Role of stress in the pathogenesis of cancer (Review).

Stress is a state of disrupted homeostasis, triggered by intrinsic or extrinsic factors, the stressors, which are counteracted by various physiological and behavioural adaptive responses. Stress has been linked to cancer development and incidence for decades; however, epidemiological studies and clinical trials have yielded contradictory results. The present review discusses the effects of stress on cancer development and the various underlying mechanisms. Animal studies have revealed a clear link between stress and cancer progression, revealing molecular, cellular and endocrine processes that are implicated in these effects. Thus, stress hormones, their receptor systems and their intracellular molecular pathways mediate the effects of stress on cancer initiation, progression and the development of metastases. The mechanisms linking stress and cancer progression can either be indirect, mediated by changes in the cancer microenvironment or immune system dysregulation, or direct, through the binding of neuroendocrine stress­related signalling molecules to cancer cell receptors. Stress affects numerous anti­ and pro­cancer immune system components, including host resistance to metastasis, tumour retention and/or immune suppression. Chronic psychological stress through the elevation of catecholamine levels may increase cancer cell death resistance. On the whole, stress is linked to cancer development and incidence, with psychological stressors playing a crucial role. Animal studies have revealed a better link than human ones, with stress­related hormones influencing tumour development, migration, invasion and cell proliferation. Randomized controlled trials are required to further evaluate the long­term cancer outcomes of stress and its management.

Childhood experiences of parenting and cancer risk at older ages: findings from the English Longitudinal Study of Ageing (ELSA).

OBJECTIVES: Despite the importance of childhood experiences for adult health and psychosocial factors for cancer development, parenting, a key childhood psychosocial exposure, has yet to be studied in relation to cancer risk at older ages. We examined whether childhood experiences of poor-quality parenting are associated with an increased risk of cancer at older ages. METHODS: We used a sample of 4471 community dwellers aged ≥ 55 years in 2007. Poor-quality parenting was defined as low levels of parental care and high levels of parental overprotection. RESULTS: Overall poorer experiences of parenting, decreasing parental care and increasing parental overprotection were associated with increased risk of incident all-site and skin cancer in men, but not in women. Increasing paternal overprotection was also associated with increased risk of incident colorectal cancer in men. Overall poorer experiences of parenting and increasing paternal overprotection were associated with increased risk of prevalent all-site and colorectal cancer in women. Adjustment for covariates explained a small part of these associations. CONCLUSIONS: Older adults who reported childhood experiences of poorer quality parenting appear to have an increased risk of cancer. These findings improve our understanding of the role of psychosocial factors in cancer over the life course.

Protein expression in the brain of rat offspring in relation to prenatal caloric restriction.

OBJECTIVE: Intrauterine growth restriction (IUGR) has been associated with decreased supply of crucial substrates to the fetus and affects its growth and development by temporarily or permanently modifying gene expression and function. However, not all neonates born by calorie restricted mothers are IUGR and there are no reports regarding their brain protein expression vis-à-vis that of their IUGR siblings. Here, we investigated the expression of key proteins that regulate growth and development of the brain in non-IUGR newborn pups versus IUGR siblings and control pups. METHODS: Rat brain proteins were isolated from each group upon delivery and separated by two-dimensional gel electrophoresis (2-DE). RESULTS: 14-3-3 Protein, calreticulin, elongation factor, alpha-enolase, fascin, heat-shock protein HSP90 and pyruvate kinase isozymes were significantly increased (p < 0.05) in samples obtained from IUGR newborn pups compared to non-IUGR. Conversely, collapsin response mediator proteins, heat-shock70 and peroxiredoxin2 were decreased in IUGR group compared to non-IUGR. CONCLUSIONS: In our experimental study, IUGR pups showed an altered proteomic profile compared to their non-IUGR siblings and non-IUGR controls. Thus, not all offspring of calorie-restricted mothers become IUGR with the accompanying alterations in the expression of proteins. The differentially expressed proteins could modulate alterations in the energy balance, plasticity and maturation of the brain.