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PMID: 38109000 Published · ppublish English Journal Article Review Research Support, N.I.H., Intramural

Telomere length and cancer risk: finding Goldilocks.

Biogerontology ·Vol. 25 ·No. 2 ·2024-00-00 ·Pages 265-278

Savage SA

Abstract

Telomeres are the nucleoprotein complex at chromosome ends essential in genomic stability. Baseline telomere length (TL) is determined by rare and common germline genetic variants but shortens with age and is susceptible to certain environmental exposures. Cellular senescence or apoptosis are normally triggered when telomeres reach a critically short length, but cancer cells overcome these protective mechanisms and continue to divide despite chromosomal instability. Rare germline variants in telomere maintenance genes cause exceedingly short telomeres for age (< 1st percentile) and the telomere biology disorders, which are associated with elevated risks of bone marrow failure, myelodysplastic syndrome, acute myeloid leukemia, and squamous cell carcinoma of the head/neck and anogenital regions. Long telomeres due to rare germline variants in the same or different telomere maintenance genes are associated with elevated risks of other cancers, such as chronic lymphocytic leukemia or sarcoma. Early epidemiology studies of TL in the general population lacked reproducibility but new methods, including creation of a TL polygenic score using common variants, have found longer telomeres associated with excess risks of renal cell carcinoma, glioma, lung cancer, and others. It has become clear that when it comes to TL and cancer etiology, not too short, not too long, but "just right" telomeres are important in minimizing cancer risk.

Keywords
Cancer Dyskeratosis congenita Genetic variant Polygenic inheritance Polygenic risk score Telomere Telomere biology disorder
MeSH Terms
Humans Reproducibility of Results Telomere/genetics Telomere Shortening Cellular Senescence Genomic Instability Telomerase/genetics Neoplasms/genetics,pathology
Chemicals
Telomerase
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Savage Sharon A ORCID
Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, 6E456, Bethesda, MD, 20892-6772, USA. [email protected].
Conflict of Interest

The author declares no competing interests.

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Article Info
Journal
Biogerontology
Abbr.
Biogerontology
ISSN
1573-6768
DOI
10.1007/s10522-023-10080-9
Email
[email protected]
Published
2024-00-00
Epub
2023-00-18
Pages
265-278
Language
English
Region
Netherlands
NLM ID
100930043
Subset
IM
External Links
PubMed source DOI: 10.1007/s10522-023-10080-9 View journal details
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