Introduction

Evidence on the association between diabetes and risk of bladder cancer has been controversial. In addition, findings on the associations between duration of diabetes, diabetes treatment, and risk of bladder cancer have been inconsistent.

Methods

A total of 148,208 participants in Women's Health Initiative study were included. Information on diabetes status, diabetes duration, and treatment was collected both at baseline and during follow-up. Information on potential confounders including age, race/ethnicity, education, occupation, family history of cancer, smoking status, alcohol consumption, total physical activity, body mass index, and daily dietary intake were collected at baseline. Bladder cancer cases were collected and confirmed by a centralized review of pathology reports. Cox proportional hazard models with time-varying covariates were used to examine associations of diabetes status, duration of diabetes, and diabetes treatment with bladder cancer risk.

Results

During a median follow-up of 18.5 years, 865 bladder cancer cases were identified. There were no significant associations of diabetes, duration of diabetes, or diabetes treatment with risk of bladder cancer. Participants with prevalent diabetes did not have significantly higher risk of bladder cancer compared with those without diabetes.

Conclusion

Diabetes was not significantly associated with risk of bladder cancer among postmenopausal women.

Mitochondrial DNA (mtDNA) quality and quantity relate to two hallmarks of aging-genomic instability and mitochondrial dysfunction. Physical performance relies on mitochondrial integrity and declines with age, yet the interactions between mtDNA quantity, quality, and physical performance are unclear. Using a validated digital PCR assay specific for mtDNA deletions, we tested the hypothesis that skeletal muscle mtDNA deletion mutation frequency (i.e., a measure of mtDNA quality) or mtDNA copy number predicts physical performance in older adults. Total DNA was isolated from vastus lateralis muscle biopsies and used to quantitate mtDNA copy number and mtDNA deletion frequency by digital PCR. The biopsies were obtained from a cross-sectional cohort of 53 adults aged 50 to 86 years. Before the biopsy procedure, physical performance measurements were collected, including VO_2max, modified physical performance test score, 6-min walk distance, gait speed, grip strength, and total lean and leg mass. Linear regression models were used to evaluate the relationships between age, sex, and the outcomes. We found that mtDNA deletion mutation frequency increased exponentially with advancing age. On average from ages 50 to 86, deletion frequency increased from 0.008 to 0.15%, an 18-fold increase. Females may have lower deletion frequencies than males at older ages. We also measured declines in VO_2max and mtDNA copy number with age in both sexes. The mtDNA deletion frequency measured from single skeletal muscle biopsies predicted 13.3% of the variation in VO_2max. Copy number explained 22.6% of the variation in mtDNA deletion frequency and 10.4% of the lean mass variation. We found predictive relationships between age, mtDNA deletion mutation frequency, mtDNA copy number, and physical performance. These data are consistent with a role for mitochondrial function and genome integrity in maintaining physical performance with age. Analyses of mtDNA quality and quantity in larger cohorts and longitudinal studies could extend our understanding of the importance of mitochondrial DNA in human aging and longevity.