Joint effects of sleep and PRS on thyroid cancer risk: a cohort study from the UK Biobank

Background Sleep disturbance and obesity are linked to thyroid cancer (TC) risk, while genetic factors may modify these associations. We explored how genetic predisposition and obesity influence sleep–TC risk.Methods This prospective UK Biobank cohort included 502,505 adults. Sleep metrics were self-reported, and TC cases were identified via ICD codes (C73/193) and self-report. Polygenic risk scores (PRS) were derived for 356,451 European participants.Results Over 10.38 years, 471 TC cases (341 female) emerged among 388,006 participants. Sleep duration showed a linear association with TC risk (P<0.001). Unfavorable sleep factors increased TC risk (HR=1.32, 95%CI 1.06-1.65), with long sleep conferring HR=1.43 (1.06-1.92), particularly in females. Combined unfavorable sleep and high PRS had the highest risk (HR=4.48, 2.74-7.34). Compared to normal sleep and waist-hip ratio (WHR), long sleep with high WHR showed HR=1.74 (1.04-2.92). WHR mediated 3.30% and 17.00% of the associations for unfavorable sleep and long sleep, respectively.Conclusion Long sleep duration had detrimental effects on TC risk, particularly in females. Joint effects of longer sleep duration with higher WHR and PRS were found on TC risk. Our results highlight the importance of favorable sleep factors for TC prevention, especially in participants with higher TC-PRS and WHR.