waseem M, Hussain SR, Kumar S, et al. Association of MTHFR (C677T) gene polymorphism with breast cancer in North India. Biomark Cancer. 2016;8:111-117. [DOI:10.4137/BIC.S40446] [PMID] [PMCID]
34. Nourolahzadeh Z, Houshmand S M, Mostafa Mohammad F, Ghorbian S. Correlation between Lsp1 (Rs3817198) and Casc (Rs4784227) Polymorphisms and the Susceptibility to Breast Cancer. Reports of biochemistry & molecular biology. 2020;9(3):291-296. [DOI:10.29252/rbmb.9.3.291] [PMID] [PMCID]

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