Leukocyte Telomere Length and Bladder Cancer Risk: A Large Case–Control Study and Mendelian Randomization Analysis
| Autor: | Haidee Chancoco, Junfeng Xu, Yifan Xu, Jian Gu, Meng Chen |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Oncology medicine.medical_specialty Epidemiology Single-nucleotide polymorphism Real-Time Polymerase Chain Reaction Logistic regression Risk Assessment 03 medical and health sciences 0302 clinical medicine Internal medicine Genotype Mendelian randomization Leukocytes medicine Humans Genetic Predisposition to Disease Telomere Shortening Aged Bladder cancer business.industry Case-control study Mendelian Randomization Analysis Middle Aged medicine.disease Confidence interval 030104 developmental biology Urinary Bladder Neoplasms Case-Control Studies 030220 oncology & carcinogenesis Female business |
| Zdroj: | Cancer Epidemiology, Biomarkers & Prevention. 30:203-209 |
| ISSN: | 1538-7755 1055-9965 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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