GGN repeat length and GGN/CAG hapotype variations in the androgen receptor gene and prostate cancer risk in South Indian men

Department of Human Genetics, Sri Ramachandra Medical College and Research Institute Deemed University, Porur, Chennai, 600116 Tamil Nadu, India.
Journal of Human Genetics (Impact Factor: 2.46). 10/2006; 51(11):998-1005. DOI: 10.1007/s10038-006-0051-z
Source: PubMed


The ethnic variation in the GGN and CAG microsatellites of the androgen receptor (AR) gene suggests their role in the substantial racial difference in prostate cancer risk. Hence, we performed a case-control study to assess whether GGN repeats independently or in combination with CAG repeats were associated with prostate cancer risk in South Indian men. The repeat lengths of the AR gene determined by Gene scan analysis, revealed that men with GGN repeats <or=21 had no significant risk compared to those with >21 repeats (OR 0.91 at 95% CI-0.52-1.58). However, when CAG repeats of our earlier study was combined with the GGN repeat data, the cases exhibited significantly higher frequency of the haplotypes CAG <or=19/GGN <or=21 (OR-5.2 at 95% CI-2.17-12.48, P < 0.001) and CAG <or=19/GGN > 21(OR-6.9 at 95%CI-2.85-17.01, P < 0.001) compared to the controls. No significant association was observed between GGN repeats and prostate-specific antigen levels and the age at diagnosis. Although a trend of short GGN repeats length in high-grade was observed, it was not significant (P = 0.09). Overall, our data reveals that specific GGN/CAG haplotypes (CAG <or=19/GGN <or=21 and CAG <or=19/GGN > 21) of AR gene increase the risk of prostate cancer and thus could serve as susceptibility marker for prostate cancer in South Indian men.

Download full-text


Available from: Solomon Paul,
18 Reads
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Disparities in prostate cancer incidence and outcomes are a hallmark of the global pattern of prostate cancer, with men of African descent suffering disproportionately from this disease. The causes of these disparities are poorly understood. A review of the literature was undertaken to evaluate the role that genetic susceptibility may play in prostate cancer etiology and outcomes, with a particular emphasis on disparities. The genetic contribution to prostate cancer is well established, and a number of candidate prostate cancer genes have been identified. Significant differences in the frequency of risk alleles in these genes have been identified across the major races. These allele frequency differences may in part explain an increased susceptibility to prostate cancer in some populations. In addition, non-genetic factors contribute significantly to prostate cancer disparities, and the cumulative contribution of both genetic and non-genetic factors to poor-prognosis prostate cancer may explain the poorer outcomes experienced by men of African descent. Prostate cancer disparities are a function of genetic susceptibility as well as environment, behavior, and health care factors acting in the context of this genetic susceptibility. Elimination of global prostate cancer disparities requires a full understanding of the effects of all of these factors on prostate cancer etiology and outcomes.
    The Canadian Journal of Urology 03/2008; 15(1):3872-82. · 0.98 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: There is apparent uncertainty in etiology and pathogenesis of Benign Prostatic Hyperplasia. Though several hypothesis put forwarded, like other multifactorial complex diseases, BPH still lacks an integrated model of pathogenesis and progression. BPH is a common problem of aged men due uncontrollable non-cancerous prostatic growth. A wide variety of genetic factors have been associated with tissue hyperplasia in general. Androgen related genes and metabolism genes are closely associated with growth and function of prostate. Recent emergence of BPH as inflammation-mediated disease also opens new avenues in search for genetic factors of BPH. Knowledge of gene polymorphisms may be an important aid in genetic screening of risk of disease involved and the understanding of complex interactions involved in genesis and progression of BPH. Till to date there is no report of high penetrance genetic marker in BPH. There is immense possibility of evolving a model of low penetrance markers of BPH and with this prospect a more exhaustive search for all BPH associated polymorphism in larger population is needed. This strategy combined with high-throughput expression profiling and linkage studies of genes for establishing a clear picture of pathophysiology and risk factor of a complex disease like BPH. In this study, we have reviewed a variety of genetic polymorphisms in relation to their possible role in benign prostatic hyperplasia. We have included associations identified in molecular epidemiology studies and the consistency of findings reported to date. Suggestions for further research are also offered. Keyword: Polymorphism, Benign Prostatic Hyperplasia, Pathogenesis
    BJU International 05/2008; 102(5):536-44. DOI:10.1111/j.1464-410X.2008.07667.x · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Acne vulgaris is one of the most common skin disorders, and androgen is known to play a key role in the development of acne. However, the exact genetic mechanism by which androgen receptor (AR) gene affects acne development is still unclear. Our study aimed to investigate whether CAG and GGN polymorphism of the AR gene are associated with acne risk. Two hundred thirty-eight patients and 207 controls were included in the study. The repeat lengths of the AR gene were determined by GeneScan analysis. Men with CAG < 23 and women with CAG < 24 had significant risk compared to those men with CAG > or = 23 [odds ratio (OR), 2.07; 95% confidence interval (95% CI), 1.21-3.54] and women with CAG > or = 24 (OR, 2.05; 95% CI, 1.18-3.56). In males, GGN repeats, considered independently of the CAG repeat, have no significant effect on the acne risk; however, when combined with CAG repeats, the acne patients exhibited significantly higher frequency of the haplotypes CAG < 23/GGN < or = 23 (OR, 3.33; 95% CI, 1.10-10.07; P < 0.05) compared with the controls. Our results of this study strongly indicated that a shorter CAG repeat length and specific haplotypes of AR attributed to the risk of acne development and thus could serve as a susceptibility marker.
    Journal of the European Academy of Dermatology and Venereology 07/2008; 22(12):1445-51. DOI:10.1111/j.1468-3083.2008.02891.x · 2.83 Impact Factor
Show more