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JAMA. 2010 Jul 7;304(1):69-75. doi: 10.1001/jama.2010.897.

Telomere length and risk of incident cancer and cancer mortality.

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  • 1Department of Neurology, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria.

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.

PMID:
20606151
[PubMed - indexed for MEDLINE]
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