Cited by 484Telomeres, Telomerase, and SenescenceGenetics, Aging, and Longevity in Model OrganismsGenetic Associations and Epidemiology

The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index; none of the 19 sources its claims cite is checked for support yet.

Telomere Length and Risk of Incident Cancer and Cancer Mortality

Open access

Abstract

CONTEXT: Telomeres are essential to preserve the integrity of the genome. Critically short telomeres lead to replicative cell senescence and chromosomal instability and may thereby increase cancer risk. OBJECTIVE: To determine the association between baseline telomere length and incident cancer and cancer mortality. DESIGN, SETTING, AND PARTICIPANTS: Leukocyte telomere length was measured by quantitative polymerase chain reaction in 787 participants free of cancer at baseline in 1995 from the prospective, population-based Bruneck Study in Italy. MAIN OUTCOME MEASURES: Incident cancer and cancer mortality over a follow-up period of 10 years (1995-2005 with a follow-up rate of 100%). RESULTS: A total of 92 of 787 participants (11.7%) developed cancer (incidence rate, 13.3 per 1000 person-years). Short telomere length at baseline was associated with incident cancer independently of standard cancer risk factors (multivariable hazard ratio [HR] per 1-SD decrease in log(e)-transformed telomere length, 1.60; 95% confidence interval [CI], 1.30-1.98; P < .001). Compared with participants in the longest telomere length group, the multivariable HR for incident cancer was 2.15 (95% CI, 1.12-4.14) in the middle length group and 3.11 (95% CI, 1.65-5.84) in the shortest length group (P < .001). Incidence rates were 5.1 (95% CI, 2.9-8.7) per 1000 person-years in the longest telomere length group, 14.2 (95% CI, 10.0-20.1) per 1000 person-years in the middle length group, and 22.5 (95% CI, 16.9-29.9) per 1000 person-years in the shortest length group. The association equally applied to men and women and emerged as robust under a variety of circumstances. Furthermore, short telomere length was associated with cancer mortality (multivariable HR per 1-SD decrease in log(e)-transformed telomere length, 2.13; 95% CI, 1.58-2.86; P < .001) and individual cancer subtypes with a high fatality rate. CONCLUSION: In this study population, there was a statistically significant inverse relationship between telomere length and both cancer incidence and mortality.

Overview

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Written from the paper’s full text.

TL;DR

In the prospective, population-based Bruneck Study, shorter baseline leukocyte telomere length was associated with higher incident cancer and cancer mortality over 10 years. The association was independent of standard cancer risk factors and appeared stronger for fatal cancers.

Key findings

  • Among 787 cancer-free participants at baseline, 92 (11.7%) developed cancer over 10 years (incidence rate, 13.3 per 1000 person-years); 44 cancer deaths occurred (mortality rate, 6.2 per 1000 person-years).
  • Each 1-SD decrease in log e-transformed telomere length was associated with incident cancer (multivariable HR, 1.60; 95% CI, 1.30-1.98; P<.001) and cancer mortality (multivariable HR, 2.13; 95% CI, 1.58-2.86; P<.001).
  • Compared with the longest telomere length tertile, incident cancer HRs were 2.15 (95% CI, 1.12-4.14) in the middle tertile and 3.11 (95% CI, 1.65-5.84) in the shortest tertile; cancer mortality HRs were 5.63 (95% CI, 1.27-24.98) and 11.11 (95% CI, 2.61-47.36), respectively.
  • Incidence rates were 5.1, 14.2, and 22.5 per 1000 person-years across longest, middle, and shortest telomere tertiles; cancer mortality rates were 0.8, 6.0, and 12.9 per 1000 person-years, respectively.

Methods

  • Prospective, population-based cohort: the Bruneck Study in Italy; 787 participants free of cancer at the 1995 baseline, followed for 10 years (1995-2005) with 100% follow-up.
  • Leukocyte telomere length was measured by quantitative polymerase chain reaction and expressed as relative T/S ratio; analyses used log e-transformed T/S ratios and tertile groups.
  • Cox proportional hazard models estimated associations with incident cancer and cancer mortality, adjusted for age, sex, social class, smoking, alcohol, diabetes, physical activity, BMI, high-sensitivity C-reactive protein, vitamin D, LDL cholesterol, and in a second model interleukin 6 and chronic infection.

Limitations

  • The paper states the study population was entirely white, so findings cannot necessarily be extrapolated to other races and ethnicities.
  • The paper states the number of cases was limited to 92 incident cancers and 44 cancer deaths, and the sample was too small to precisely assess associations for each specific cancer type.
  • The paper states telomere length was measured in circulating blood leukocytes rather than distinct tissues, and fatal/nonfatal tumor classification was based on data through 2005 and subject to further refinement; the observational design also cannot by itself establish causality.

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Integrity signals

Registry

Crossref · 10.1001/jama.2010.897

Cites

37 of 37 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

22 Own result · 10 Not checked yet · 7 Own method · 5 Own interpretation

Verify all 19 references — free account

Show all 24 claims

  • It may state two separate claims as one. 15
  • The quote only partly states this claim. 1
  • Probably not a substantial claim. 9
20 of 20
  • The authors state this as an assumption.

    This is the first prospective, population-based study to estimate the impact of telomere length on overall cancer manifestation and mortality.

    “Toourknowledge,thisisthefirstprospective, population-based study to estimate the impact of telomere length on overall cancer manifestation and mortality.”
  • The paper relies on this without support.

    There is a considerable paucity of data regarding cancer mortality.

    “Moreover, there is a considerable paucity of data regarding cancer mortality.”
  • The paper relies on this without support.

    Few evaluations have been prospective in design and measured telomere length well in advance of cancer manifestation; all studies to date were conducted in selected patient groups or healthy volunteers recruited among health professionals.

    “Few evaluations have been prospective in design and have measured telomere length well in advance of cancer manifestation; all of the studies, to date, were conducted in selected patient groups or healthy volunteers re-cruited among health professionals.”
  • The paper relies on this without support.

    A variety of experimental and genetic studies support the hypothesis that telomere attrition contributes to the manifestation and dissemination of malignancies.

    “A variety of experimental and genetic studies support the hypothesis that telomere attrition contributes to the manifestation and dissemination of malignancies.”
4 of 4

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Citations

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Metadata

Authors
Willeit, P., Willeit, J., Mayr, A., Weger, S., Oberhollenzer, F., Brandstätter, A., Kronenberg, F., & Kiechl, S.
Affiliations
Innsbruck Medical University (AT)
Corresponding author
Kiechl, Stefan
Venue
JAMA
Published
2010-07-07
Volume
304
Issue
1
Pages
69
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
OpenAlex
W2035720189
Cited by
484
References
37
Citations by year
2026: 9 · 2025: 8 · 2024: 31 · 2023: 10 · 2022: 13 · 2021: 26 · 2020: 36 · 2019: 26 · 2018: 42 · 2017: 37 · 2016: 33 · 2015: 38 · 2014: 56 · 2013: 32 · 2012: 49
FWCI
25.78
Type
journal article
Language
en
Open access
Locations
  • JAMA (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
telomere length, leukocyte telomeres, cancer incidence, cancer mortality, short telomeres, chromosomal instability, Bruneck Study, cancer risk biomarkers, aging and cancer risk, sex differences in cancer risk, genetic susceptibility to cancer, cancer risk factors, cancer screening, early cancer detection
MeSH terms
Adult, Aged, Female, Humans, Italy, Leukocytes, Male, Middle Aged, Neoplasms, Prospective Studies, Risk, Polymerase Chain Reaction, Telomere

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