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Background Ovarian cancer risk in adulthood may be affected by early life exposure to tobacco smoke. We investigated this relationship in two large prospective cohorts, the Nurses’ Health Study (NHS) and NHSII. Methods In total, analyses included 110 305 NHS participants (1976–2016) and 112 859 NHSII participants (1989–2017). Self-reported early life smoking exposures were queried at baseline or follow-up questionnaires. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of ovarian cancer overall and by tumour histotype. Results Overall, ovarian cancer risk was not different among participants whose mothers did versus did not smoke during pregnancy (HR = 1.05, 95% CI: 0.87–1.27); however, an increased risk was observed among women who themselves were never smokers (HR = 1.38, 95% CI: 1.05–1.81) but not among ever smokers (HR = 0.86, 95% CI: 0.66–1.14; Pheterogeneity = 0.02). Compared with women who never smoked, ovarian cancer risk was similar for women who started to smoke at age &amp;lt;18 (HR = 0.98, 95% CI: 0.86–1.11) or ≥18 (HR = 1.02, 95% CI: 0.93–1.12). These associations did not differ by histotype (Pheterogeneity ≥0.35). Parental smoking in the home during childhood/adolescence was related to a 15% increased risk of ovarian cancer in adulthood (HR = 1.15, 95% CI: 1.04–1.27) and this association was suggestively stronger among women with non-serous/low-grade serous tumours (HR = 1.28, 95% CI: 1.02–1.61) versus high-grade serous/poorly differentiated tumours (HR = 1.09, 95% CI: 0.93–1.28; Pheterogeneity = 0.25). Conclusions Exposure to parental tobacco smoke in the home, but not early initiation of smoking, was associated with a modest elevated risk of ovarian cancer. Further investigations are required to confirm these findings and elucidate underlying mechanisms.

Early life exposure to tobacco smoke and ovarian cancer risk in adulthood