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.