Parity and Age at First Birth in Relation to Female Cancer Risk: A Systematic Review and Dose-Response Meta-Analysis

Background Fertility decline and delayed childbearing may influence women’s long-term cancer risk. Objectives To quantify associations of parous status, parity and age at first birth with incident female cancers and assess dose-response/non-linearity. Search strategy PubMed and Embase were searched from inception to 18 Nov 2024. Selection criteria Cohort and case–control studies in adult women reporting parous status, parity or age at first birth in relation to incident cancer. Data collection and analysis Cancers were harmonized using WHO Global Health Estimates 2021. Random-effects meta-analysis and prespecified linear/quadratic/spline dose–response models were used with AIC-guided selection. Main results We included 123 studies (~18.75 million women) across 17 cancer sites and seven tumors’ subtypes. Ever-parous versus nulliparous women had lower breast cancer risk (ES 0.79, 95% CI 0.67–0.91). Each additional birth was associated with lower risks of breast (7% per birth), ovarian (14%), endometrial (29%) and lung cancers (21%). Each one-year increase in age at first birth was associated with higher risks of breast cancer (3% per year) and melanoma/skin cancer (2.5% per year). U-shaped associations were observed for endometrial and thyroid cancers. Subtype analyses suggested reduced epithelial ovarian cancer risk and increased triple-negative breast cancer risk among parous women. Conclusions Reproductive history shows heterogeneous, site- and subtype-specific associations with cancer risk; parity appears protective for several cancers, whereas delayed childbearing may increase breast and skin cancer risk.