Chronic Psychosocial Stress and Cancer Risk: Exploring Neuroendocrine, Immunological, and Molecular Mechanisms of Psychosocial Carcinogenesis

Abstract

Chronic psychosocial stress has increasingly been recognized as a potential modifier of cancer risk and progression through complex neuroendocrine, immunological, and molecular pathways. While the concept of “psychogenic carcinogenesis” remains controversial, accumulating evidence suggests that sustained activation of stress-response systems may influence tumor biology. This review explores the mechanistic links between chronic psychiatric stressors—including depression, anxiety disorders, and prolonged emotional distress—and carcinogenesis. Persistent activation of the hypothalamic–pituitary–adrenal (HPA) axis and sympathetic nervous system results in elevated cortisol and catecholamine levels, which may impair immune surveillance, promote chronic inflammation, and alter cellular signaling pathways. Stress-induced immunosuppression can reduce natural killer (NK) cell activity and T-cell–mediated tumor defense, potentially facilitating tumor initiation and progression. Additionally, chronic inflammation mediated by cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) may contribute to DNA damage, epigenetic modifications, and enhanced tumor microenvironment remodeling. Emerging data also indicate that stress hormones can influence proto-oncogene activation, angiogenesis, and metastatic potential via β-adrenergic signaling pathways. Behavioral factors associated with psychiatric conditions—including smoking, alcohol consumption, poor diet, and reduced treatment adherence—may further compound cancer risk through indirect carcinogenic mechanisms. Although current evidence does not establish psychosocial stress as a direct carcinogen, it supports its role as a biological and behavioral modulator of tumor development and progression. Understanding these multidimensional interactions is essential for integrating psychosocial care into comprehensive cancer prevention and management strategies. Future longitudinal and molecular studies are required to clarify causal relationships and identify potential therapeutic targets within stress-mediated oncogenic pathways.