Deeply Saddening Life Events Play a Carcinogenic Role by Inducing Mutations in ALOX12 and FKBP5 Genes

Abstract

Background/Objectives: In the past few decades, many studies have been conducted to find out that psychological stress and cancer are closely linked. Moreover, it was reported that stress can induce mutations in gene level. Therefore, in this study we want to examine a relationship between stressful life events, gene mutation and cancer. Methods: Stressful Life Experiences Screening (SLES), Hospital Anxiety and Depression Scale (HADS) and the Coping with Stress Style Scale (CSS) were applied to the participants to examine relationship between stress and cancer. Results: NGS results showed higher level of mutations accumulated on FKBP5 and ALOX12 genes in cancer patients who were exposed to stressful life events. The expression status of ALOX12 and FKBP5 genes on patients with or without cancer and several cancer cell lines demonstrated that both ALOX12 and FKBP5 mRNA levels were downregulated only in cancer patients and cancer cell lines but not in cancer free control groups. Re-created overexpression of the WT-ALOX12 and WT-FKBP5 extremely inhibited cellular growth, cellular invasion in cancer cell lines, tumor growth in xenograft model too. Conclusions: Our results indicate that Stressful Life Experiences may induce cancer development by increased somatic mutations in ALOX12 and FKBP5 genes.