Global Burden of Ovarian Cancer and Causal Risk Factors from 1990 to 2021: An Integrated GBD and Mendelian Randomization Analysis.
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BACKGROUND: Ovarian cancer seriously threatens women's health due to its poor prognosis. This study integrates Global Burden of Disease (GBD) and Mendelian randomization analyses, to evaluate the global burden of ovarian cancer and identify causal risk factors using large-scale GWAS summary statistics for 12 exposures. METHODS: We utilized statistics from the GBD 2021 study to analyze global trends in ovarian cancer across 204 countries and territories from 1990 to 2021, along with all risk factors, high BMI and occupational exposure to asbestos, and generated forecasts for the subsequent decade. Furthermore, we employed a range of statistical genetics methods to analyze data from the genome-wide association studies, to comprehensively assess the causal relationships between variable risk factors and ovarian cancer at the individual level. RESULTS: For all risk factors, the mortality and disability-adjusted life years (DALYs) numbers rose from 1990 to 2021 globally, while the age-standardized DALY rate (ASDR) and age-standardized mortality rate (ASMR) showed a decreasing inclination. Attributable to occupational exposure to asbestos, the mortality and DALYs numbers showed an increasing trend, while the ASMR and ASDR showed a decreasing trend. For high BMI, mortality, DALYs number, the ASMR and ASDR all demonstrated an uptrend. The projection to next decade shows a similar trend. Based on MR analyses, we forecasted that the HIP, visceral adiposity, waist circumference, alcohol intake frequency, childhood BMI, HIPadjBMI, and lifetime smoking were positively associated with ovarian cancer (HIP: OR=1.29, 95% CI: 1.13-1.48; visceral adiposity: OR=1.22, 95% CI: 1.07, 1.38, waist circumference: OR=1.28, 95% CI: 1.10-1.48). Alcohol use disorder, dried fruit intake, education, fresh fruit intake and magnesium were negatively associated with ovarian cancer (alcohol use disorder: OR=0.91, 95% CI: 0.83-0.99). CONCLUSION: Our research presents a detailed analysis of the overall health burden imposed by ovarian cancer. Furthermore, the findings suggest that adiposity, alcohol intake frequency and smoking may serve as significant indicators of an elevated risk of ovarian cancer. These insights are expected to assist policymakers in enhancing the implementation of prevention strategies.