Increased risk of young-onset ovarian cancer in women with non-alcoholic fatty liver disease: A nationwide cohort study of 2.3 million women aged 20-39 years.

Little is known about modifiable risk factors for young-onset ovarian cancer, except for obesity and nulliparity. We investigated the association between non-alcoholic fatty liver disease (NAFLD) and the risk of young-onset ovarian cancer. A total of 2,376,482 women aged 20-39 years who underwent national health screening under the Korean National Health Insurance Service between 2009 and 2012 were included in this nationwide cohort study and followed-up until December 2022. The fatty liver index was used as a diagnostic biomarker for NAFLD. The risk was estimated using multivariable Cox proportional hazards models after adjusting for potential confounders. During 26.8 million person-years of follow-up (median: 11.5 years), 6,319 young women were newly diagnosed with young-onset ovarian cancer. The cumulative incidence probability was significantly higher for those with NAFLD than for those without (log-rank P < 0.01). NAFLD was associated with an increased risk of young-onset ovarian cancer (adjusted hazard ratio [aHR], 95% confidence interval [CI]: 1.30, 1.16-1.45). As the severity of NAFLD increased, the risk of young-onset ovarian cancer tended to increase (aHR, 95% CI: Moderate and severe NAFLD; 1.26, 1.12-1.41 and 1.45, 1.22-1.72, respectively; P for trend < 0.01). NAFLD was independently associated with an increased risk of young-onset ovarian cancer. As NAFLD is modifiable, our findings may benefit the next generation by reducing premature morbidity and mortality associated with young-onset ovarian cancer.