GSTM1 gene expression and copy number variation in prostate cancer patients—Effect of chemical exposures and physical activity

Abstract

BackgroundMany etiological factors have been related to prostate cancer (CaP) development, progression, and survival, such as age, population origin, geographic area, occupational exposures, and nutrition and lifestyle factors. However, physical activity affords health benefits to cancer patients, including those with CaP. Glutathione S-Transferases enzymes have been linked to CaP because of their role in the detoxification of a wide variety of potential carcinogens, steroid hormones and xenobiotics. Among the different glutathione S-transferases isoforms, null genotype for GSTM1 has been associated with an increased risk of CaP, although data are controversial. As the relationship between copy number variation and gene expression of GSTM1 in CaP remains unexplored, this study analyzed GSTM1 gene expression and/or dosage effect on CaP risk and aggressiveness. The potential protective role of physical activity was also explored. MethodsThree hundred and seventeen patients (159 non-CaP and 158 CaP) were recruited from the Service of Urology (Hospital Virgen de las Nieves, Granada, Spain) over the period 2012 to 2014 and were followed-up until January 2018 to ensure a correct classification of control and patients. Individuals were classified in each group based on histological analysis of tissue biopsy, along with data on PSA level, Gleason score and T stage in patients with biopsies positive for CaP. Individuals with a negative biopsy were considered as controls. All controls underwent a systematic 20-core ultrasound guided biopsy in order to limit the false negative rate. Genomic DNA was extracted from peripheral blood to determine the exact copy numbers of GSTM1, and RNA was extracted from prostate tissue samples to determine GSTM1 gene expression. Both analyses were performed using the qPCR method. A questionnaire was administered to all patients to assess environmental exposures, lifestyle, and physical activity. The association of GSTM1 copy number variation and expression with the rest of variables was assessed by chi-square test and the Mann-Whitney test. Multiple logistic regression was used to assess which factors were associated with the risk of CaP. ResultsThe presence of 1 or 2 copies of the GSTM1 gene was not less prevalent in CaP compared to non-CaP patients; however, a significant decreased GSTM1 gene expression was observed in CaP tissue relative to non-CaP tissue (P = 0.003). CaP patients with environmental exposure to dust and smoke, and smoking habit had a significantly decreased GSTM1 gene expression (and near-significantly decreased for living in urban areas) as compared to non-CaP patients with the same exposures. In addition, physical activity was significantly associated with a lower risk of CaP (P = 0.006) and with increased GSTM1 gene expression (P = 0.002). ConclusionsA reduced GSTM1 gene expression in prostate tissue was observed in CaP patients with some environmental chemical exposures. Intriguingly, physical activity might play a protective role against CaP development, possibly as a result of increasing GSTM1 gene expression in prostate tissue. However, this observation warrants further confirmation.