Swedish matched-cohort on the association between maternal polyendocrine metabolic ovarian syndrome and next-generation cancer-risk.
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BACKGROUND: Polyendocrine metabolic ovarian syndrome (PMOS) is an endocrine and metabolic disorder associated with adverse perinatal and long-term health outcomes, yet its impact on cancer risk in children remains unclear. METHODS: We conducted a nationwide, register-based matched cohort study in Sweden, including children of primiparous women with (N = 22,955) and without PMOS (N = 103,613) born between 1973 and 2018. Children were followed from birth until cancer diagnosis, death, or December 2018. Conditional Cox proportional hazards models estimated the adjusted hazard ratio (aHR) with 95% confidence interval (CI), incorporating time-varying effects when the proportional hazards assumption was violated. RESULTS: During follow-up, 666 children were diagnosed with cancer. Compared with children born to women without PMOS, overall cancer risk among children of women with PMOS differed by sex and over time. Among sons, higher hazards at 1 year were observed (aHR 4.17; 95% CI: 2.51-6.93), decreasing by 10 years (aHR 1.53; 95% CI 1.08-2.18). In daughters, hazard ratios did not indicate a change in overall cancer risk compared to reference. When both sexes were combined, risk of lymphatic and hematopoietic malignancies was higher (aHR 2.43; 95% CI 1.36-4.33). Competing risks of death did not materially alter the associations. CONCLUSIONS: Overall cancer risk among children born to women with PMOS differed by sex and over time, with higher risks in sons during early life. These findings suggest that maternal PMOS may be associated with differential cancer susceptibility across the life course.