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Telomere Length May Predict Cancer Risk
  MedPage Today
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* Explain to interested patients that this observational study could not prove a causal relationship between shorter telomeres and elevated cancer risk.
The length of a person's telomeres is inversely associated with the risk of getting -- and dying from -- cancer, researchers found.
Compared with individuals with the longest telomeres, those with the shortest were three times as likely to develop cancer over a 10-year period (HR 3.11, 95% CI 1.65 to 5.84), according to Stefan Kiechl, MD, of Innsbruck Medical University in Austria, and colleagues.
Those with the shortest telomeres were also 11 times more likely to die from cancer (HR 11.11, 95% CI 2.61 to 47.36), the researchers reported in the July 7 issue of the Journal of the American Medical Association.
"It is appealing to assume that the association between short leukocyte telomere length and cancer formation is partially mediated by the aging of the immune system itself," Kiechl and his colleagues wrote. "Aging of leukocytes reflected by short telomere length may impair immune surveillance and reduce the clearance of tumor cells."
Another possible explanation for the association, though, is that "cells with a critically short telomere length may under certain circumstances reactivate the enzyme telomerase to escape from cell senescence and thereby facilitate malignant transformation," they wrote.
Telomeres cap the ends of chromosomes, and shorten as people age. Critically short telomeres can lead to chromosomal instability
Whether this instability was associated with cancer risk has not been well studied in epidemiological analyses, with most evidence of such a relationship coming from case-control studies.
Kiechl and his colleagues explored the issue with the prospective, population-based Bruneck Study in Italy.
The current analysis included 787 individuals ages 40 to 79 who were free from cancer at baseline in 1995 and were followed to 2005. Telomere length in peripheral blood leukocytes was measured at baseline.
During follow-up, 11.7% developed cancer, excluding nonmelanoma skin cancer.
Mean telomere length was significantly shorter in the participants with cancer (P<0.001).
After adjustment for several standard cancer risk factors, shorter telomere length at baseline was associated with an increased risk of developing cancer (HR per one standard-deviation decrease in loge-transformed telomere length 1.60, 95% CI 1.30 to 1.98).
That increase in risk equates to about a 12.8-year difference in chronological age, according to the researchers.
Although participants with the shortest telomeres had the greatest increase in cancer risk, those in the middle tertile of telomere length had more than double the risk of those with the longest telomeres (HR 2.15, 95% CI 1.12 to 4.14).
The rates of cancer according to decreasing tertile of telomere length were 5.1, 14.2, and 22.5 per 1,000 person-years.
The association between telomere length and cancer risk was consistent across patient subgroups.
The number of cancer cases was too small to create meaningful analyses of individual cancer types, but shorter telomeres appeared to be preferentially associated with more deadly malignancies, such as gastric, lung, and ovarian cancers.
Of the participants who developed cancer, nearly half (47.8%) died from it.
Cancer mortality was also associated with shorter telomere length (HR per one standard-deviation decrease in loge-transformed telomere length 2.13, 95% CI 1.58 to 2.86).
The researchers acknowledged some limitations of the study, including the limited generalizability of the findings to nonwhite individuals and people living in other geographical areas. Also, telomere length was measured in circulating blood leukocytes only rather than in a variety of tissues.
The study was supported by the Pustertaler Verein zur Pravention von Herz und Hirngefaesserkrankungen, Gesundheitsbezirk Bruneck, and the Assessorat fuer Gesundheit, Province of Bolzano, Italy. The lead author was supported by a scholarship from the Dr. Johannes and Hertha Tuba Foundation. Another study author was supported by a grant from the Competence Centers for Excellent Technologies Center, ONCOTYROL, and the Integriertes Forschungs und Therapiezentrum of Innsbruck Medical University.
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