ABSTRACT
Background & objectives: Wide variability in serum prostate specific antigen (PSA) levels exists in malignant conditions of the prostate. PSA is expressed in normal range in 20 to 25 per cent of prostate cancer cases even in presence of high grade Gleason score. This study was aimed to assess the influence of genetic variants exhibited by PSA and androgen receptor (AR) genes towards the variable expression of PSA in prostate cancer. Methods: Pre-treatment serum PSA levels from 101 prostate cancer cases were retrieved from medical record. PSA genotype analysis in promoter region and AR gene microsatellite Cytosine/Adenine/Guanine (CAG) repeat analysis in exon 1 region was performed using DNA sequencing and fragment analysis techniques. Results: A total of seven single nucleotide polymorphisms (SNPs) in the PSA promoter region were noted. Only two SNPs viz., 158G/A (P<0.001) in the proximal promoter region and -3845G/A (P<0.001) in enhancer region showed significant association with serum PSA levels. The carriers of homozygous GG genotype (P<0.001) at both of these polymorphic sites showed higher expression of PSA whereas homozygous AA genotype (P<0.001) carriers demonstrated lower PSA levels. The combination effect of PSA genotypes along with stratified AR CAG repeats lengths (long, intermediate and short) was also studied. The homozygous GG genotype along with AR long CAG repeats and homozygous AA genotype along with AR short CAG repeats at position -3845 and -158 showed strong interaction and thus influenced serum PSA levels. Interpretation & conclusions: The genetic variants exhibited by PSA gene at positions -3845G/A and -158G/A may be accountable towards wide variability of serum PSA levels in prostate cancer. Also the preferential binding of G and A alleles at these polymorphic sites along with AR long and short CAG repeats may contribute towards PSA expression.
ABSTRACT
Background & objectives: Serum prostate specific antigen (PSA) though most commonly used for diagnosis of prostate cancer lacks specificity. This study was aimed at exploring the use of serum glyoxalase as a supplemental biomarker to differentiate between malignant vs non-malignant diseases of the prostate in patients with PSA in the range of 4-20 ng/ml. Methods: Serum glyoxalase and PSA were measured in 92 men (30 control, 31 cases of benign prostate hyperplasia (BPH) and 31 cases of adenocarcinoma of prostate). Of the latter group, 11 cases of prostate cancer in the PSA range of 4-20 ng/ml were included for studying the diagnostic utility of combination of both serum PSA and glyoxalase. Results: In prostate cancer cases with PSA in the range of 4-20 ng/ml, the glyoxalase was found to be 233.3 ± 98.6 μmol/min while for the non-malignant group it was 103.1 ± 19.7 μmol/min. A cut-off of 19.2 ng/ml PSA showed sensitivity of 9 per cent, specificity of 96.7 per cent, positive predictive value (PPV) of 50 per cent and negative predictive value (NPV) of 75 per cent. A serum glyoxalase cut-off of 141 μmol/min showed sensitivity of 81.8 per cent, specificity of 100 per cent, PPV of 100 per cent and NPV of 93.9 per cent. Further, ROC analysis showed a significant difference in the area under curve (AUC) for glyoxalase as compared to serum PSA (0.92 vs 0.57; P<0.001). Interpretation & conclusions: Serum glyoxalase appears to be predictive of prostate cancer in the PSA range of 4-20 ng/ml. Studies with larger number of participants would be required to confirm this finding.