Abstract

Background: Chronic severe psychological stress has long been hypothesized to contribute to cancer development and progression via neuroendocrine, immunological, and inflammatory pathways. However, evidence remains inconsistent and a comprehensive synthesis is lacking.

Objective: This review aims to systematically evaluate existing preclinical and clinical literature, elucidating biological mechanisms by which persistent severe stress may influence carcinogenesis, and to assess epidemiological associations between chronic stress exposure and cancer incidence, progression, or survival.

Methods: We conducted a systematic search of MEDLINE (PubMed), Embase, Web of Science, and publisher databases (Elsevier, Wiley, SAGE, BMC) up to May 2025. Search terms included combinations of “psychological stress,” “chronic stress,” “stressful life events,” “cancer,” “carcinogenesis,” “tumour progression,” and related immunologic, neuroendocrine, and molecular keywords. Two independent reviewers screened titles/abstracts and full texts, applied predefined inclusion and exclusion criteria, extracted data, and assessed risk of bias. The review was carried out following PRISMA guidelines. Both mechanistic (animal / in vitro) and human (observational, clinical) studies were included.

Results: Of 4,312 records identified, 38 full-text articles met inclusion criteria (preclinical mechanistic studies, observational cohort/case–control studies, and systematic reviews). Mechanistic evidence consistently shows that chronic stress induces activation of the hypothalamic–pituitary–adrenal (HPA) axis and sympathetic nervous system (SNS), elevates catecholamines and glucocorticoids, impairs cytotoxic immune surveillance, elevates pro-inflammatory cytokines, promotes angiogenesis and extracellular matrix remodeling, and creates a tumor-permissive microenvironment, thereby facilitating tumor initiation, growth, and metastasis. Clinically, epidemiological findings are mixed: some large meta-analyses report modest positive associations between psychosocial stressors (e.g., depression, anxiety) and overall cancer incidence or mortality, while others find no consistent association. The quality of evidence is limited by heterogeneity in stress definitions, measurement methods, and confounding by lifestyle factors.

Conclusion: Preclinical and translational evidence supports biologically plausible pathways linking persistent severe stress with carcinogenesis and tumor progression. However, human epidemiological evidence remains inconsistent and insufficient to establish causality. Well-designed prospective studies with validated stress measures and biomarker assessment, as well as interventional trials targeting stress pathways, are needed.

Implications for Nursing: Screening for chronic stress, integrating stress-management interventions, and facilitating psychosocial support may contribute to cancer prevention strategies and improve outcomes in clinical care.

Keywords

hronic psychological stress, carcinogenesis, neuroendocrine–immune mechanisms, hypothalamic–pituitary–adrenal axis, tumor progression, epidemiological evidence