ArticleTropical medicine and health2025
Telomere length promotes colorectal cancer through dual parallel pathways involving growth signaling and protein metabolism.
Article in Tropical medicine and health, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Mendelian randomization of risk factors for premenstrual disorders.Npj mental health research · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWhile telomeres traditionally protect against cancer through genomic stability, recent evidence suggests a paradoxical association with increased malignancy risk. This study employed comprehensive Mendelian randomization (MR) to investigate the causal relationship between telomere length (TL) and colorectal cancer (CRC) risk and elucidate the underlying biological mechanisms through systematic mediation analysis.
methodsWe performed two-sample MR using genetic instruments from large-scale genome-wide association studies (GWASs). CRC data were obtained from FinnGen R12 (discovery cohort: 11,790 cases and 378,749 controls) and the GWAS Catalog (replication cohort: 19,948 cases and 12,124 controls). The inverse-variance weighted method served as the primary analysis, complemented by MR‒Egger, weighted median, and MR-PRESSO sensitivity analyses. The multivariable MR was adjusted for body mass index (BMI), processed meat intake, inflammatory bowel disease (IBD), and colorectal polyps. Two-step mediation analysis investigated 35 blood and urine biomarkers as potential mediators, with colocalization analysis performed to distinguish linkage from pleiotropy.
resultsGenetically predicted longer telomeres were consistently positively associated with increased CRC risk across both cohorts (discovery: odds ratio [OR] = 1.282, 95% confidence interval [CI] 1.126-1.459, P < 0.001; replication: OR = 1.253, 95% CI 1.067-1.472, P = 0.006). This association remained robust across multiple analytical methods and was independent of BMI, processed meat intake, IBD, and colorectal polyps. Mediation analysis revealed three significant mediators representing dual parallel mechanisms: insulin-like growth factor-1 (IGF-1) mediated 4.2% of the total effect through enhanced growth signaling (P = 0.0265), whereas total protein (TP) and nonalbumin protein (NAP) collectively mediated 19.67% through compromised protein homeostasis (10.33% and 9.34%, respectively; both P < 0.005). Colocalization analysis revealed the shared genetic architecture underlying these associations.
conclusionsLonger telomeres causally increase CRC risk through dual parallel pathways: enhanced cellular proliferation via IGF-1 signaling and compromised immune surveillance through protein metabolic dysfunction. These findings challenge conventional protective roles attributed to telomeres and suggest that individuals with genetically longer telomeres may benefit from enhanced screening protocols and targeted interventions addressing both growth factor signaling and protein metabolic homeostasis.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.