Are long telomeres better than short? Relative contributions of genetically predicted telomere length to neoplastic and non-neoplastic disease risk and population health burden.
Level 3 - non-randomized controlled study
Population health modeling and risk projection using summary data from Mendelian randomization meta-analysis and registries (design analogy)
PubMed 33031470 · doi:10.1371/journal.pone.0240185
What was done
The authors modeled the population-level disease incidence and burden associated with genetically determined leukocyte telomere length (gTL). Disease odds ratios from a published Mendelian randomization (MR) meta-analysis were combined with incidence and Disability-Adjusted Life Years (DALY) data from the Institute for Health Metrics and Evaluation (IHME) and SEER cancer records for a European population. They calculated the excess incidence and DALYs per 100,000 persons per standard deviation (SD) change in gTL across 9 cancers associated with long gTL and 4 degenerative diseases associated with short gTL.
What was found
Long gTL was associated with an excess incidence of 94.04 cases per 100,000 persons per SD (95% CI: 45.49 to 168.84) across 9 cancers, while short gTL was associated with an excess incidence of 121.49 cases per 100,000 persons per SD (95% CI: 48.40 to 228.58) across 4 non-neoplastic diseases. In terms of overall population disease burden, long gTL contributed an excess 1,255.25 DALYs per 100,000 persons per SD (95% CI: 662.71 to 2,163.83) due to cancer, compared to an excess 1,007.75 DALYs per 100,000 persons per SD (95% CI: 411.63 to 1,847.34) from degenerative conditions.
Why it matters
This paper quantitatively supports the cancer-aging trade-off, showing that while long telomeres carry higher relative risks for specific cancers, the higher baseline population incidence of degenerative diseases balances the net disease burden of short telomeres.
Limits
The study is a mathematical projection based on aggregated summary-level data rather than individual longitudinal follow-up. The analysis is limited to a European population and only includes the 9 cancers and 4 non-neoplastic diseases established in prior MR studies. The total underlying sample size across registries and MR studies is not reported in the abstract.
Cited by
- supports Telomere length exhibits a U-shaped relationship with health risks, where having telomeres that are either excessively short or excessively long is disadvantageous.