Applications of Cytogenetics and Cytogenomics Evaluation techniques in cancer diagnosis: A review
Keywords:
cytogenetics, cytogenomics, cancer diagnosis, karyotyping, fluorescence in situ hybridization, next-generation sequencing, tumor heterogeneity, precision oncologyAbstract
Background: Cytogenetics and cytogenomics have revolutionized cancer diagnosis by revealing the underlying genetic alterations that characterize malignancies. The identification of chromosomal rearrangements, mutations, and DNA dosage abnormalities in cancer cells has enhanced our understanding of cancer as a genomic disease, enabling the detection of residual disease and improving patient prognosis. Aim: This review aims to explore the application of cytogenetic and cytogenomic evaluation techniques in cancer diagnostics. Methods: Through a detailed examination of traditional cytogenetic methods like karyotyping and fluorescence in situ hybridization (FISH), along with advanced genomic tools such as next-generation sequencing (NGS) and single-cell technologies, the review highlights their respective contributions to precision oncology. Findings: It also discusses the challenges posed by tumor heterogeneity and the need for individualized treatment approaches. The integration of cytogenetic and cytogenomic techniques provides critical insights into cancer heterogeneity, clonal evolution, and the identification of therapeutic targets, facilitating early diagnosis, prognosis, and personalized treatment plans. Conclusion: The advancement of high-throughput technologies has further accelerated the discovery of novel biomarkers, enhancing the precision of cancer diagnosis and treatment strategies.
Downloads
References
Pinkel, D.; Albertson, D.G. Array comparative genomic hybridization and its applications in cancer. Nat. Genet. 2005, 37, S11–S17. DOI: https://doi.org/10.1038/ng1569
Oehler, V.G.; Yeung, K.Y.; Choi, Y.E.; Bumgarner, R.E.; Raftery, A.E.; Radich, J.P. The derivation of diagnostic markers of chronic myeloid leukemia progression from microarray data. Blood 2009, 114, 3292–3298. DOI: https://doi.org/10.1182/blood-2009-03-212969
Bernheim, A. Cytogenomics of cancers: From chromosome to sequence. Mol. Oncol. 2010, 4, 309–322. DOI: https://doi.org/10.1016/j.molonc.2010.06.003
Thompson, C.B. Attacking cancer at its root. Cell 2009, 138, 1051–1054. DOI: https://doi.org/10.1016/j.cell.2009.09.002
Chakravarthi, B.V.; Nepal, S.; Varambally, S. Genomic and Epigenomic Alterations in Cancer. Am. J. Pathol. 2016, 186, 1724–1735. DOI: https://doi.org/10.1016/j.ajpath.2016.02.023
McGranahan, N.; Swanton, C. Clonal heterogeneity and tumor evolution: Past, present, and the future. Cell 2017, 168, 613–628. DOI: https://doi.org/10.1016/j.cell.2017.01.018
Mody, R.J.; Wu, Y.M.; Lonigro, R.J.; Cao, X.; Roychowdhury, S.; Vats, P.; Frank, K.M.; Prensner, J.R.; Asangani, I.; Palanisamy, N.; et al. Integrative clinical sequencing in the management of refractory or relapsed cancer in youth. Jama 2015, 314, 913–925 DOI: https://doi.org/10.1001/jama.2015.10080
Heppt, M.V.; Siepmann, T.; Engel, J.; Schubert-Fritschle, G.; Eckel, R.; Mirlach, L.; Kirchner, T.; Jung, A.; Gesierich, A.; Ruzicka, T.; et al. Prognostic significance of BRAF and NRAS mutations in melanoma: A German study from routine care. BMC Cancer 2017, 17, 536. DOI: https://doi.org/10.1186/s12885-017-3529-5
Leemans, C. R., Snijders, P. J., & Brakenhoff, R. H. (2018). The molecular landscape of head and neck cancer. Nature Reviews Cancer, 18(5), 269-282. DOI: https://doi.org/10.1038/nrc.2018.11
Wan, T.S. Cancer cytogenetics: An introduction. In Cancer Cytogenetics; Humana Press: New York, NY, USA, 2017; Volume 1541, pp. 1–10. DOI: https://doi.org/10.1007/978-1-4939-6703-2_1
Gollin, S.M. Acquired chromosome abnormalities: The cytogenetics of cancer. In Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics; John Wiley & Sons, Ltd.: Hoboken, NJ, USA, 2005; pp. 1–14. DOI: https://doi.org/10.1002/047001153X.g102204
Das, K.; Tan, P. Molecular cytogenetics: Recent developments and applications in cancer. Clin. Genet. 2013, 84, 315–325. DOI: https://doi.org/10.1111/cge.12229
Cui, C.; Shu, W.; Li, P. Fluorescence in situ hybridization: Cell-based genetic diagnostic and research applications. Front. Cell Dev. Biol. 2016, 4, 89. DOI: https://doi.org/10.3389/fcell.2016.00089
Kearney, L. Molecular cytogenetics. Best Pract. Res. Clin. Haematol. 2001, 14, 645–669. DOI: https://doi.org/10.1053/beha.2001.0159
Weier, H.U.; Greulich-Bode, K.M.; Ito, Y.; Lersch, R.A.; Fung, J. FISH in cancer diagnosis and prognostication: From cause to course of disease. Expert Rev. Mol. Diagn. 2002, 2, 109–119. DOI: https://doi.org/10.1586/14737159.2.2.109
Dimashkieh, H.; Wolff, D.J.; Smith, T.M.; Houser, P.M.; Nietert, P.J.; Yang, J. Evaluation of urovysion and cytology for bladder cancer detection: A study of 1835 paired urine samples with clinical and histologic correlation. Cancer Cytopathol. 2013, 121, 591–597. DOI: https://doi.org/10.1002/cncy.21327
Ried, T.; Liyanage, M.; du Manoir, S.; Heselmeyer, K.; Auer, G.; Macville, M.; Schrock, E. Tumor cytogenetics revisited: Comparative genomic hybridization and spectral karyotyping. J. Mol. Med. 1997, 75, 801–814. DOI: https://doi.org/10.1007/s001090050169
Davies, J.J.; Wilson, I.M.; Lam, W.L. Array CGH technologies and their applications to cancer genomes. Chromosome Res. 2005, 13, 237–248. DOI: https://doi.org/10.1007/s10577-005-2168-x
Solinas-Toldo, S.; Lampel, S.; Stilgenbauer, S.; Nickolenko, J.; Benner, A.; Dohner, H.; Cremer, T.; Lichter, P. Matrix-based comparative genomic hybridization: Biochips to screen for genomic imbalances. Genes Chromosomes Cancer 1997, 20, 399–407. DOI: https://doi.org/10.1002/(SICI)1098-2264(199712)20:4<399::AID-GCC12>3.3.CO;2-L
Pollack, J.R.; Perou, C.M.; Alizadeh, A.A.; Eisen, M.B.; Pergamenschikov, A.; Williams, C.F.; Jeffrey, S.S.; Botstein, D.; Brown, P.O. Genome-wide analysis of DNA copy-number changes using cDNA microarrays. Nat. Genet. 1999, 23, 41–46. DOI: https://doi.org/10.1038/12640
Lockwood, W.W.; Chari, R.; Chi, B.; Lam, W.L. Recent advances in array comparative genomic hybridization technologies and their applications in human genetics. Eur. J. Hum. Genet. 2006, 14, 139–148. DOI: https://doi.org/10.1038/sj.ejhg.5201531
Li, P.; Cui, C. A broader view of cancer cytogenetics: From nuclear aberrations to cytogenomic abnormalities. J. Mol. Genet. Med. 2017, 10, e108. DOI: https://doi.org/10.4172/1747-0862.1000E108
Metzker, M.L. Sequencing technologies—The next generation. Nat. Rev. Genet. 2010, 11, 31–46. DOI: https://doi.org/10.1038/nrg2626
Homig-Holzel, C.; Savola, S. Multiplex ligation-dependent probe amplification (MLPA) in tumor diagnostics and prognostics. Diagn. Mol. Pathol. 2012, 21, 189–206. DOI: https://doi.org/10.1097/PDM.0b013e3182595516
Ribeiro, I.P.; Marques, F.; Caramelo, F.; Pereira, J.; Patricio, M.; Prazeres, H.; Ferrao, J.; Juliao, M.J.; Castelo-Branco, M.; de Melo, J.B.; et al. Genetic gains and losses in oral squamous cell carcinoma: Impact on clinical management. Cell. Oncol. 2014, 37, 29–39. DOI: https://doi.org/10.1007/s13402-013-0161-5
Ribeiro, I.P.; Marques, F.; Caramelo, F.; Ferrao, J.; Prazeres, H.; Juliao, M.J.; Rifi, W.; Savola, S.; de Melo, J.B.; Baptista, I.P.; et al. Genetic imbalances detected by multiplex ligation-dependent probe amplification in a cohort of patients with oral squamous cell carcinoma-the first step towards clinical personalized medicine. Tumour Biol. 2014, 35, 4687–4695. DOI: https://doi.org/10.1007/s13277-014-1614-9
Xuan, J.; Yu, Y.; Qing, T.; Guo, L.; Shi, L. Next-generation sequencing in the clinic: Promises and challenges. Cancer Lett. 2013, 340, 284–295. DOI: https://doi.org/10.1016/j.canlet.2012.11.025
Kamps, R.; Brandao, R.D.; Bosch, B.J.; Paulussen, A.D.; Xanthoulea, S.; Blok, M.J.; Romano, A. Next-generation sequencing in oncology: Genetic diagnosis, risk prediction and cancer classification. Int. J. Mol. Sci. 2017, 18, 308. DOI: https://doi.org/10.3390/ijms18020308
Parisi, F.; Micsinai, M.; Strino, F.; Ariyan, S.; Narayan, D.; Bacchiocchi, A.; Cheng, E.; Xu, F.; Li, P.; Kluger, H.; et al. Integrated analysis of tumor samples sheds light on tumor heterogeneity. Yale J. Biol. Med. 2012, 85, 347–361.
Navin, N.E. The first five years of single-cell cancer genomics and beyond. Genome Res. 2015, 25, 1499–1507 DOI: https://doi.org/10.1101/gr.191098.115
Liang, S.B.; Fu, L.W. Application of single-cell technology in cancer research. Biotechnol. Adv. 2017, 35, 443–449. DOI: https://doi.org/10.1016/j.biotechadv.2017.04.001
Navin, N.E. Cancer genomics: One cell at a time. Genome Biol. 2014, 15, 452. DOI: https://doi.org/10.1186/s13059-014-0452-9
Sierant, M.C.; Choi, J. Single-cell ssequencing in cancer: Recent applications to immunogenomics and multi-omics tools. Genom. Inform. 2018, 16, e17. DOI: https://doi.org/10.5808/GI.2018.16.4.e17
Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell 2011, 144, 646–674. DOI: https://doi.org/10.1016/j.cell.2011.02.013
Surrey, L.F.; Luo, M.; Chang, F.; Li, M.M. The genomic era of clinical oncology: Integrated genomic analysis for precision cancer care. Cytogenet. Genome Res. 2016, 150, 162–175. DOI: https://doi.org/10.1159/000454655
Albertson, D.G.; Collins, C.; McCormick, F.; Gray, J.W. Chromosome aberrations in solid tumors. Nat. Genet. 2003, 34, 369–376. DOI: https://doi.org/10.1038/ng1215
Mitelman, F.; Johansson, B.; Mandahl, N.; Mertens, F. Clinical significance of cytogenetic findings in solid tumors. Cancer Genet. Cytogenet. 1997, 95, 1–8. DOI: https://doi.org/10.1016/S0165-4608(96)00252-X
Grade, M.; Difilippantonio, M.J.; Camps, J. Patterns of chromosomal aberrations in solid tumors. Recent Results Cancer Res. 2015, 200, 115–142. DOI: https://doi.org/10.1007/978-3-319-20291-4_6
Stratton, M.R.; Campbell, P.J.; Futreal, P.A. The cancer genome. Nature 2009, 458, 719–724. DOI: https://doi.org/10.1038/nature07943
Miller, D.G. On the nature of susceptibility to cancer. The presidential address. Cancer 1980, 46, 1307–1318. DOI: https://doi.org/10.1002/1097-0142(19800915)46:6<1307::AID-CNCR2820460602>3.0.CO;2-6
Talbot, S.J.; Crawford, D.H. Viruses and tumours-an update. Eur. J. Cancer 2004, 40, 1998–2005. DOI: https://doi.org/10.1016/j.ejca.2003.11.039
Min, J.W.; Kim, W.J.; Han, J.A.; Jung, Y.J.; Kim, K.T.; Park, W.Y.; Lee, H.O.; Choi, S.S. Identification of distinct tumor subpopulations in lung adenocarcinoma via single-cell RNA-seq. PLoS ONE 2015, 10, e0135817. DOI: https://doi.org/10.1371/journal.pone.0135817
Dagogo-Jack, I.; Shaw, A.T. Tumour heterogeneity and resistance to cancer therapies. Nat. Rev. Clin. Oncol. 2018, 15, 81–94. DOI: https://doi.org/10.1038/nrclinonc.2017.166
Greaves, M.; Maley, C.C. Clonal evolution in cancer. Nature 2012, 481, 306–313. DOI: https://doi.org/10.1038/nature10762
Khoo, B.L.; Chaudhuri, P.K.; Ramalingam, N.; Tan, D.S.; Lim, C.T.; Warkiani, M.E. Single-cell profiling approaches to probing tumor heterogeneity. Int. J. Cancer 2016, 139, 243–255. DOI: https://doi.org/10.1002/ijc.30006
Greaves, M. Evolutionary determinants of cancer. Cancer Discov. 2015, 5, 806–820. DOI: https://doi.org/10.1158/2159-8290.CD-15-0439
Raynaud, F.; Mina, M.; Tavernari, D.; Ciriello, G. Pan-cancer inference of intra-tumor heterogeneity reveals associations with different forms of genomic instability. PLoS Genet. 2018, 14, e1007669. DOI: https://doi.org/10.1371/journal.pgen.1007669
Kelloff, G.J.; Sigman, C.C. Cancer biomarkers: Selecting the right drug for the right patient. Nat. Rev. Drug Discov. 2012, 11, 201–214. DOI: https://doi.org/10.1038/nrd3651
Navin, N.E.; Hicks, J. Tracing the tumor lineage. Mol. Oncol. 2010, 4, 267–283. DOI: https://doi.org/10.1016/j.molonc.2010.04.010
Sottoriva, A.; Spiteri, I.; Piccirillo, S.G.; Touloumis, A.; Collins, V.P.; Marioni, J.C.; Curtis, C.; Watts, C.; Tavare, S. Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics. Proc. Natl. Acad. Sci. USA 2013, 110, 4009–4014. DOI: https://doi.org/10.1073/pnas.1219747110
Tan, D.S.; Camilleri-Broet, S.; Tan, E.H.; Alifano, M.; Lim, W.T.; Bobbio, A.; Zhang, S.; Ng, Q.S.; Ang, M.K.; Iyer, N.G.; et al. Intertumor heterogeneity of non-small-cell lung carcinomas revealed by multiplexed mutation profiling and integrative genomics. Int. J. Cancer 2014, 135, 1092–1100. DOI: https://doi.org/10.1002/ijc.28750
Gerlinger, M.; Rowan, A.J.; Horswell, S.; Math, M.; Larkin, J.; Endesfelder, D.; Gronroos, E.; Martinez, P.; Matthews, N.; Stewart, A.; et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N. Engl. J. Med. 2012, 366, 883–892. DOI: https://doi.org/10.1056/NEJMoa1113205
Polyak, K. Heterogeneity in breast cancer. J. Clin. Investig. 2011, 121, 3786–3788. DOI: https://doi.org/10.1172/JCI60534
Brocks, D.; Assenov, Y.; Minner, S.; Bogatyrova, O.; Simon, R.; Koop, C.; Oakes, C.; Zucknick, M.; Lipka, D.B.; Weischenfeldt, J.; et al. Intratumor DNA methylation heterogeneity reflects clonal evolution in aggressive prostate cancer. Cell Rep. 2014, 8, 798–806. DOI: https://doi.org/10.1016/j.celrep.2014.06.053
Fisher, R.; Pusztai, L.; Swanton, C. Cancer heterogeneity: Implications for targeted therapeutics. Br. J. Cancer 2013, 108, 479–485. DOI: https://doi.org/10.1038/bjc.2012.581
Chatterjee, S.K.; Zetter, B.R. Cancer biomarkers: Knowing the present and predicting the future. Future Oncol. 2005, 1, 37–50. DOI: https://doi.org/10.1517/14796694.1.1.37
Ribeiro, I.P.; Barroso, L.; Marques, F.; Melo, J.B.; Carreira, I.M. Early detection and personalized treatment in oral cancer: The impact of omics approaches. Mol. Cytogenet. 2016, 9, 85. DOI: https://doi.org/10.1186/s13039-016-0293-1
Goossens, N.; Nakagawa, S.; Sun, X.; Hoshida, Y. Cancer biomarker discovery and validation. Trans. Cancer Res. 2015, 4, 256–269.
Roukos, D.H. Integrated clinical genomics: New horizon for diagnostic and biomarker discoveries in cancer. Expert Rev. Mol. Diagn. 2013, 13, 1–4. DOI: https://doi.org/10.1586/erm.12.132
Ribeiro, I.P.; Caramelo, F.; Marques, F.; Domingues, A.; Mesquita, M.; Barroso, L.; Prazeres, H.; Juliao, M.J.; Baptista, I.P.; Ferreira, A.; et al. WT1, MSH6, GATA5 and PAX5 as epigenetic oral squamous cell carcinoma biomarkers—A short report. Cell. Oncol. 2016, 39, 573–582. DOI: https://doi.org/10.1007/s13402-016-0293-5
Paris, P.L.; Andaya, A.; Fridlyand, J.; Jain, A.N.; Weinberg, V.; Kowbel, D.; Brebner, J.H.; Simko, J.; Watson, J.E.; Volik, S.; et al. Whole genome scanning identifies genotypes associated with recurrence and metastasis in prostate tumors. Hum. Mol. Genet. 2004, 13, 1303–1313. DOI: https://doi.org/10.1093/hmg/ddh155
Callagy, G.; Pharoah, P.; Chin, S.F.; Sangan, T.; Daigo, Y.; Jackson, L.; Caldas, C. Identification and validation of prognostic markers in breast cancer with the complementary use of array-CGH and tissue microarrays. J. Pathol. 2005, 205, 388–396. DOI: https://doi.org/10.1002/path.1694
Weiss, M.M.; Kuipers, E.J.; Postma, C.; Snijders, A.M.; Pinkel, D.; Meuwissen, S.G.; Albertson, D.; Meijer, G.A. Genomic alterations in primary gastric adenocarcinomas correlate with clinicopathological characteristics and survival. Cell. Oncol. 2004, 26, 307–317. DOI: https://doi.org/10.1155/2004/454238
Rubio-Moscardo, F.; Climent, J.; Siebert, R.; Piris, M.A.; Martin-Subero, J.I.; Nielander, I.; Garcia-Conde, J.; Dyer, M.J.; Terol, M.J.; Pinkel, D.; et al. Mantle-cell lymphoma genotypes identified with CGH to BAC microarrays define a leukemic subgroup of disease and predict patient outcome. Blood 2005, 105, 4445–4454. DOI: https://doi.org/10.1182/blood-2004-10-3907
Romond, E.H.; Perez, E.A.; Bryant, J.; Suman, V.J.; Geyer, C.E., Jr.; Davidson, N.E.; Tan-Chiu, E.; Martino, S.; Paik, S.; Kaufman, P.A.; et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N. Engl. J. Med. 2005, 353, 1673–1684. DOI: https://doi.org/10.1056/NEJMoa052122
Bang, Y.J.; Van Cutsem, E.; Feyereislova, A.; Chung, H.C.; Shen, L.; Sawaki, A.; Lordick, F.; Ohtsu, A.; Omuro, Y.; Satoh, T.; et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): A phase 3, open-label, randomised controlled trial. Lancet 2010, 376, 687–697. DOI: https://doi.org/10.1016/S0140-6736(10)61121-X
Kantarjian, H.; Sawyers, C.; Hochhaus, A.; Guilhot, F.; Schiffer, C.; Gambacorti-Passerini, C.; Niederwieser, D.; Resta, D.; Capdeville, R.; Zoellner, U.; et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N. Engl. J. Med. 2002, 346, 645–652. DOI: https://doi.org/10.1056/NEJMoa011573
Amado, R.G.; Wolf, M.; Peeters, M.; Van Cutsem, E.; Siena, S.; Freeman, D.J.; Juan, T.; Sikorski, R.; Suggs, S.; Radinsky, R.; et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J. Clin. Oncol. 2008, 26, 1626–1634. DOI: https://doi.org/10.1200/JCO.2007.14.7116
Dematteo, R.P.; Ballman, K.V.; Antonescu, C.R.; Maki, R.G.; Pisters, P.W.; Demetri, G.D.; Blackstein, M.E.; Blanke, C.D.; von Mehren, M.; Brennan, M.F.; et al. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: A randomised, double-blind, placebo-controlled trial. Lancet 2009, 373, 1097–1104. DOI: https://doi.org/10.1016/S0140-6736(09)60500-6
Pao, W.; Girard, N. New driver mutations in non-small-cell lung cancer. Lancet. Oncol. 2011, 12, 175–180. DOI: https://doi.org/10.1016/S1470-2045(10)70087-5
Chapman, P.B.; Hauschild, A.; Robert, C.; Haanen, J.B.; Ascierto, P.; Larkin, J.; Dummer, R.; Garbe, C.; Testori, A.; Maio, M.; et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N. Engl. J. Med. 2011, 364, 2507–2516. DOI: https://doi.org/10.1056/NEJMoa1103782
Chistiakov, D.A.; Myasoedova, V.A.; Grechko, A.V.; Melnichenko, A.A.; Orekhov, A.N. New biomarkers for diagnosis and prognosis of localized prostate cancer. Semin. Cancer Biol. 2018, 52, 9–16. DOI: https://doi.org/10.1016/j.semcancer.2018.01.012
Paik, S.; Shak, S.; Tang, G.; Kim, C.; Baker, J.; Cronin, M.; Baehner, F.L.; Walker, M.G.; Watson, D.; Park, T.; et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N. Engl. J. Med. 2004, 351, 2817–2826. DOI: https://doi.org/10.1056/NEJMoa041588
Brandão, M., Pondé, N., & Piccart-Gebhart, M. (2018). Mammaprint™: a comprehensive review. Future oncology, 15(2), 207-224. DOI: https://doi.org/10.2217/fon-2018-0221
Boutros, P.C. The path to routine use of genomic biomarkers in the cancer clinic. Genome Res. 2015, 25, 1508–1513. DOI: https://doi.org/10.1101/gr.191114.115
Ma, M.; Zhu, H.; Zhang, C.; Sun, X.; Gao, X.; Chen, G. ″Liquid biopsy″-ctDNA detection with great potential and challenges. Ann. Transl. Med. 2015, 3, 235.
Castro-Giner, F., Gkountela, S., Donato, C., Alborelli, I., Quagliata, L., Ng, C. K., ... & Aceto, N. (2018). Cancer diagnosis using a liquid biopsy: challenges and expectations. Diagnostics, 8(2), 31. DOI: https://doi.org/10.3390/diagnostics8020031
Kwapisz, D. The first liquid biopsy test approved. Is it a new era of mutation testing for non-small cell lung cancer? Ann. Transl. Med. 2017, 5, 46. DOI: https://doi.org/10.21037/atm.2017.01.32
Riethdorf, S.; O’Flaherty, L.; Hille, C.; Pantel, K. Clinical applications of the CellSearch platform in cancer patients. Adv. Drug Deliv. Rev. 2018, 125, 102–121 DOI: https://doi.org/10.1016/j.addr.2018.01.011
Published
How to Cite
Issue
Section
Copyright (c) 2019 International journal of health sciences

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Articles published in the International Journal of Health Sciences (IJHS) are available under Creative Commons Attribution Non-Commercial No Derivatives Licence (CC BY-NC-ND 4.0). Authors retain copyright in their work and grant IJHS right of first publication under CC BY-NC-ND 4.0. Users have the right to read, download, copy, distribute, print, search, or link to the full texts of articles in this journal, and to use them for any other lawful purpose.
Articles published in IJHS can be copied, communicated and shared in their published form for non-commercial purposes provided full attribution is given to the author and the journal. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
This copyright notice applies to articles published in IJHS volumes 4 onwards. Please read about the copyright notices for previous volumes under Journal History.








