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Short telomere length linked to reduced survival after cancer
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Patients with the shortest telomere length were more likely to die of cancer than those with longer telomeres, according to results of a prospective study.
An international group of researchers tested the hypotheses that short telomere length was associated with increases in cancer risk and early mortality. The study cohort included 47,102 people from Denmark who participated in the Copenhagen City Heart Study and the Copenhagen General Population Study.
The investigators measured leukocyte telomere length and followed patients for up to 20 years.
A linear decrease in telomere length occurred as participants grew older (P<.001).
Researchers reported 3,142 first cancers in the cohort during follow-up, and there were 1,730 deaths among these participants.
Researchers observed a link between decreasing quartile of telomere length and decreasing survival after cancer (log-rank P<.001).
Multivariate analysis results indicated that early mortality carried an HR of 1.31 (95% CI, 1.14-1.52) among those in the quartile with the shortest telomere length vs. the longest. Those in the lowest decile of telomere length had an HR for early death of 1.43 (95% CI, 1.13-1.80) compared with those in the highest decile.
For cancer risk, the unadjusted HR among those in the lowest quartile of telomere length vs. longest was 1.74 (95% CI, 1.58-1.93). The lowest decile of telomere length carried an HR for cancer risk of 2.00 (95% CI, 1.70-2.35) compared with the highest decile. Multivariate adjustment changed these HRs to 0.98 (95% CI, 0.88-1.08) for the lowest quartile vs. highest and 0.95 (95% CI, 0.80-1.11) for lowest decile vs. highest.
“Short telomere length is associated with reduced survival after cancer but not with cancer risk,” the researchers concluded.
Association studies of telomere lengths and cancer likely have been influenced by methodological issues, such as lack of interlaboratory comparisons of telomere length measurements, reverse causation bias, and limited reporting of DNA extraction and handling methods, Sharon A. Savage, MD, FAAP, Shahinaz M. Gadalla, MD, PhD, and Stephen J. Chanock, MD, all of the division of cancer epidemiology and genetics at NCI, wrote in an accompanying editorial.
“Because therapeutic interventions can affect telomere lengths, it will be important to integrate clinical data in future studies,” they wrote. “If telomere lengths are to be used as effective biomarkers for cancer prevention or intervention, it will be necessary to more thoroughly understand the connection between telomere biology, cancer, chronic disease and mortality in the general population.”
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