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.

先前的研究表明心理压力对癌症发展的潜在作用，而家庭因素在这种关联中的作用尚未得到充分探索。我们进行了一项全国性队列研究，包括 167,836 名于 1981 年至 2016 年间在瑞典被诊断为首发压力相关疾病（包括创伤后压力障碍、急性压力反应、适应障碍和其他压力反应）的个体（即暴露患者） 、1,631,801 名出生年份和性别匹配的未暴露个体，以及 179,209 名未受影响的暴露患者的兄弟姐妹。Cox 模型用于估计新诊断的癌症和癌症相关死亡的风险比 (HR)，在诊断出压力相关疾病后超过 1 年。我们进一步研究了行为相关疾病在压力相关疾病与吸烟或酒精相关癌症发病率和死亡率之间的潜在中介作用。我们发现，与匹配的未暴露个体相比，暴露患者的癌症发病率和死亡率风险适度升高（发生率：HR = 1.03，95% CI 1.01-1.06；死亡率：HR = 1.13，95% CI 1.07-1.18），而在比较时则没有全兄弟姐妹（发生率：HR = 1.03, 95% CI 0.99-1.08；死亡率：HR = 1.09, 95% CI 1.00-1.19）。同样，在基于人群的比较中，建议的个别癌症部位（或组）的发病率和死亡率升高在兄弟姐妹间比较中趋于零。在基于人群的比较中吸烟或酒精相关癌症的风险升高（发生率：HR = 1.18, 95% CI 1. 11–1.24；死亡率：HR = 1.20, 95% CI 1.12–1.29）部分由随访期间的酒精相关发病率介导。总的来说，我们的研究结果表明，压力相关疾病与癌症风险和死亡率之间的关联在很大程度上可以通过家庭因素来解释，包括共同的行为危害。