Research Article

Leukocyte telomere length and hTERT genetic polymorphism rs2735940 influence the renal cell carcinoma clinical outcome

Molecular Oncology & Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Rua António Bernardino de Almeida, 4200-072 Porto, Portugal

Department of Research, LPCC-Portuguese League Against Cancer (NRNorte), Estrada Interior da Circunvalação 6657, 4200-172 Porto, Portugal

ICBAS, Abel Salazar Institute for The Biomedical Sciences, University of Porto, Portugal

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Francisca Dias

Molecular Oncology & Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Rua António Bernardino de Almeida, 4200-072 Porto, Portugal

ICBAS, Abel Salazar Institute for The Biomedical Sciences, University of Porto, Portugal

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Telma Resende

Molecular Oncology & Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Rua António Bernardino de Almeida, 4200-072 Porto, Portugal

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Inês Nogueira

Molecular Oncology & Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Rua António Bernardino de Almeida, 4200-072 Porto, Portugal

Department of Research, LPCC-Portuguese League Against Cancer (NRNorte), Estrada Interior da Circunvalação 6657, 4200-172 Porto, Portugal

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Jorge Oliveira

Department of Urology, Portuguese Oncology Institute of Porto (IPO-Porto), Rua António Bernardino de Almeida, 4200-072 Porto, Portugal

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Joaquina Maurício

Department of Medical Oncology, Portuguese Oncology Institute of Porto (IPO-Porto), Rua António Bernardino de Almeida, 4200-072 Porto, Portugal

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Ana L Teixeira

*Author for correspondence: Tel.: +351 22 508 4000; Ext.: 5410; Fax: +351 22 508 4001;

E-mail Address: ana.luisa.teixeira@ipoporto.min-saude.pt

Molecular Oncology & Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Rua António Bernardino de Almeida, 4200-072 Porto, Portugal

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Rui Medeiros

Molecular Oncology & Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Rua António Bernardino de Almeida, 4200-072 Porto, Portugal

Department of Research, LPCC-Portuguese League Against Cancer (NRNorte), Estrada Interior da Circunvalação 6657, 4200-172 Porto, Portugal

FMUP, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal

CEBIMED, Faculty of Health Sciences, Fernando Pessoa University, Praça de 9 de Abril 349, 4249-004 Porto, Portugal

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Published Online:18 May 2020https://doi.org/10.2217/fon-2019-0795

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Abstract

Aim: Analysis of the genetic hTERT-1327 C>T (rs2735940) influence on leukocyte telomere length (LTL) and tumor development, progression and overall survival in renal cell carcinoma (RCC) patients. Materials & methods: Using leukocyte DNA of RCC patients and healthy individuals, LTL measurement and allelic discrimination of rs2735940 was performed by real-time PCR. Results: RCC patients showed shorter LTL than healthy individuals and LTL increased with clinical stage. CC+TC genotypes healthy carriers’ presented shorter LTL. However, no statistical association between the different genotypes and RCC risk. Nevertheless, CC homozygous presented a reduced time to disease progression and a lower overall survival. The use of hTERT-1327 single nucleotide polymorphism information increased the capacity to predict risk for RCC progression. Conclusion: In fact, in healthy individuals, hTERT-1327 CC+TC genotypes were associated with shorter LTL, and this single nucleotide polymorphism was associated with time to disease progression, being a promising potential prognosis biomarker to be used in the future.

Graphical abstract

The potential of the genetic polymorphism hTERT-1327 C>T (rs2735940) as a prognosis biomarker and the influence of leucocyte telomere length in renal cell carcinoma (RCC). RCC patients showed shorter leucocyte telomere length than healthy individuals. CC+CT genotypes of hTERT-1327 C>T genetic polymorphism are associated with shorter telomeres in healthy individuals and RCC patients with CC genotype show shorter time to disease progression interval and worse overall survival.

Keywords:

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Vol. 16, No. 18

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History

Received 3 December 2019

Accepted 17 April 2020

Published online 18 May 2020

Published in print June 2020

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Keywords

Author contributions

The work presented here was carried out in collaboration between all the authors. M Morais, F Dias and AL Teixeira designed the work. M Morais, T Resende and I Nogueira have performed the laboratory experiments. J Oliveira and J Maurício recruited the patients and collected the blood samples. M Morais, F Dias and AL Teixeira analyzed and interpreted the data. M Morais and AL Teixeira wrote the paper. AL Teixeira and R Medeiros revised the manuscript critically. R Medeiros supervised all the work. All the authors approved the final manuscript.

Acknowledgments

The authors thank to FCT – Fundação para a Ciência e Tecnologia (Portuguese Foundation for Science and Technology), Liga Portuguesa Contra o Cancro – Núcleo Regional do Norte – LPCC-NRN (Portuguese League Against Cancer- North Branch) and the nursing team of Urology Department from Portuguese Oncology Institute of Porto (IPO-Porto).

Financial & competing interests disclosure

M Morais and I Nogueira are recipients of a research scholarship awarded by LPCC-NRN. F Dias is a recipient of a research fellow from the project NORTE-01-0145-FEDER-000027, supported by Norte Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This project was also funded by the Research Center of the Portuguese Oncology Institute of Porto [CI-IPOP 21-2015]. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Data availability statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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