ISPO

Androgen receptor CAG repeat polymorphism in prostate cancer from a Brazilian population.

ML Santos, Bsc,a AS Sarkis,PhD, b IN Nishimoto, Ms,c MA Nagai, PhD a

a Departamento de Radiologia, Universidade de Sao Paulo, bDivisão de Clínica Urológica, Depto de Urologia, HC-FMUSP, c Hospital AC Camargo, São Paulo, Brazil

Prostate cancer is the most commonly diagnosed malignancy and the second leading cause of mortality related to cancer in men living in the Western world. The first exon of the androgen receptor gene (AR) contains two polymorphic trinucleotide repeat regions that encode polyglutamine (CAG) and polyglycine (GGN) tracts localized in the NH2-terminal transactivation domain of the AR protein. There is an inverse linear relation between CAG repeat lenght and AR transactivation activity. Shorter AR polyglutamine tracts have been associated with increased prostate cancer risk. The aim of the present work is to investigate whether the AR CAG polymorphism is associated with an increased relative risk for prostate cancer in our population. Genomic DNA from 133 prostate cancer patients and 279 healthy men controls were examined to determine the number of CAG repeats. The number of CAG repeats was determined through PCR amplification, direct DNA sequencing and by denaturing polyacrilamide gel eletrophoresis. Confirming previous studies our results show that Asian individuals have the highest CAG repeats rates, white an intermediate and black a tendency to the lowest CAG repeats rates. A 51% OR=1,51 (1,0-2,4) increased risk of prostate cancer was found in individuals with a CAG repeat length of 21 or less. We also did find a significant correlation between a lower number of CAG repeats and young age at diagnosis. Studies involving androgen receptor may help to determine a well-defined prostate tumorigenesis model, thus contributing to the accuracy of diagnosis, prognosis and treatment of prostate cancer.

KEY WORDS: prostate cancer, androgen receptor, CAG repeat polymorphism.

For more information, contact nagai@usp.br

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Prognostic Markers.

http://www.cancerprev.org/Journal/Issues/26/101/1294/4487