Abstract for presentation at 11th International Congress of Human Genetics

Prostate Specific Antigen(PSA) gene polymorphism and its Interaction with Androgen Receptor Trinucleotide Repeats (CAG) in Prostate Cancer

  • Dr Rama Mittal, Sanjay Gandhi Post Graduate Institute of Medical Sciences, India
  • Mr Dhruva Mishra, Sanjay Gandhi Post Graduate Institute of Medical Sciences, India
  • Dr Anil Mandhani, Sanjay Gandhi Post Graduate Institute of Medical Sciences, India
  • Dr Anant Kumar, Sanjay Gandhi Post Graduate Institute of Medical, India

    • Purpose: Prostate cancer (CaP) is the fourth most common malignancy among men in world. Androgens play an important role in the development and differentiation of prostate. It has been hypothesized that variation in transcriptional activity by the androgen receptor (AR) related to polymorphic CAG repeats in exon 1, influences CaP risk. Androgen receptor regulates gene transcription by binding to androgen-response elements (AREs) in target genes, such as the prostate-specific antigen (PSA). An adenine to guanine polymorph¬ism has been reported in the ARE-I sequence of the PSA gene. It has also been assumed that the AR binds the two PSA alleles (A and G) with differing affinities and may, thereby, differentially influence CaP risk.
    Methods:We conducted a case-control study of North Indian population with 135 CaP patients and 142 age-matched healthy control men to observe the role of the polymorphisms in the AR and PSA genes in CaP risk. Blood leukocyte DNA was extracted from each sample and CAG repeat in AR gene was determined by PCR-GenScan method while PSA polymorphism was detected by PCR-RFLP method. Logistic regressions were performed to calculate odds ratios (OR) and confidence interval (CI) and also with other confounders.
    Results:Our data provide evidence for an association between CaP and short CAG repeat length (p<0.01). However, no significant association of the ARE-I PSA polymorphism on prostate cancer risk was found. In a case analysis according to Gleason score, the PSA G/G genotype was significantly more frequent in patients with Gleason score >7 than Gleason score <7 (OR= 5.58 95% CI 2.05-15.18; p= 0.001), providing evidence that the PSA G/G genotype is associated with more advanced disease at time of diagnosis. In a combinatorial analysis of short CAG repeat and PSA genotype no significant increased risk was observed.
    Conclusion:Thus, our study supports the role of CAG repeat in increasing the risk of CaP and an ambivalent role of PSA during prostate carcinogenesis.

    Conference Organiser - ICMS Pty Ltd