Research article Special Issues

Effect of Rs5746136 genotypes on SOD activity and biomarkers levels in breast cancer patients

  • Received: 08 September 2022 Revised: 16 November 2022 Accepted: 24 November 2022 Published: 07 December 2022
  • Oxidative stress factors are among the most common carcinogens, Superoxide dismutase enzyme-2 (SOD2) is an endogenous antioxidant involved in the scavenging of superoxide anions. This study aimed to investigate the effect of the SOD2 gene polymorphism (rs5746136) on SOD activity and biomarker levels in breast cancer patients. This study aimed to investigate the effect of SOD2 gene (rs5746136) polymorphisms on SOD activity and biomarkers levels in breast cancer patients. The spectrophotometry methods were used to detect malondialdehyde (MDA) and Catalase (CAT), Superoxide dismutase (SOD), and Glutathione (GSH) levels, which reflect antioxidant capacity, and the genotypes of rs5746136 were detected utilize PCR and RFLP. According to the current findings, the GA genotype of the control group was the most common (70%), followed by GG and AA genotypes (26.7% and 3.3%) respectively. In the patient group, the most common genotype was GG (45.6%), followed by the GA genotype (42.8%) and then the AA genotype (11.4%) The frequency of heterozygous genotype G/A compared to the homozygous genotype (G/G) [OR = 0.3571, 95% CI = 0.1375–0.9277, P = 0.0345]. The AA genotype is significantly associated with an increased risk of developing BC [OR = 2.00, p = 0.5403, CI: 0.2175–18.3883]. No significant differences were found in frequencies of the A allele between patients and control groups [OR = 0.7872, 95% CI = 0.4198–1.4762, P = 0.4558]. In addition, there are modest (P 0.05) relationships between serum biochemical parameters levels and rs5746136 genotype in breast cancer patients, but a substantial association between serum SOD activity and GSH concentration and GA and GG rs5746136 genotype in the control group. In conclusion, the current investigation suggests that the AA genotype of (rs5746136) in the MnSOD gene may be associated with an increased risk of breast cancer. The chosen SOD2 variants (rs5746136) play a crucial role in controlling the activity of the SOD enzyme.

    Citation: Hadi Sajid Abdulabbas, Yasir Haider Al-Mawlah. Effect of Rs5746136 genotypes on SOD activity and biomarkers levels in breast cancer patients[J]. AIMS Biophysics, 2023, 10(1): 1-11. doi: 10.3934/biophy.2023001

    Related Papers:

  • Oxidative stress factors are among the most common carcinogens, Superoxide dismutase enzyme-2 (SOD2) is an endogenous antioxidant involved in the scavenging of superoxide anions. This study aimed to investigate the effect of the SOD2 gene polymorphism (rs5746136) on SOD activity and biomarker levels in breast cancer patients. This study aimed to investigate the effect of SOD2 gene (rs5746136) polymorphisms on SOD activity and biomarkers levels in breast cancer patients. The spectrophotometry methods were used to detect malondialdehyde (MDA) and Catalase (CAT), Superoxide dismutase (SOD), and Glutathione (GSH) levels, which reflect antioxidant capacity, and the genotypes of rs5746136 were detected utilize PCR and RFLP. According to the current findings, the GA genotype of the control group was the most common (70%), followed by GG and AA genotypes (26.7% and 3.3%) respectively. In the patient group, the most common genotype was GG (45.6%), followed by the GA genotype (42.8%) and then the AA genotype (11.4%) The frequency of heterozygous genotype G/A compared to the homozygous genotype (G/G) [OR = 0.3571, 95% CI = 0.1375–0.9277, P = 0.0345]. The AA genotype is significantly associated with an increased risk of developing BC [OR = 2.00, p = 0.5403, CI: 0.2175–18.3883]. No significant differences were found in frequencies of the A allele between patients and control groups [OR = 0.7872, 95% CI = 0.4198–1.4762, P = 0.4558]. In addition, there are modest (P 0.05) relationships between serum biochemical parameters levels and rs5746136 genotype in breast cancer patients, but a substantial association between serum SOD activity and GSH concentration and GA and GG rs5746136 genotype in the control group. In conclusion, the current investigation suggests that the AA genotype of (rs5746136) in the MnSOD gene may be associated with an increased risk of breast cancer. The chosen SOD2 variants (rs5746136) play a crucial role in controlling the activity of the SOD enzyme.



    加载中


    Conflict of interest



    The authors declare no conflict of interest.

    [1] Glynn SA, Boersma BJ, Howe TM, et al. (2009) A mitochondrial target sequence polymorphism in manganese superoxide dismutase predicts inferior survival in breast cancer patients treated with cyclophosphamide. Clin Cancer Res 15: 4165-4173. https://doi.org/10.1158/1078-0432.CCR-09-0119
    [2] Barretina J, Caponigro G, Stransky N, et al. (2012) The cancer cell line encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature 483: 603-607. https://doi.org/10.1038/nature11003
    [3] Soerensen M, Christensen K, Stevnsner T, et al. (2009) The Mn-superoxide dismutase single nucleotide polymorphism rs4880 and the glutathione peroxidase 1 single nucleotide polymorphism rs1050450 are associated with aging and longevity in the oldest old. Mech Ageing Dev 130: 308-314. https://doi.org/10.1016/j.mad.2009.01.005
    [4] Yari A, Saleh-Gohari N, Mirzaee M, et al. (2022) A study of associations between rs9349379 (PHACTR1), rs2891168 (CDKN2B-AS), rs11838776 (COL4A2) and rs4880 (SOD2) polymorphic variants and coronary artery disease in Iranian population. Biochem Genet 60: 106-126. https://doi.org/10.1007/s10528-021-10089-0
    [5] Ascencio-Montiel IDJ, Parra EJ, Valladares-Salgado A, et al. (2013) SOD2 gene Val16Ala polymorphism is associated with macroalbuminuria in Mexican Type 2 Diabetes patients: a comparative study and meta-analysis. BMC Med Genet 14: 110. https://doi.org/10.1186/1471-2350-14-110
    [6] Huober J, Schneeweiss A, Hartkopf AD, et al. (2020) Update breast cancer 2020 Part 3—early breast cancer. Obstet Gynecol 80: 1105-1114. https://doi.org/10.1055/a-1270-7208
    [7] Alateyah N, Gupta I, Rusyniak RS, et al. (2022) SOD2, a potential transcriptional target underpinning CD44-promoted breast cancer progression. Molecules 27: 811. https://doi.org/10.3390/molecules27030811
    [8] Frederiks WM, Bosch KS, Hoeben KA, et al. (2010) Renal cell carcinoma and oxidative stress: the lack of peroxisomes. Acta Histochem 112: 364-371. https://doi.org/10.1016/j.acthis.2009.03.003
    [9] Gallegos-Arreola MP, Ramírez-Hernández MA, Figuera LE, et al. (2020) The rs2234694 and 50 bp insertion/deletion polymorphisms of the SOD1 gene are associated with breast cancer risk in a Mexican population. Eur Rev Med Pharmaco 24: 8017-8027.
    [10] Romero-Cordoba SL, Salido-Guadarrama I, Rebollar-Vega R, et al. (2021) Comprehensive omic characterization of breast cancer in Mexican-Hispanic women. Nat Commun 12: 2245. https://doi.org/10.1038/s41467-021-22478-5
    [11] Lemus-Varela ML, García-Valdez LM, Ramírez-Patiño R, et al. (2021) Association of the SOD2 Rs5746136 C > T polymorphisms with the risk of persistent pulmonary hypertension of the newborn. J Pediatr Neonatal 3: 1-5.
    [12] Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47: 469-474. https://doi.org/10.1111/j.1432-1033.1974.tb03714.x
    [13] Rendic S, Peter Guengerich F (2012) Summary of information on the effects of ionizing and non-ionizing radiation on cytochrome P450 and other drug metabolizing enzymes and transporters. Curr Drug Metab 13: 787-814. https://doi.org/10.2174/138920012800840356
    [14] Chen Y, Pei J (2011) Possible risk modifications in the association between MnSOD Ala-9Val polymorphism and breast cancer risk: subgroup analysis and evidence-based sample size calculation for a future trial. Breast Cancer Res Tr 125: 495-504. https://doi.org/10.1007/s10549-010-0978-9
    [15] Mitrunen K, Sillanpää P, Kataja V, et al. (2001) Association between manganese superoxide dismutase (MnSOD) gene polymorphism and breast cancer risk. Carcinogenesis 22: 827-829. https://doi.org/10.1093/carcin/22.5.827
    [16] Nawab SN, Zehra S, Fawwad A, et al. (2017) A study on catalase gene promoter polymorphism-21 A/T (rs7943316) in healthy pakistani population. Pak J Med Sci 33: 1521-1524. https://doi.org/10.12669/pjms.336.13188
    [17] Borgstahl GEO, Parge HE, Hickey MJ, et al. (1996) Human mitochondrial manganese superoxide dismutase polymorphic variant Ile58Thr reduces activity by destabilizing the tetrameric interface. Biochemistry-US 35: 4287-4297. https://doi.org/10.1021/bi951892w
    [18] Moron MS, Depierre JW, Mannervik B (1979) Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. BBA-Gen Subjects 582: 67-78. https://doi.org/10.1016/0304-4165(79)90289-7
    [19] Garcia-Moreno C, Heise L, Jansen HAFM, et al. (2005) Violence against women. Science 310: 1282-1283. https://doi.org/10.1126/science.1121400
    [20] Al-Mawlah YH, Naji MZ, Al-Imari MJ, et al. (2022) Micro-RNA evaluation, specification, and stabilization study in mixed/non-mixed body fluids as a specific molecular marker. J Adv Biotechnol Exp Ther 5: 347-357. https://doi.org/10.5455/JABET.2022.D120
    [21] Al-Kashwan TA, Algenabi AHA, Omara AM, et al. (2021) Association of vitamin D receptor gene polymorphisms BsmI (rs 1544410) and TaqI rs (731236) with the type 2 diabetes mellitus in Iraqi patients from the middle Euphrates region. Meta Gene 28: 100854. https://doi.org/10.1016/j.mgene.2021.100854
    [22] Kaftan AN, Hussain MK, Algenabi AHA, et al. (2021) Association of sunshine vitamin receptor gene polymorphisms (rs2228570) and (rs7975232) with the type 2 diabetes mellitus in Iraqi patients from the middle Euphrates region. Gene Rep 22: 100977. https://doi.org/10.1016/j.genrep.2020.100977
    [23] Kocabaş NA, Şardaş S, Cholerton S, et al. (2005) Genetic polymorphism of manganese superoxide dismutase (MnSOD) and breast cancer susceptibility. Cell Biochem Funct 23: 73-76. https://doi.org/10.1002/cbf.1128
    [24] Hashim AM, Al-Harbi SJ, Burhan MM, et al. (2023) Histological and physiological determinants of hypothyroidism in patients and its relationship with lipid profile. J Adv Biotechnol Exp Ther 6: 9-16. https://doi.org/10.5455/jabet.2023.d101
    [25] Jabir FA, Hoidy WH (2018) Pharmacogenetics as personalized medicine: Association investigation of SOD2 rs4880, CYP2C19 rs4244285, and FCGR2A rs1801274 polymorphisms in a breast cancer population in Iraqi women. Clin Breast Cancer 18: e863-e868. https://doi.org/10.1016/j.clbc.2018.01.009
    [26] Kinnula VL, Crapo JD (2004) Superoxide dismutases in malignant cells and human tumors. Free Radical Bio Med 36: 718-744. https://doi.org/10.1016/j.freeradbiomed.2003.12.010
    [27] Tengström M, Mannermaa A, Kosma VM, et al. (2014) MnSOD rs4880 and XPD rs13181 polymorphisms predict the survival of breast cancer patients treated with adjuvant tamoxifen. Acta Oncol 53: 769-775. https://doi.org/10.3109/0284186X.2014.892210
    [28] Kakkoura MG, Demetriou CA, Loizidou MA, et al. (2016) MnSOD and CAT polymorphisms modulate the effect of the Mediterranean diet on breast cancer risk among Greek-Cypriot women. Eur J Nutr 55: 1535-1544. https://doi.org/10.1007/s00394-015-0971-5
    [29] Hecht F, Pessoa CF, Gentile LB, et al. (2016) The role of oxidative stress on breast cancer development and therapy. Tumor Biol 37: 4281-4291. https://doi.org/10.1007/s13277-016-4873-9
    [30] Zhang Y, Zhang C, Guan S, et al. (2017) Association between SOD2 rs6917589, rs2842980, rs5746136 and rs4880 polymorphisms and primary open angle glaucoma in a northern Chinese population. Int J Clin Exp Pathol 10: 3930-3938.
    [31] Cengiz M, Ozaydin A, Ozkilic AC, et al. (2007) The investigation of GSTT1, GSTM1 and SOD polymorphism in bladder cancer patients. Int Urol Nephrol 39: 1043-1048. https://doi.org/10.1007/s11255-007-9179-9
    [32] Liu H, Gu J, Jin Y, et al. (2021) Genetic variants in N6-methyladenosine are associated with bladder cancer risk in the Chinese population. Arch Toxicol 95: 299-309. https://doi.org/10.1007/s00204-020-02911-2
    [33] Saify K, Saadat M (2015) Expression patterns of antioxidant genes in human SH-SY5Y cells after treatment with methadone. Psychiat Res 230: 116-119. https://doi.org/10.1016/j.psychres.2015.08.027
    [34] Al-Mawlah YH, Al-Darraji MN, Al-Imari MJ (2022) Study of small non-coding RNA (miRNA) expression pattern of fertile/infertile male semen. Acta Inform Med 30: 205-212. https://doi.org/10.5455/aim.2022.30.205-212
    [35] Wiener HW, Perry RT, Chen Z, et al. (2007) A polymorphism in SOD2 is associated with development of Alzheimer's disease. Genes Brain Behav 6: 770-776. https://doi.org/10.1111/j.1601-183X.2007.00308.x
    [36] Mahmoudinasab H, Saadat M (2016) Short-term exposure to 50-Hz electromagnetic field and alterations in NQO1 and NQO2 expression in MCF-7 cells. Open Access Maced J Med Sci 4: 548-550. https://doi.org/10.3889/oamjms.2016.102
    [37] Saify K (2016) Genetic polymorphisms in the promoter region of catalase gene, creates new potential PAX-6 and STAT4 response elements. Mol Biol Res Commun 5: 97-100.
    [38] Saify K, Saadat M (2017) Influence of a 50bp Ins/Del polymorphism at promoter of the superoxide dismutase-1 on gene expression and risk of heroin dependency. Environ Health Prev 22: 4. https://doi.org/10.1186/s12199-017-0617-8
    [39] Al-Mawlah YH, Alasadi YF, Al-Darraji MN (2021) Association between genetic polymorphisms of (Cu/ZnSOD and CAT C262T) and the risk of breast cancer. Gene Rep 25: 101401. https://doi.org/10.1016/j.genrep.2021.101401
    [40] Liu Y, Zha L, Li B, et al. (2014) Correlation between superoxide dismutase 1 and 2 polymorphisms and susceptibility to oral squamous cell carcinoma. Exp Ther Med 7: 171-178. https://doi.org/10.3892/etm.2013.1375
    [41] Gitik M, Srivastava V, Hodgkinson CA, et al. (2016) Association of superoxide dismutase 2 (SOD2) genotype with gray matter volume shrinkage in chronic alcohol users: replication and further evaluation of an addiction gene panel. Int J Neuropsychoph 19. https://doi.org/10.1093/ijnp/pyw033
    [42] Boroumand F, Mahmoudinasab H, Saadat M (2018) Association of the SOD2 (rs2758339 and rs5746136) polymorphisms with the risk of heroin dependency and the SOD2 expression levels. Gene 649: 27-31. https://doi.org/10.1016/j.gene.2018.01.074
    [43] Mahmoudinasab H, Sanie-Jahromi F, Saadat M (2016) Effects of extremely low-frequency electromagnetic field on expression levels of some antioxidant genes in human MCF-7 cells. Mol Biol Res Commun 5: 77-85.
  • Reader Comments
  • © 2023 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

Metrics

Article views(1588) PDF downloads(191) Cited by(0)

Article outline

Figures and Tables

Figures(1)  /  Tables(2)

Other Articles By Authors

/

DownLoad:  Full-Size Img  PowerPoint
Return
Return

Catalog