{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:40:30Z","timestamp":1791308430006,"version":"4.3.1"},"reference-count":28,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T00:00:00Z","timestamp":1706832000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>In this study, we examined 130 patients with pituitary adenomas (PAs) and 320 healthy subjects, using DNA samples from peripheral blood leukocytes purified through the DNA salting-out method. Real-time polymerase chain reaction (RT-PCR) was used to assess single nucleotide polymorphisms (SNPs) and relative leukocyte telomere lengths (RLTLs), while enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of TERF1, TERF2, TNKS2, CTC1, and ZNF676 in blood serum. Our findings reveal several significant associations. Genetic associations with pituitary adenoma occurrence: the TERF1 rs1545827 CT + TT genotypes were linked to 2.9-fold decreased odds of PA occurrence. Conversely, the TNKS2 rs10509637 GG genotype showed 6.5-fold increased odds of PA occurrence. Gender-specific genetic associations with PA occurrence: in females, the TERF1 rs1545827 CC + TT genotypes indicated 3.1-fold decreased odds of PA occurrence, while the TNKS2 rs10509637 AA genotype was associated with 4.6-fold increased odds. In males, the presence of the TERF1 rs1545827 T allele was associated with 2.2-fold decreased odds of PA occurrence, while the TNKS2 rs10509637 AA genotype was linked to a substantial 10.6-fold increase in odds. Associations with pituitary adenoma recurrence: the TNKS2 rs10509637 AA genotype was associated with 4.2-fold increased odds of PA recurrence. On the other hand, the TERF1 rs1545827 CT + TT genotypes were linked to 3.5-fold decreased odds of PA without recurrence, while the TNKS2 rs10509637 AA genotype was associated with 6.4-fold increased odds of PA without recurrence. Serum TERF2 and TERF1 levels: patients with PA exhibited elevated serum TERF2 levels compared to the reference group. Conversely, patients with PA had decreased TERF1 serum levels compared to the reference group. Relative leukocyte telomere length (RLTL): a significant difference in RLTL between the PA group and the reference group was observed, with PA patients having longer telomeres. Genetic associations with telomere shortening: the TERF1 rs1545827 T allele was associated with 1.4-fold decreased odds of telomere shortening. In contrast, the CTC1 rs3027234 TT genotype was linked to 4.8-fold increased odds of telomere shortening. These findings suggest a complex interplay between genetic factors, telomere length, and pituitary adenoma occurrence and recurrence, with potential gender-specific effects. Furthermore, variations in TERF1 and TNKS2 genes may play crucial roles in telomere length regulation and disease susceptibility.<\/jats:p>","DOI":"10.3390\/cancers16030643","type":"journal-article","created":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T09:42:32Z","timestamp":1706866952000},"page":"643","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Influence of Telomere-Related Gene Variants, Serum Levels, and Relative Leukocyte Telomere Length in Pituitary Adenoma Occurrence and Recurrence"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7469-8825","authenticated-orcid":false,"given":"Greta","family":"Gedvilaite","sequence":"first","affiliation":[{"name":"Laboratory of Ophthalmology, Neuroscience Institute, Lithuanian University of Health Sciences, Medical Academy, Eiveniu 2, LT-50161 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loresa","family":"Kriauciuniene","sequence":"additional","affiliation":[{"name":"Laboratory of Ophthalmology, Neuroscience Institute, Lithuanian University of Health Sciences, Medical Academy, Eiveniu 2, LT-50161 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arimantas","family":"Tamasauskas","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Lithuanian University of Health Sciences, Medical Academy, Eiveniu 2, LT-50161 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasa","family":"Liutkeviciene","sequence":"additional","affiliation":[{"name":"Laboratory of Ophthalmology, Neuroscience Institute, Lithuanian University of Health Sciences, Medical Academy, Eiveniu 2, LT-50161 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/j.wneu.2013.11.001","article-title":"Functional pituitary adenoma recurrence after surgical resection","volume":"81","author":"Ajlan","year":"2013","journal-title":"World Neurosurg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S113","DOI":"10.4103\/0028-3886.287678","article-title":"Modern Radiation Therapy for Pituitary Adenoma: Review of Techniques and Outcomes","volume":"68","author":"Gupta","year":"2020","journal-title":"Neurol. India"},{"key":"ref_3","first-page":"V05180331","article-title":"Pituitary adenoma","volume":"181","author":"Andersen","year":"2019","journal-title":"Ugeskr. Laeger."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1097\/MCO.0b013e32834121b1","article-title":"Telomeres, lifestyle, cancer, and aging","volume":"14","author":"Shammas","year":"2011","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ma, H., Zhou, Z., Wei, S., Liu, Z., Pooley, K.A., Dunning, A.M., Svenson, U., Roos, G., Hosgood, H.D., and Shen, M. (2011). Shortened Telomere Length Is Associated with Increased Risk of Cancer: A Meta-Analysis. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020466"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"827","DOI":"10.2147\/CIA.S256425","article-title":"Shelterin Complex at Telomeres: Implications in Ageing","volume":"15","author":"Mir","year":"2020","journal-title":"Clin. Interv. Aging"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/j.cell.2016.01.036","article-title":"Shelterin protects chromosome ends by compacting telomeric chromatin","volume":"164","author":"Bandaria","year":"2016","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1101\/gad.344044.120","article-title":"The end protection problem\u2014An unexpected twist in the tail","volume":"35","author":"Ruis","year":"2021","journal-title":"Genes Dev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.csbj.2016.04.002","article-title":"Structure and function of the telomeric CST complex","volume":"14","author":"Rice","year":"2016","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1038\/nrc3025","article-title":"Telomeric and extra-telomeric roles for telomerase and the telomere-binding proteins","volume":"11","author":"Blasco","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1128\/MCB.20.5.1659-1668.2000","article-title":"Control of Human Telomere Length by TRF1 and TRF2","volume":"20","author":"Smogorzewska","year":"2000","journal-title":"Mol. Cell. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/j.febslet.2012.02.020","article-title":"miR-20a promotes migration and invasion by regulating TNKS2 in human cervical cancer cells","volume":"586","author":"Kang","year":"2012","journal-title":"FEBS Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5385","DOI":"10.1093\/hmg\/dds382","article-title":"Genome-wide meta-analysis points to CTC1 and ZNF676 as genes regulating telomere homeostasis in humans","volume":"21","author":"Mangino","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Amir, M., Khan, P., Queen, A., Dohare, R., Alajmi, M.F., Hussain, A., Islam, A., Ahmad, F., and Hassan, I. (2020). Structural Features of Nucleoprotein CST\/Shelterin Complex Involved in the Telomere Maintenance and Its Association with Disease Mutations. Cells, 9.","DOI":"10.3390\/cells9020359"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.biocel.2004.10.012","article-title":"Cancer and aging: The importance of telomeres in genome maintenance","volume":"37","author":"Rodier","year":"2005","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"55","DOI":"10.3389\/fendo.2017.00055","article-title":"Transcriptome Analysis Showed a Differential Signature between Invasive and Non-invasive Corticotrophinomas","volume":"8","author":"Lerario","year":"2017","journal-title":"Front. Endocrinol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Gedvilaite, G., Vilkeviciute, A., Glebauskiene, B., Kriauciuniene, L., and Liutkeviciene, R. (2022). Molecular Markers of Telomerase Complex for Patients with Pituitary Adenoma. Brain Sci., 12.","DOI":"10.3390\/brainsci12080980"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/30.10.e47","article-title":"Telomere measurement by quantitative PCR","volume":"30","author":"Cawthon","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real time quantitative PCR and the method","volume":"25","author":"Livak","year":"2011","journal-title":"Methods"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Holesova, Z., Krasnicanova, L., Saade, R., P\u00f6s, O., Budis, J., Gazdarica, J., Repiska, V., and Szemes, T. (2023). Telomere Length Changes in Cancer: Insights on Carcinogenesis and Potential for Non-Invasive Diagnostic Strategies. Genes, 14.","DOI":"10.3390\/genes14030715"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/s10522-015-9551-6","article-title":"Population-specific association of genes for telomere-associated proteins with longevity in an Italian population","volume":"16","author":"Crocco","year":"2015","journal-title":"Biogerontology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3008","DOI":"10.1016\/j.ejca.2009.08.012","article-title":"Polymorphisms in telomere-associated genes, breast cancer susceptibility and prognosis","volume":"45","author":"Varadi","year":"2009","journal-title":"Eur. J. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6002672","DOI":"10.1155\/2022\/6002672","article-title":"Recurrence Rate and Exploration of Clinical Factors after Pituitary Adenoma Surgery: A Systematic Review and Meta-Analysis based on Computer Artificial Intelligence System","volume":"2022","author":"Zhang","year":"2022","journal-title":"Comput. Intell. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s10549-007-9622-8","article-title":"The expression of gene transcripts of telomere-associated genes in human breast cancer: Correlation with clinico-pathological parameters and clinical outcome","volume":"109","author":"Salhab","year":"2007","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Bhari, V.K., Kumar, D., Kumar, S., and Mishra, R. (2021). Shelterin complex gene: Prognosis and therapeutic vulnerability in cancer. Biochem. Biophys. Rep., 26.","DOI":"10.1016\/j.bbrep.2021.100937"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Morcos, Y.A.T., Najjar, G., Meessen, S., Witt, B., Azoitei, A., Kumar, M., Wakileh, G., Schwarz, K., Schrezenmeier, H., and Zengerling, F. (2019). A Novel Tissue and Stem Cell Specific TERF1 Splice Variant Is Downregulated in Tumour Cells. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010085"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1038\/s41379-020-0523-2","article-title":"Telomere length alterations and ATRX\/DAXX loss in pituitary adenomas","volume":"33","author":"Heaphy","year":"2020","journal-title":"Mod. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1038\/385740a0","article-title":"Control of telomere length by the human telomeric protein TRF1","volume":"385","year":"1997","journal-title":"Nature"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/3\/643\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:53:38Z","timestamp":1760104418000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/3\/643"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,2]]},"references-count":28,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["cancers16030643"],"URL":"https:\/\/doi.org\/10.3390\/cancers16030643","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,2]]}}}