Abstract
Association of glutathione S-transferase (GST)M1andT1deletions with benign prostate hyperplasia (BPH) and prostate cancer is well reported. These enzymes metabolize numerous toxins thus protecting from oxidative injury. Oxidative stress has been associated with development of BPH and prostate cancer. The present study was designed to analyze role ofGSTdeletions in development of oxidative stress in these subjects. GSTs are responsible for metabolism of toxins present in tobacco therefore effect of tobacco usage in study groups was also studied. Three groups of subjects: BPH (57 patients), prostate cancer (53 patients) and controls (46 subjects) were recruited. Genotyping was done using a multiplex polymerase chain reaction (PCR) method. Malondialdehyde (MDA) levels as marker of oxidative stress were estimated by measuring thiobarbituric acid reactive substance (TBARS) in plasma. Based on genotyping, subjects were categorized into:GSTM1+/GSTT1+, GSTM1-/GSTT1+, GSTM1+/GSTT1- and GSTM1-/GSTT1-. Significantly higher plasma MDA levels were noticed inGSTM1-/GSTT1- as compared toGSTM1+/GSTT1+in all study groups. Double deletion (GSTM1-/GSTT1-) is associated with higher oxidative stress which might play a role in the pathogenesis of BPH and prostate cancer. However, other markers of oxidative stress should be analyzed before any firm conclusion.
Highlights
Benign prostate hyperplasia (BPH) is a non-malignant enlargement of the prostate leading to obstructive lower urinary tract symptoms (LUTs) affecting more than 50% of men by the age 60 years and 90% by 85 years [1]
glutathione S-transferase (GST) enzymes catalyze the conjugation of electrophilic compounds to glutathione and play an important role in the protection of DNA and other macromolecules from oxidative damage
Amongst the principal isoenzymes of GST, GSTM1 is involved in the metabolism of a possible carcinogen, styrene oxide [34]
Summary
Benign prostate hyperplasia (BPH) is a non-malignant enlargement of the prostate leading to obstructive lower urinary tract symptoms (LUTs) affecting more than 50% of men by the age 60 years and 90% by 85 years [1]. Deletion of GSTM1 and GSTT1 genes, which are important isoenzymes of GST, leads to complete lack of activity of their enzymes. Absence of these enzymes due to homozygous deletions are implicated in poor elimination of carcinogenic substances including constituents of tobacco which are potential sources of ROS in our body, making individuals with these deletions susceptible to oxidative injury [10]. Studies have reported positive association of GSTM1 or GSTT1 polymorphism with increased risk of BPH and prostate cancer [11,12,13,14,15]. Recent studies from our laboratory reported association of deletion of both GSTM1 and GSTT1 with markers of oxidative stress like malondialdehyde (MDA) in disorders like diabetic nephropathy, non-diabetic nephropathy and adverse reproductive outcomes [16,17,18]
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