Background: Despite longstanding interest in the association between psychological stress and cancer risk, epidemiological evidence remains inconclusive. Prospective cohort studies investigating the effects of exposure to chronic stress have reported mixed results, including null, protective, and detrimental associations with cancer risk. Broad, domain-general measures of stress—such as exposure to multiple stressful life events or high perceived stress—capture the cumulative impact of stress arising from diverse sources. To date, no systematic review has comprehensively examined the relationship between cumulative stressful life events and perceived stress in adulthood and cancer risk.
Objectives: This study aimed to: (1) assess the quantity and methodological quality of prospective evidence linking psychological stress to cancer risk, and (2) quantify the association between stress (operationalized as stressful life events or perceived stress) and the incidence of overall and site-specific cancers through meta-analysis.
Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines (PROSPERO: IDCRD42020175681). We searched major databases for prospective studies evaluating the impact of stressful life events (SLE) or perceived stress (PS) on cancer incidence. Methodological quality was assessed using the NIH Tool for Observational Studies, and the certainty of evidence was graded using the GRADE framework. Hazard ratios were synthesized using random-effects meta-analyses.
Results: Nineteen prospective studies were included, covering overall (k=3), breast (k=10), prostate (k=3), colorectal (k=2), and endometrial (k=1) cancers. Meta-analyses revealed that neither SLE nor PS was consistently associated with increased cancer risk. For perceived stress, results were highly heterogeneous, showing both protective and detrimental effects in specific cohorts, particularly for breast and colorectal cancers. Methodological limitations were prevalent: 63% of studies used non-validated stress measures, 89% assessed stress at only a single time point, and 58% failed to examine the stress-cancer link comprehensively. Consequently, the certainty of evidence was graded as "very low" across all outcomes.
Conclusions/Implications: This systematic review highlights a significant discrepancy between the widespread public perception of stress as a risk factor and the "very low" certainty of the current prospective evidence. The inconsistent associations observed in meta-analyses are heavily influenced by methodological limitations, specifically the reliance on non-validated instruments and single-point assessments that fail to capture the longitudinal nature of chronic stress.
These findings indicate that current epidemiological data are insufficient to support the inclusion of psychological stress in formal cancer prevention guidelines. To advance the field, future research must move beyond fragmented assessments and adopt high-quality, prospective designs using validated, repeated measures.