Habitual napping and cancer incidence: a prospective study from the UK Biobank with metabolomic mediation analysis

Increased daytime napping frequency is potentially associated with elevated cancer risk. Further research is warranted to validate this association and elucidate the underlying biological mechanisms. Statement of Significance This study provides the comprehensive investigation of how daytime napping influence cancer risk through biological mechanisms. By analyzing data from 461 000 individuals in the UK Biobank, we demonstrated that increased daytime napping frequency is associated with elevated cancer risk, particularly for breast and esophageal cancers. Our research employed both observational and genetic approaches, using PRS to assess the contribution of genetic liability and to provide evidence which was less susceptible to traditional confounding. Through mediation analysis of 325 NMR metabolites, we identified lipid metabolic dysfunction as the key biological pathway linking napping to cancer development. Specifically, cholesterol composition in small low-density lipoproteins explained 13.3 per cent of this association. These findings provide the biological explanation for how daytime napping influences cancer development and highlight lipid metabolism as a potential intervention target for cancer prevention. Future studies are essential to validate this association and elucidate the underlying biological mechanisms.