Relationship between psychological and occupational stress and cancer risk due to oxidative DNA damage

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Although numerous studies have been carried out on the stress-cancer linkage, the results still inconclusive. One of the useful, but rarely applied, method to assess this linkage is to examine the relationship between psychological stress and cancer prone genetic alterations simultaneously. We investigated whether various psychological factors can be associated with the levels of 8-hydroxydeoxyguanosine (8-OH-dG), a biomarker of cancer-related oxidative DNA damage, in peripheral blood leukocytes in 156 healthy workers (116 males and 40 females). We also examined the mechanism of psychological stress-associated production of 8-OH-dG through the activation of neutrophils and the production of reactive oxygen species from the neutrophils. In addition, we compared the 8-OH-dG levels between depressive patients and healthy age- and sex-matched controls, and analyzed the factors relevant to the 8-OH-dG levels. The levels of 8-OH-dG in female workers were positively correlated with the depression scores of the General Health Questionnaire (GHQ), and negatively associated with the social dysfunction scores of the GHQ. On the other hand, the levels of 8-OH-dG in male workers were positively correlated with the depression scores of the Center for Epidemiologic Studies Depression Scale. No significant relationship was found between the number of peripheral neutrophils and the 8-OH-dG levels. The levels of 8-OH-dG in patients with depression were significantly higher than those in healthy controls; however, no factors were found to be associated with the 8-OH-dG levels in the depressive and control subjects. These findings not only provide evidence of a stress-cancer linkage, but also suggest possible sex differences in the mechanisms of stress-related cancer initiation.