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 accessAbstract
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.
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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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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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;PϽ.001)”
- Also stated in: § RESULTS · plain
“An association was seen between baseline telomere length and cancer mortality (multivariable HR per 1-SD decrease in log e -transformed telomere length, 2.13 [95% CI, 1.58-2.86];P Ͻ .001)”
§ Telomere Length and Risk of Incident Cancer and Cancer Mortality > Abstract
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In the paper
“Compared with participants with the longest telomere lengths, the multivariable HR for cancer mortality was 5.63 (95% CI, 1.27-24.98) in the middle length group and 11.11 (95% CI, 2.61-47.36) in the shortest length group (PϽ.001).”
§ Telomere Length and Risk of Incident Cancer and Cancer Mortality > RESULTS
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In the paper
“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 (PϽ.001).”
- Also stated in: § RESULTS · plain
“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 Ͻ.001).”
§ Telomere Length and Risk of Incident Cancer and Cancer Mortality > Abstract
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In the paper
“that surpassed the associations obtained for cardiovascular mortality (HR, 1.41 [95% CI, 1.01-1.96];P = .05)and mortality from other causes (HR, 1.57 [95% CI, 1.17-2.10];P = .003).”
§ Telomere Length and Risk of Incident Cancer and Cancer Mortality > RESULTS
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In the paper
“Compared with participants with the longest telomere lengths, the multivariable HR for cancer mortality was 5.63 (95% CI, 1.27-24.98) in the middle length group and 11.11 (95% CI, 2.61-47.36) in the shortest length group (PϽ.001).”
§ Telomere Length and Risk of Incident Cancer and Cancer Mortality > RESULTS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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;PϽ.001).”
- Also stated in: § RESULTS · plain
“The HR per 1-SD decrease in log etransformed telomere length for incident cancer was 1.60 (95% CI, 1.30-1.98;multivariable model, P Ͻ .001)”
§ Telomere Length and Risk of Incident Cancer and Cancer Mortality > Abstract
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In the paper
“that surpassed the associations obtained for cardiovascular mortality (HR, 1.41 [95% CI, 1.01-1.96];P = .05)and mortality from other causes (HR, 1.57 [95% CI, 1.17-2.10];P = .003).”
§ Telomere Length and Risk of Incident Cancer and Cancer Mortality > RESULTS
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In the paper
“Incidence rates were 5.1 per 1000 person-years in the longest telomere length group, 14.2 per 1000 person-years in the middle length group, and 22.5 per 1000 personyears in shortest length group.”
§ Telomere Length and Risk of Incident Cancer and Cancer Mortality > RESULTS
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In the paper
“Of note, telomere length was preferentially associated with individual cancers characterized by a high fatality rate such as gastric, lung, and ovarian cancer, but less so with tumors linked to better prognosis (see eFigure 4 at http://www .jama.com).”
- Also stated in: § COMMENT · hedged
“There was evidence of heterogeneous effects according to cancer type, whereby (1) tumors with a high fatality rate tended to exhibit more prominent relationships with telomere length (see eFigure 4 at http://www.jama.com)and ( 2) tumors with a more favorable prognosis showed modest or no associations.”
§ Telomere Length and Risk of Incident Cancer and Cancer Mortality > RESULTS
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In the paper
“Baseline telomere length was substantially shorter in participants with incident cancer (mean telomere length, 1.12; 95% CI, 1.01-1.23)than in those who remained free of cancer (mean telomere length, 1.53 [95% CI, 1.47-1.59];P Ͻ .001).”
§ Telomere Length and Risk of Incident Cancer and Cancer Mortality > RESULTS
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- It may state two separate claims as one. 15
- The quote only partly states this claim. 1
- Probably not a substantial claim. 9
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A total of 92 of 787 participants (11.7%) developed cancer (incidence rate, 13.3 per 1000 person-years).”
§ Telomere Length and Risk of Incident Cancer and Cancer Mortality > Abstract
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one. The quote only partly states this claim.
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In the paper
“in 44 of whom it was fatal (mortality rate, 6.2 per 1000 person-years; 95% CI, 4.6-8.3).”
§ Telomere Length and Risk of Incident Cancer and Cancer Mortality > RESULTS
Strength:plain· not yet calibratedn = 92Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In absolute terms 2, 14, and 28 of individuals in the longest, middle, and short-est telomere length groups, respectively, died of cancer, corresponding to mortality rates of 0.8, 6.0, and 12.9 per 1000 person-years, respectively.”
§ Telomere Length and Risk of Incident Cancer and Cancer Mortality > RESULTS
Strength:plain· not yet calibratedn = 28Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, an analysis revealed telomere length to have a similar predictive value for cancer in both men and women and in various age groups (FIGURE 3).”
- Also stated in: § Abstract · boosted
“The association equally applied to men and women and emerged as robust under a variety of circumstances.”
§ Telomere Length and Risk of Incident Cancer and Cancer Mortality > RESULTS
Strength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Abstract · boosted
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In the paper
“the overall number of cases is limited to 92 and 44, respectively”
§ Telomere Length and Risk of Incident Cancer and Cancer Mortality > COMMENT
Strength:plain· not yet calibratedn = 92Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Sensitivity analyses excluding participants with prior cancer or extending the list of covariates yielded similar results (Figure 1).”
§ Telomere Length and Risk of Incident Cancer and Cancer Mortality > RESULTS
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In the paper
“ConclusionIn this study population, there was a statistically significant inverse relationship between telomere length and both cancer incidence and mortality.”
- Also stated in: § COMMENT · boosted
“We demonstrated significant inverse correlations between baseline leukocyte telomerelengthandbothcancerincidenceand mortality,whichemergedasindependent of standard cancer risk factors (Figure 1).”
§ Telomere Length and Risk of Incident Cancer and Cancer Mortality > Abstract
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- Also stated in: § COMMENT · boosted
None of the sources cited for this claim have been checked yet.
In the paper
“In fibroblast cultures, accruing senescent cells were shown to produce and release high amounts of growth factors, 27 causing an overwhelming proliferation of the surrounding tissue, and to secrete metalloproteinase, diminishing intercellular adhesions and potentially favoring metastatic spread of tumors.28”
§ Telomere Length and Risk of Incident Cancer and Cancer Mortality > COMMENT
What the sources say
- Not checked yetcites [27]
- Not checked yetcites [28]
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Current evidence mainly derives from case-control studies and is inconsistent for various specific types of cancer.[7][8][9][10][11][12][13][14][15]”
§ Telomere Length and Risk of Incident Cancer and Cancer Mortality > ELOMERES ARE NUCLEOPROTEIN
What the sources say
- Not checked yetcites [7][8][9][10][11][12][13][14][15]
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Inamousemodel,deficiencyofthetelom-eraseRNAcomponent(theRNAtemplate fortelomereprolongation)causedamarkedlyenhancedfrequencyofchromosomal abnormalities and sporadic cancer, 2 particularly in the case of simultaneous inactivation of the tumor suppressor gene p53. 1”
§ Telomere Length and Risk of Incident Cancer and Cancer Mortality > COMMENT
What the sources say
- Not checked yetcites [2]
- Not checked yetcites [1]
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Dyskeratosis congenita, a rare disorder of telomere maintenance, was associated with visceral malignancies and squamous cell carcinoma of the skin. 32”
§ Telomere Length and Risk of Incident Cancer and Cancer Mortality > COMMENT
What the sources say
- Not checked yetcites [32]
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Moreover, a significantly higher productionofvascularendothelialgrowthfactor in senescent cells 29,30 may stimulate tumorgrowthanddisseminationbypromoting neovascularization.”
§ Telomere Length and Risk of Incident Cancer and Cancer Mortality > COMMENT
What the sources say
- Not checked yetcites [29]
- Not checked yetcites [30]
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“there are several lines of evidence from experimental animals, basic research, genome-wide association studies, and rare disorders of telomere maintenance [1][2][3][4][5] suggesting that short telomeres and concurrent chromosomal instability contribute to malignant cell transformation.3,6”
§ Telomere Length and Risk of Incident Cancer and Cancer Mortality > ELOMERES ARE NUCLEOPROTEIN
What the sources say
- Not checked yetcites [1][2][3][4][5]
- Not checked yetcites [3]
- Not checked yetcites [6]
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In conclusion, our study shows that short telomeres are associated with an enhanced risk of cancer and fatal cancer in particular.”
§ Telomere Length and Risk of Incident Cancer and Cancer Mortality > COMMENT
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In the paper
“Complete follow-up data on clinical end points occurring between 1995 and 2005 were available for the remaining 787 participants.”
§ Telomere Length and Risk of Incident Cancer and Cancer Mortality > METHODS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
In the paper
“Rafnar et al 5 demonstrated that polymorphisms in the gene encoding TERT, the catalytic subunit of telomerase, were associated with an increased risk for cancer of the lung, urinary bladder, prostate, and cervix.”
§ Telomere Length and Risk of Incident Cancer and Cancer Mortality > COMMENT
What the sources say
- Not checked yetcites Rafnar et al 5
Strength:boosted· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Population characteristics are comparable with those of other Western communities, but transferability of our findings to geographical regions with a prominently distinct genetic background remains to be established.”
§ Telomere Length and Risk of Incident Cancer and Cancer Mortality > COMMENT
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Our results corroborate well with previous evaluations demonstrating a link between short telomere length and bladder cancer, 7,8,22 renal cell carcinoma, 8,9 non-Hodgkin lymphoma, 10 lung cancer, 11 and head and neck tumors, 8 but failed to obtain significant correlations between short telomere length and colorectal and breast cancer.[12][13][14]23”
§ Telomere Length and Risk of Incident Cancer and Cancer Mortality > COMMENT
What the sources say
- Not checked yetcites [7]
- Not checked yetcites [8]
- Not checked yetcites [22]
- Not checked yetcites [9]
- Not checked yetcites [10]
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“As shown previously, 21 telomere length measurement by quantitative PCR was highly reproducible and correlated with Southern Blot-based mean telomere length restriction fragments.”
§ Telomere Length and Risk of Incident Cancer and Cancer Mortality > METHODS
What the sources say
- Not checked yetcites [21]
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Telomere length measurement was performed in quadruplicate, showed a high level of reproducibility, and was corrected for quantitative PCR efficiency.”
§ Telomere Length and Risk of Incident Cancer and Cancer Mortality > COMMENT
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
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.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“In several studies, not only did baseline LTL correlate with medical illnesses cross-sectionally but predicted the subsequent development of cancers, CVD, diabetes or mortality (Cawthon et al., 2003; Willeit et al 2010; Zhao et al., 2014).”
From Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging (2015) · cites this paper as Willeit et al 2010
In the citing paper
“Short telomeres have been linked to numerous diseases of aging and in many but not all cases, to all-cause and disease-specific mortality (12–17).”
From Determinants of telomere attrition over 1 year in healthy older women: stress and health behaviors matter (2015) · cites this paper as [14]
Citations
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Stegemann, C., Pechlaner, R., Willeit, P., Langley, S. R., Mangino, M., Mayr, U., Menni, C., Moayyeri, A., Santer, P., Rungger, G., et al. (2014) · Circulation · doi:10.1161/circulationaha.113.002500 · Cited by 570
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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
- Publisher
- American Medical Association (AMA)
- 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
- bronze
- doi.org
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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