Sleep Reduction and Depressive Symptoms Synergistically Increase Cancer Risk in Middle-Aged and Older Chinese Adults: Evidence from the CHARLS Cohort

Background The independent and joint effects of sleep reduction and depression on cancer risk remain understudied in Chinese populations, particularly regarding synergistic mechanisms. This study aims to examine the impact of sleep reduction (≤ 6 hours) and depressive symptoms on cancer incidence among middle-aged and older adults in China. We will analyze both the independent and combined effects of these two factors, in order to provide important insights for understanding cancer etiology and informing prevention strategies. Methods The study utilized robust longitudinal data (2011–2020) from 14,349 cancer-free adults aged ≥ 45 years in the China Health and Retirement Longitudinal Study (CHARLS). We meticulously examined associations between baseline sleep duration (≤ 6h vs. >6h), depressive symptoms (CESD- 10 < 10 was defined as no depressive symptoms, 10 ≤ CESD- 10 <15 was classified as mild depressive symptoms, and CESD-10 ≥ 15 was classified as moderate to severe depressive symptoms.), and incident cancer. Our Cox models quantified hazard ratios (HRs) adjusted for sociodemographic, behavioural, and clinical confounders. We also performed additive interaction (RERI/AP/S) and mediation analyses, ensuring a comprehensive understanding of the data. Results Over 96.7 ± 23.88 months, 418 cancer cases occurred. Sleep reduction (≤ 6h) independently increased cancer risk by 33% (adjusted HR = 1.33, 95% CI:1.03–1.73), while moderate-severe depression increased risk by 49% (HR = 1.49, 1.08–2.07). When these two factors coexisted, they demonstrated synergistic effects, meaning their combined impact was greater than the sum of their individual effects: the combined risk was 59% higher (HR = 1.59, 1.13–2.22) with significant additive interaction (RERI = 0.34, 95% CI:0.05–0.63; AP = 21.4%, 0.03–0.39). Depression mediated only 16.5% (95% CI: -22.7-97.4) of the sleep-cancer association. Subgroups at highest risk included females, adults < 60 years, and those without hypertension/diabetes. Conclusion Sleep reduction and depression (especially moderate to severe depression) independently increase cancer risk in middle-aged/older Chinese adults, with significant synergistic effects when coexisting. Limited mediation by depression suggests distinct biological pathways. Integrated sleep-mental health interventions may enhance cancer prevention.