Leukocyte telomere length and bladder cancer risk: a large case control study and Mendelian randomization analysis
Menée à partir de données portant sur 2 011 patients atteints d'un cancer de la vessie et sur 2 259 témoins, cette étude analyse l'association entre la longueur des télomères leucocytaires et le risque de développer la maladie
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 bladder cancer patients and 2,259 healthy controls of European ancestry, we investigated the associations of real-time quantitative PCR (qPCR) measured LTL (a retrospective case control study) and genetically predicted LTL (a Mendelian randomization [MR] study) with bladder cancer risk. Genotypes from ten LTL-associated single nucleotide polymorphisms 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% 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.