RAD51-UTR haplotype genetic polymorphisms and susceptibility to breast cancer in women from Jordanian population
DOI:
https://doi.org/10.32471/exp-oncology.2312-8852.vol-43-no-2.16338Keywords:
breast cancer, DNA repair pathway, prognosis, RAD51-UTRAbstract
Summary. Background: Genetic predisposition to breast cancer (BC) has been extensively explored to achieve an enhanced understanding of the biology of BC. Targeting candidate genes to screen different genetic variants such as RAD51 gene that plays a critical role in DNA repair pathways including the double-strand break repair system is an important task. Aim: To study several single nucleotide polymorphisms (SNPs) within RAD51-UTR gene and to find their relationship with BC risk and prognosis among Jordanian females. Materials and Methods: In this case-control study, DNA sequencing technique was used to screen SNPs within the untranslated region (UTR) of RAD51 in 206 cases and 185 controls and the resulting data were statistically analyzed using different types of genetic analyses. Patients’ clinical and pathological features were obtained from their medical records to perform genotype-phenotype association analysis. Results: Our findings show a significant association between both SNPs rs528590644, rs1801320 and BC risk (p = 0.016). We estimated the correlation between many of BC prognostic factors and BC risk, and we found an association between rs1801321 and age at first menstruation (p = 0.032) in addition to a strong correlation between age at BC diagnosis and rs1801320 (p = 0.008). Conclusion: RAD51-UTR polymorphisms may be involved in BC development and progression.
References
Ferlay J, Colombet M, Soerjomataram I, et al. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries and 25 major cancers in 2018. Eur J Cancer 2018; 103: 356–87.
Shiovitz S, Korde LA. Genetics of breast cancer: a topic in evolution. Ann Oncol 2015; 26: 1291–9.
Stratton MR, Rahman N. The emerging landscape of breast cancer susceptibility. Nat Genet 2008; 40: 17.
King M-C, Marks JH, Mandell JB. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 2003; 302: 643–6.
Cuzick J, Brentnall A, Dowsett M. Dowsett. SNPs for breast cancer risk assessment. Oncotarget 2017; 8: 99211.
Easton DF, Pharoah PD, Antoniou AC, et al. Gene-panel sequencing and the prediction of breast-cancer risk. N Engl J Med 2015; 372: 2243–57.
Vamvakas S, Vock EH, Lutz WK. On the role of DNA double-strand breaks in toxicity and carcinogenesis. Crit Rev Toxicol 1997; 27: 155–74.
Haber JE. Partners and pathways: repairing a double-strand break. Trends Genet 2000; 16: 259–64.
Gullotta F, De Marinis E, Ascenzi P, et al. Targeting the DNA double strand breaks repair for cancer therapy. Curr Med Chem 2010; 17: 2017–48.
Scott RJ. DNA double strand break repair and its association with inherited predispositions to breast cancer. Hered Cancer Clin Pract 2004; 2: 37.
Tavtigian SV, Oefner PJ, Babikyan D, et al. Rare, evolutionarily unlikely missense substitutions in ATM confer increased risk of breast cancer. Am J Hum Genet 2009; 85: 427–46.
Seal S, Thompson D, Renwick A, et al. Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles. Nat Genet 2006; 38: 1239–41.
Le Calvez-Kelm F, Lesueur F, Damiola F, et al. Rare, evolutionarily unlikely missense substitutions in CHEK2 contribute to breast cancer susceptibility: results from a breast cancer family registry case-control mutation-screening study. Breast Cancer Res 2011; 13: R6.
Lambert S, Lopez BS. Characterization of mammalian RAD51 double strand break repair using non‐lethal dominant‐negative forms. EMBO J 2000; 19: 3090–9.
Baumann P, West SC. Role of the human RAD51 protein in homologous recombination and double-stranded-break repair. Trends Biochem Sci 1998; 23: 247–51.
Kim PM, Allen C, Wagener BM, et al. Overexpression of human RAD51 and RAD52 reduces double-strand break-induced homologous recombination in mammalian cells. Nucleic Acids Res 2001; 29: 4352–60.
Lose F, Lovelock P, Chenevix-Trench G, et al. Variation in the RAD51 gene and familial breast cancer. Breast Cancer Res 2006; 8: R26.
Hiramoto T, Nakanishi T, Sumiyoshi T, et al. Mutations of a novel human RAD54 homologue, RAD54B, in primary cancer. Oncogene 1999; 18: 3422–6.
Korak T, Ergul E, Uren N, et al. RAD51 (rs1801320) gene polymorphism and breast cancer risk in Turkish population. Int J Clin Exp Pathol 2017; 10: 2181–6.
Krivokuca AM, Malisic EJ, Dobricic JD, et al. RAD51 135G> C and TP53 Arg72Pro polymorphisms and susceptibility to breast cancer in Serbian women. Fam Cancer 2014; 13: 173–80.
Kato M, Yano K-i, Matsuo F, et al. Identification of RAD51 alteration in patients with bilateral breast cancer. J Hum Genet 2000; 45: 133–7.
Rapakko K, Heikkinen K, Karppinen S-M, et al. Screening for RAD51 and BRCA2 BRC repeat mutations in breast and ovarian cancer families. Cancer Lett 2006; 236: 142–7.
Smolarz B, Michalska MM, Samulak D, et al. Polymorphism of DNA repair genes in breast cancer. Oncotarget 2019; 10: 527.
Grešner P, Jabłońska E, Gromadzińska J. RAD51 paralogs and the risk of unselected breast cancer: A case-control study. PloS One 2020; 15: e0226976.
Parvin S, Islam MS, Al-Mamun MMA, et al. Association of BRCA1, BRCA2, RAD51, and HER2 gene polymorphisms with the breast cancer risk in the Bangladeshi population. Breast Cancer 2017; 24: 229–37.
Le Calvez-Kelm F, Oliver J, Damiola F, et al. RAD51 and breast cancer susceptibility: no evidence for rare variant association in the Breast Cancer Family Registry study. PLoS One 2012; 7: e52374.
Al-Zoubi MS, Mazzanti CM, Zavaglia K, et al. Homozygous T172T and Heterozygous G135C variants of homologous recombination repairing protein RAD51 are related to sporadic breast cancer susceptibility. Biochem Genet 2016; 54: 83–94.
Bae JS, Pasaje CFA, Park B-L, et al. Genetic association analysis of ERBB4 polymorphisms with the risk of schizophrenia and SPEM abnormality in a Korean population. Brain Res 2012; 1466: 146–51.
Nikolaev A, Yang ES. The impact of DNA repair pathways in cancer biology and therapy. Cancers 2017; 19: 126.
Taylor EM, Lehmann AR. Conservation of eukaryotic DNA repair mechanisms. Int J Radiat Biol 1998; 74: 277–86.
Meek DW. Tumour suppression by p53: a role for the DNA damage response? Nat Rev Cancer 2009; 9: 714–23.
Bhattacharya S, Srinivasan K, Abdisalaam S, et al. RAD51 interconnects between DNA replication, DNA repair and immunity. Nucleic Acids Res 2017; 45: 4590–605.
Benson FE, Baumann P, West SC. Synergistic actions of RAD51 and Rad52 in recombination and DNA repair. Nature 1998; 391: 401–4.
Tambini CE, Spink KG, Ross CJ, et al. The importance of XRCC2 in RAD51-related DNA damage repair. DNA repair 2010; 9: 517–25.
Lord CJ, Ashworth A. RAD51, BRCA2 and DNA repair: a partial resolution. Nat Struct Mol Biol 2007; 14: 461–2.
Blasiak J, Przybyłowska K, Czechowska A, et al. Analysis of the G/C polymorphism in the 5′-untranslated region of the RAD51 gene in breast cancer. Acta Biochim Pol 2003; 50: 249–53.
Krupa R, Synowiec E, Pawlowska E, et al. Polymorphism of the homologous recombination repair genes RAD51 and XRCC3 in breast cancer. Exp Mol Pathol 2009; 87: 32–5.
Gao L-B, Pan X-M, Li L-J, et al. RAD51 135G/C polymorphism and breast cancer risk: a meta-analysis from 21 studies. Breast Cancer Res 2011; 125: 827–35.
Sekhar D, Pooja S, Kumar S, et al. RAD51 135G> C substitution increases breast cancer risk in an ethnic-specific manner: a meta-analysis on 21236 cases and 19407 controls. Sci Rep 2015; 5: 1–10.
Sliwinski T, Krupa R, Majsterek I, et al. Polymorphisms of the BRCA2 and RAD51 genes in breast cancer. Breast Cancer Res Treat 2005; 94: 105–9.
Synowiec E, Stefanska J, Morawiec Z, et al. Association between DNA damage, DNA repair genes variability and clinical characteristics in breast cancer patients. Mutat Res 2008; 648: 65–72.
Wiegmans AP, Al-Ejeh F, Chee N, et al. RAD51 supports triple negative breast cancer metastasis. Oncotarget 2014; 5: 3261.
Liu Y, Burness ML, Martin-Trevino R, et al. RAD51 mediates resistance of cancer stem cells to PARP inhibition in triple-negative breast cancer. Clin Cancer Res 2017; 23: 514–22.
Gasparini P, Lovat F, Fassan M, Casadei L, et al. Protective role of miR-155 in breast cancer through RAD51 targeting impairs homologous recombination after irradiation. Proc Natl Acad Sci USA 2014; 111: 4536–41.
Ward A, Khanna KK, Wiegmans AP. Targeting homologous recombination, new pre-clinical and clinical therapeutic combinations inhibiting RAD51. Cancer Treat Rev 2015; 41: 35–45.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Experimental Oncology
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
