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Genetic Association of rs2237572 Cyclin-Dependent Kinase 6 Gene with Breast Cancer in Iraq

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Abstract

This case–control study is aimed to evaluate serum concentration of Cyclin-Dependent Kinase 6 (CDK6) and the genetic association between rs2237572 CDK6 gene and breast cancer (BC) in Iraq. To attain this goal, 80 patients with BC as cases and 80 healthy individuals as controls were included. Further, BC patients were sorted according to the molecular classification into four subtypes of Luminal A, Luminal B, Her2/neu enriched and TPN. Serum concentration of CDK6 enzyme, allelic and genotypic frequencies of rs2237572 CDK6, and the occurrence of BC phenotype and its subtypes in the studied population were investigated. ELISA technique was used to perform the biochemical testing, while the molecular analysis was achieved by real-time PCR, high resolution melting analysis, conventional PCR, as well as sequencing analysis. The results revealed no significant difference in serum concentration of CDK6 enzyme between patients and healthy controls (p > 0.05). Also, no significant differences were shown between BC patients subtypes (p > 0.05). The rs2237572 CDK6 genotypes were associated with the BC and affirmed that allele C was inherited as a recessive risk factor. Moreover, a highly significant difference between patients’ subtypes in the genotypic frequency of rs2237572 (p < 0.01) was noted. Furthermore, the association of rs2237572 genotypes and CDK6 serum concentration in BC patients showed a considered significant difference between C/C and T/T, C/C and T/C and the CDK6 level (p < 0.05). Nevertheless, T/T and T/C did not show any significant difference with the CDK6 level. Hence, it was concluded that the rs2237572 of CDK6 gene is significantly correlated with BC.

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References

  1. Korkola J, Gray JW. Breast cancer genomes—form and function. Curr Opin Genet Dev. 2010;20:4–14.

    Article  CAS  Google Scholar 

  2. Al-owaidi DS, Algazally ME, Alawaad AS. Association of rs2069502 Cyclin-Dependent Kinase 4 gene with breast cancer. EuroMediterranean Biomed J. 2020;15:40–6.

    Google Scholar 

  3. Mora A, Taranta M, Zaki N, Badidi E, Cinti C, Capobianco E. Ensemble inference by integrative cancer networks. Front Genet. 2014;5:59.

    Article  Google Scholar 

  4. Kumar V, Abbas AK, Aster JC. Robbins basic pathology. 9th ed. Philadelphia: Elsevier; 2013.

    Google Scholar 

  5. Choi YJ, Anders L. Signaling through cyclin D-dependent kinases. Oncogene. 2014;33:1890–903.

    Article  CAS  Google Scholar 

  6. Dall’Acqua A, Sonego M, Pellizzari I, Pellarin I, Canzonieri V, D’Andrea S, et al. CDK6 protects epithelial ovarian cancer from platinum-induced death via FOXO3 regulation. EMBO Mol Med. 2017;9:1415–33. https://doi.org/10.15252/emmm.201607012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Burkhart DL, Sage J. Cellular mechanisms of tumour suppression by the retinoblastoma gene. Nat Rev Cancer. 2008;8:671–82.

    Article  CAS  Google Scholar 

  8. Murphy CG, Dickler MN. The role of CDK4/6 inhibition in breast cancer. Oncologist. 2015;20:483–90. https://doi.org/10.1634/theoncologist.2014-0443.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Jing L, Su L, Ring BZ. Ethnic background and genetic variation in the evaluation of cancer risk: a systematic review. PLoS ONE. 2014;9:e97522. https://doi.org/10.1371/journal.pone.0097522.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Dai X, Li L, Liu X, Hu W, Yang Y, Bai Z. Cooperation of DLC1 and CDK6 affects breast cancer clinical outcome. G3 Genes Genomes Genet. 2015;5:81–91. https://doi.org/10.1534/g3.114.014894.

    Article  Google Scholar 

  11. Cai H, Xiang Y-B, Qu S, Long J, Cai Q, Gao J, et al. Association of genetic polymorphisms in cell-cycle control genes and susceptibility to endometrial cancer among Chinese women. Am J Epidemiol. 2011;173:1263–71. https://doi.org/10.1093/aje/kwr002.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Hashim HO, Al-Saadi AH, Haider AH, Zaidan HK. Association of Uromodulin rs13333226 and Angiotensinogen rs699 genes variants with essential hypertension in Arab Iraqis of Babylon province. Res J Pharm Biol Chem Sci. 2015;6:589–601.

    CAS  Google Scholar 

  13. Repaske DR, Phillips JA, Kirby LT, Tze WJ, D’ercole AJ, Battey J. Molecular analysis of autosomal dominant neurohypophyseal diabetes insipidus. J Clin Endocrinol Metab. 1990;70:752–7. https://doi.org/10.1210/jcem-70-3-752.

    Article  CAS  PubMed  Google Scholar 

  14. Gross-Bellard M, Oudet P, Chambon P. Isolation of high-molecular-weight DNA from mammalian cells. Eur J Biochem. 1973;36:32–8. https://doi.org/10.1111/j.1432-1033.1973.tb02881.x.

    Article  CAS  PubMed  Google Scholar 

  15. Sambrook J, Russell DW. Molecular cloning: a laboratory manual. 3rd ed. Oxford: Oxford University Press; 2001.

    Google Scholar 

  16. Altman DG. Practical statistics for medical research. Stat Med. 1991;10:1635–6.

    Article  Google Scholar 

  17. Chow LWC, Ho P. Hormonal receptor determination of 1052 Chinese breast cancers. J Surg Oncol. 2000;75:172–5. https://doi.org/10.1002/1096-9098%28200011%2975%3A3%3C172%3A%3AAID-JSO4%3E3.0.CO%3B2-A.

    Article  CAS  PubMed  Google Scholar 

  18. Guillemette C, Bélanger A, Lépine J. Metabolic inactivation of estrogens in breast tissue by UDP-glucuronosyltransferase enzymes: an overview. Breast Cancer Res. 2004;6:246. https://doi.org/10.1186/bcr936.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Zhu B. Functional role of estrogen metabolism in target cells: review and perspectives. Carcinogenesis. 1998;19:1–27. https://doi.org/10.1093/carcin/19.1.1.

    Article  PubMed  Google Scholar 

  20. Riza E, Dos Santos SI, De Stavola B, Bradlow HL, Sepkovic DW, Linos D, et al. Urinary estrogen metabolites and mammographic parenchymal patterns in postmenopausal women. Cancer Epidemiol Biomark Prev. 2001;10:627–34.

    CAS  Google Scholar 

  21. Driver KE, Song H, Lesueur F, Ahmed S, Barbosa-Morais NL, Tyrer JP, et al. Association of single-nucleotide polymorphisms in the cell cycle genes with breast cancer in the British population. Carcinogenesis. 2008;29:333–41. https://doi.org/10.1093/carcin/bgm284.

    Article  CAS  PubMed  Google Scholar 

  22. Aierken K, Dong Z, Abulimiti T, Zhang Y, Abuduxikuer G, Tuerxun G, et al. CDK6 3’UTR polymorphisms alter the susceptibility to cervical cancer among Uyghur females. Mol Genet Genom Med. 2019;7:e626. https://doi.org/10.1002/mgg3.626.

    Article  CAS  Google Scholar 

  23. Mendrzyk F, Radlwimmer B, Joos S, Kokocinski F, Benner A, Stange DE, et al. Genomic and protein expression profiling identifies CDK6 as novel independent prognostic marker in medulloblastoma. J Clin Oncol. 2005;23:8853–62. https://doi.org/10.1200/JCO.2005.02.8589.

    Article  CAS  PubMed  Google Scholar 

  24. García-Reyes B, Kretz A-L, Ruff J-P, von Karstedt S, Hillenbrand A, Knippschild U, et al. The emerging role of cyclin-dependent kinases (CDKs) in pancreatic ductal adenocarcinoma. Int J Mol Sci. 2018;19:3219.

    Article  Google Scholar 

  25. Whelan AJ, Bartsch D, Goodfellow PJ. A familial syndrome of pancreatic cancer and melanoma with a mutation in the CDKN2 tumor-suppressor gene. N Engl J Med. 1995;333:975–7. https://doi.org/10.1056/NEJM199510123331505.

    Article  CAS  PubMed  Google Scholar 

  26. Ma H, Chen J, Pan S, Dai J, Jin G, Hu Z, et al. Potentially functional polymorphisms in cell cycle genes and the survival of non-small cell lung cancer in a Chinese population. Lung Cancer. 2011;73:32–7.

    Article  Google Scholar 

  27. Sherr CJ, Beach D, Shapiro GI. Targeting CDK4 and CDK6: from discovery to therapy. Cancer Discov. 2016;6:353–67.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

I would like to thank all the people who aided and encouraged us in this work, particularly, the staff of the Babylon Oncology Center in Marjan Medical City and Consulting Clinic for Early Detection of Breast Cancer in Hilla Teaching Hospital for their kind assistance and help during sample collection.

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The authors received no financial support for the research.

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Author notes

  1. Moaed E. Algazally

    Present address: University of Al-Ameed, Karbala, Iraq

Authors and Affiliations

  1. Department of Clinical Biochemistry, College of Medicine, Babylon University, Hilla, 51002, Iraq

    Dalya Sh. Al-owaidi & Moaed E. Algazally

  2. Department of Internal Medicine, College of Medicine, University of Babylon, Hilla, Iraq

    Alaa Sadeq Alawaad

Authors
  1. Dalya Sh. Al-owaidi
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  2. Moaed E. Algazally
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  3. Alaa Sadeq Alawaad
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Contributions

SA carried out the molecular genetic studies, sequence alignment, immunoassays and drafted the manuscript. EA participated in the study design and coordination and helped to draft the manuscript. SA conceived of the study and participated in the study design. All the authors read and approved the final manuscript.

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Correspondence to Dalya Sh. Al-owaidi.

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Al-owaidi, D.S., Algazally, M.E. & Alawaad, A.S. Genetic Association of rs2237572 Cyclin-Dependent Kinase 6 Gene with Breast Cancer in Iraq. Ind J Clin Biochem 36, 304–311 (2021). https://doi.org/10.1007/s12291-020-00895-5

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  • DOI: https://doi.org/10.1007/s12291-020-00895-5

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