FKBP5 Polymorphisms As Vulnerability to Anxiety and Depression in Patients with Advanced Gastric Cancer: a Controlled and Prospective Study

Cancer patients, who have to adapt to a long treatment process with multiple stressful events, show various stress responses. Genetic components may contribute to individual differences in stress response and risk for development of stress-related psychiatric problems. The present study aimed to investigate the influence of FK506 binding protein 5 (FKBP5) gene polymorphisms regulating the hypothalamic-pituitary-adrenal (HPA) axis on individual distress levels in cancer patients faced with similar stressful situation. The present study used a prospective design to elucidate predictors of distress. A total of 130 patients (90 males, 40 females) who were newly diagnosed with advanced gastric cancer and supposed to receive first-line chemotherapy were initially assessed, and a six-week follow-up assessment occurred for 93 patients (63 males, 30 females) after two cycles of chemotherapy. Distress levels and coping patterns were measured by the Hospital Anxiety and Depression Scale (HADS) and Mini-Mental Adjustment to Cancer (Mini-MAC) scale. For genetic factors, three single nucleotide polymorphisms of FKBP5 rs1360780, rs9296158 and rs9470080 were genotyped. For HADS-anxiety, FKBP5 rs9296158 had a significant group-by-time interaction (p=0.015), and rs9470080 and rs1360780 had a marginally significant interaction (p=0.023, p=0.038, respectively). For HADS-depression, rs9470080 and rs9296158 had a marginally significant group-by-time interaction (p=0.026, p=0.032, respectively). In addition, a step-wise linear regression analysis showed that FKBP5 rs9470080 and rs9296158 were significant predictors of anxiety and depression after prolonged stress exposure in cancer patients. Our findings indicate that the genetic factors regulating the HPA axis such as FKBP5 gene polymorphisms may play a crucial role in anxiety and depression following prolonged stress exposure.