Telomere length in peripheral blood lymphocytes related to genetic variation in telomerase, prognosis and clinicopathological features in breast cancer patients.


Journal

Mutagenesis
ISSN: 1464-3804
Titre abrégé: Mutagenesis
Pays: England
ID NLM: 8707812

Informations de publication

Date de publication:
31 12 2020
Historique:
received: 23 07 2020
accepted: 06 11 2020
pubmed: 29 12 2020
medline: 20 8 2021
entrez: 28 12 2020
Statut: ppublish

Résumé

Disruption of telomere length (TL) homeostasis in peripheral blood lymphocytes has been previously assessed as a potential biomarker of breast cancer (BC) risk. The present study addressed the relationship between lymphocyte TL (LTL), prognosis and clinicopathological features in the BC patients since these associations are insufficiently explored at present. LTL was measured in 611 BC patients and 154 healthy controls using the monochrome multiplex quantitative Polymerase Chain Reaction assay. In addition, we genotyped nine TL-associated single-nucleotide polymorphisms that had been identified through genome-wide association studies. Our results showed that the patients had significantly (P = 0.001, Mann-Whitney U-test) longer LTL [median (interquartile range); 1.48 (1.22-1.78)] than the healthy controls [1.27 (0.97-1.82)]. Patients homozygous (CC) for the common allele of hTERT rs2736108 or the variant allele (CC) of hTERC rs16847897 had longer LTL. The latter association remained statistically significant in the recessive genetic model after the Bonferroni correction (P = 0.004, Wilcoxon two-sample test). We observed no association between LTL and overall survival or relapse-free survival of the patients. LTL did not correlate with cancer staging based on Union for International Cancer Control (UICC), The tumor node metastasis (TNM) staging system classification, tumour grade or molecular BC subtypes. Overall, we observed an association between long LTL and BC disease and an association of the hTERC rs16847897 CC genotype with increased LTL. However, no association between LTL, clinicopathological features and survival of the patients was found.

Identifiants

pubmed: 33367858
pii: 6050628
doi: 10.1093/mutage/geaa030
doi:

Substances chimiques

Biomarkers, Tumor 0
telomerase RNA 0
RNA 63231-63-0
TERT protein, human EC 2.7.7.49
Telomerase EC 2.7.7.49

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

491-497

Informations de copyright

© The Author(s) 2020. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society.All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Auteurs

Michal Kroupa (M)

Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska, Prague, Czech Republic.
Faculty of Medicine and Biomedical Center in Pilsen, Charles University in Prague, Husova, Pilsen, Czech Republic.

Sivaramakrishna Rachakonda (S)

Division of Functional Genome Analysis, German Cancer Research Center (DKFZ), Im Neuenheimer Feld, Heidelberg, Germany.

Veronika Vymetalkova (V)

Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska, Prague, Czech Republic.
Faculty of Medicine and Biomedical Center in Pilsen, Charles University in Prague, Husova, Pilsen, Czech Republic.
Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Albertov, Prague, Czech Republic.

Kristyna Tomasova (K)

Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska, Prague, Czech Republic.
Faculty of Medicine and Biomedical Center in Pilsen, Charles University in Prague, Husova, Pilsen, Czech Republic.

Vaclav Liska (V)

Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska, Prague, Czech Republic.
Faculty of Medicine and Biomedical Center in Pilsen, Charles University in Prague, Husova, Pilsen, Czech Republic.

Sona Vodenkova (S)

Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska, Prague, Czech Republic.
Department of Medical Genetics, Third Faculty of Medicine, Charles University, Ruska, Prague, Czech Republic.

Andrea Cumova (A)

Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska, Prague, Czech Republic.
Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Albertov, Prague, Czech Republic.

Andrea Rossnerova (A)

Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska, Prague, Czech Republic.

Ludmila Vodickova (L)

Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska, Prague, Czech Republic.
Faculty of Medicine and Biomedical Center in Pilsen, Charles University in Prague, Husova, Pilsen, Czech Republic.
Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Albertov, Prague, Czech Republic.

Kari Hemminki (K)

Faculty of Medicine and Biomedical Center in Pilsen, Charles University in Prague, Husova, Pilsen, Czech Republic.
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld, Heidelberg, Germany.

Pavel Soucek (P)

Faculty of Medicine and Biomedical Center in Pilsen, Charles University in Prague, Husova, Pilsen, Czech Republic.

Rajiv Kumar (R)

Division of Functional Genome Analysis, German Cancer Research Center (DKFZ), Im Neuenheimer Feld, Heidelberg, Germany.

Pavel Vodicka (P)

Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska, Prague, Czech Republic.
Faculty of Medicine and Biomedical Center in Pilsen, Charles University in Prague, Husova, Pilsen, Czech Republic.
Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Albertov, Prague, Czech Republic.

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