Burden of early-onset pancreatic cancer and its association with risk factors in women of childbearing age

INTRODUCTION: Early-onset pancreatic cancer (EOPC), diagnosed before age 50, is rising globally. Women of childbearing age (WCBA, 15-49 years) constitute nearly the same population as EOPC patients but have unique metabolic vulnerabilities. The intersection of EOPC trends with WCBA-specific metabolic risks remains underexplored. This study delineates the global EOPC burden among WCBA and its links to core metabolic determinants, providing an evidence base to guide targeted interventions in this priority population and support progress toward international development goals. METHODS: A two-stage design was employed. First, Global Burden of Disease 2023 data were analyzed to assess EOPC mortality and disability-adjusted life years (DALYs) among WCBA (1990-2023), quantifying trends and population attributable fractions (PAFs) for high fasting blood glucose (FBG) and high body mass index (BMI). Second, a retrospective case-control study provided supportive clinical correlation for the identified risk factors. RESULTS: Globally, absolute EOPC deaths and DALYs in WCBA more than doubled from 1990 to 2023. Age-standardized rates remained stable globally, but increased in low and middle Sociodemographic Index (SDI) regions. High FBG was the largest population-attributable risk factor (global PAF = approximately 64%), with an inverse SDI gradient. High BMI PAF showed an inverted U-shaped distribution. In the supportive clinical analysis, high FBG remained independently associated with EOPC (adjusted OR=4.64; 95% CI: 2.88-7.49), while high BMI lost significance after adjustment, suggesting overlapping metabolic pathways. CONCLUSION: Demographic factors (population growth and aging) drive most of the increase in absolute EOPC burden among WCBA. High FBG is the leading modifiable risk factor at the population level, though reverse causation may partly explain its strong association. Targeted glycemic control and metabolic interventions are urgently needed in this population.