Cancer Epidemiology, Biomarkers & Prevention · Sep 30, 2020

Leukocyte Telomere Length and Bladder Cancer Risk: A Large Case-Control Study and Mendelian Randomization Analysis

By Chen M, Xu Y, Xu J et al.

BACKGROUND: Leukocyte telomere length (LTL) has been associated with risk of several cancers. The association between LTL and bladder cancer is still inconsistent. METHODS: In this large case-control study consisting of 2,011 patients with bladder cancer and 2,259 healthy controls of European ancestry, we investigated the associations of real-time qPCR-measured LTL (a retrospective case-control study) and genetically predicted LTL [a Mendelian randomization (MR) study] with bladder cancer risk. Genotypes from 10 LTL-associated SNPs were used as instrumental variables to predict LTL. We used an individual level data-based weighted genetic risk score (GRS) and a summary statistics-based inverse-variance weighting (IVW) method in MR analyses. RESULTS: The qPCR-measured LTL was shorter in cases with muscle-invasive bladder cancer (MIBC) than those with non-muscle-invasive bladder cancer [NMIBC; ratio of telomere repeats copy number to single gene copy number (T/S): 1.19 ± 0.34 vs. 1.23 ± 0.36, P = 0.081]. Multivariable logistic regression analyses showed long qPCR-measured LTL was associated with a reduced risk of MIBC. In MR analyses, genetically predicted LTL was weakly associated with bladder cancer risk in both the GRS analysis [OR = 1.13, per SD increase; 95% confidence interval (CI), 0.73-1.75; P = 0.595] and the IVW analysis (OR = 1.14 per SD increase; 95% CI, 0.75-1.74; P = 0.543). CONCLUSIONS: There was no strong evidence supporting an association between LTL and bladder cancer risk in European Americans. IMPACT: This is the largest study of LTL and bladder cancer risk. The study showed that LTL does not play an important role in bladder cancer etiology.

doi.org/10.1158/1055-9965.epi-20-0351PubMed 32998948Biomarkers