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

Abstract

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.

Lifetime posttraumatic stress disorder as a predictor of mortality: a systematic review and meta-analysis

“…The characteristics of the 30 included studies [ 22 , 23 , 36 – 63 ], encompassing at least 2.1 million participants with a confirmed or probable diagnosis of PTSD are shown in Table 1 . All studies were cohort studies, except for one case-control [ 56 ].…”

“…The majority of the included studies focused specifically on veteran military populations, and only 12 studies analysed civilian populations. Of the civilian studies, two involved participants exposed to war trauma [ 38 , 49 ], two terrorist attacks [ 41 , 51 ], one a natural disaster [ 44 ], and seven included participants exposed to any type of trauma [ 22 , 23 , 45 , 58 – 61 ].…”

“…All but seven studies [ 22 , 23 , 37 , 51 , 56 , 58 , 62 ] investigated all-cause mortality. While we have excluded studies that focused specifically on suicide, four studies [ 36 , 48 , 60 , 62 ] reported findings for all external causes of death (which included suicide, homicide and accidental deaths).…”

“…While we have excluded studies that focused specifically on suicide, four studies [ 36 , 48 , 60 , 62 ] reported findings for all external causes of death (which included suicide, homicide and accidental deaths). Four studies analysed CVD-related deaths [ 23 , 36 , 41 , 55 ], three studies reported deaths by cancer [ 22 , 36 , 48 ], and one study investigated infection-related deaths [ 58 ].…”

“…Amongst the studies that measured symptoms or severity of PTSD, two (which presented null findings) were based on a dimensional metric [ 52 , 54 ] (rather than a 0 vs. 1 determination to indicate probable PTSD diagnosis), and were excluded from analyses. An additional article was also excluded from the main meta-analyses [ 22 ] as it utilised the same participants as another study [ 61 ], but was later included in the subgroup analyses investigating causes of death.…”