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

尽管对压力与癌症之间的联系进行了大量的研究，但结果仍然没有定论。评估这种联系的一种有用但很少应用的方法是同时检查心理压力和易患癌症的基因改变之间的关系。我们调查了156名健康工人（116名男性和40名女性）外周血白细胞中8-羟基脱氧鸟苷（8-OH-dG）的水平是否与各种心理因素有关。8-OH-dG是癌症相关氧化DNA损伤的生物标志物。我们还通过中性粒细胞的激活和中性粒细胞的活性氧的产生，研究了心理应激相关的8-OH-dG产生的机制。此外，我们比较了抑郁患者与年龄和性别匹配的健康对照组的8-OH-dG水平，并分析了8-OH-dG水平的相关因素。女工8-OH-dG水平与一般健康问卷抑郁得分呈正相关，与一般健康问卷社交功能障碍得分呈负相关。另一方面，男性工人的8-OH-dG水平与美国流行病学研究中心抑郁量表的抑郁得分呈正相关。外周中性粒细胞数量与8-OH-dG水平无显著关系。抑郁症患者血清8-OH-dG水平显著高于健康对照组；然而，在抑郁症和对照组中没有发现与8-OH-dG水平相关的因素。这些发现不仅提供了压力-癌症关联的证据，而且还提示了压力相关癌症发生机制的可能性别差异。

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.