Stress-related disorders and subsequent cancer risk and mortality : a population-based and sibling-controlled cohort study in Sweden

Funding Information: This research was supported by the Swedish Research Council through the Swedish Initiative for research on Microdata in the Social and Medical Sciences (SIMSAM) framework. Funding Information: This work was supported by Swedish Cancer Society (20 0846 PjF to F. Fang), 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (ZYYC21005 to H. Song), and the National Natural Science Foundation of China (81971262 to H. Song). Publisher Copyright: © 2022, The Author(s).Prior research has suggested a potential role of psychological stress on cancer development while the role of familial factors on this association is underexplored. We conducted a nationwide cohort study including 167,836 individuals with a first-onset stress-related disorder (including post-traumatic stress disorder, acute stress reaction, adjustment disorder and other stress reactions) diagnosed between 1981 and 2016 in Sweden (i.e., exposed patients), 1,631,801 birth year- and sex-matched unexposed individuals, and 179,209 unaffected full siblings of the exposed patients. Cox models were used to estimate the hazard ratios (HRs) of newly diagnosed cancer and cancer-related death, beyond 1 year after diagnosis of stress-related disorders. We further examined the potential mediation roles of behavior-related morbidities in the associations of stress-related disorders with smoking or alcohol-related cancer incidence and mortality. We found modestly elevated risks of cancer incidence and mortality among exposed patients compared with matched unexposed individuals (incidence: HR = 1.03, 95% CI 1.01–1.06; mortality: HR = 1.13, 95% CI 1.07–1.18), while not when comparing with full siblings (incidence: HR = 1.03, 95% CI 0.99–1.08; mortality: HR = 1.09, 95% CI 1.00-1.19). Similarly, the suggested elevations in incidence and mortality of individual cancer sites (or groups) in the population-based comparison attenuated towards null in the between-sibling comparison. The risk elevations for smoking or alcohol-related cancers in the population-based comparison (incidence: HR = 1.18, 95% CI 1.11–1.24; mortality: HR = 1.20, 95% CI 1.12–1.29) were partially mediated by alcohol-related morbidities during follow-up. Collectively, our findings suggest that the association between stress-related disorders and cancer risk and mortality is largely explained by familial factors, including shared behavioral hazards.Peer reviewe