title: Androgen receptor GGC polymorphism and testosterone levels associated with high risk of prostate cancer and benign prostatic hyperplasia.
abstract: Polymorphic GGC repeats in the androgen receptor (AR) gene can alter transactivation of androgen-responsive genes and increase the risk of benign prostatic hyperplasia (BPH) and prostate cancer (PCa). We investigated the association between GGC repeat length, testosterone levels and the risk of developing PCa and BPH in a population from southern Brazil. A sample comprising 130 PCa, 126 BPH and 88 control patients was evaluated. DNA was extracted from leukocytes and the AR gene was analyzed by fragment analysis. The hazard ratio (HR) was estimated. GGC mean length was not different between the three study groups. The risk of developing PCa in individuals with GGC > 19 was 3.300 (95 %CI 1.385-7.874) higher when compared to the GGC ≤ 19 group (p = 0.007). The risk of developing PCa and BPH in individuals with total testosterone levels <4 ng/mL was 2.799 (95 % CI 1.362-5.754). (p = 0.005) and 2.786 (95 % CI 1.470-5.280) (p = 0.002), respectively. Total testosterone levels in patients with GGC > 19 were significantly lower when compared to patients in the GGC ≤ 19 group. Our data suggest that the presence of a high number of polymorphic GGC repeats in the AR gene is associated with an increased risk of developing PCa and BPH, and that lower testosterone levels also increase the risk of developing these diseases.
authors.affiliation: Department of Physiology, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite 500, CEP 90050-170, Porto Alegre/RS, Brazil. vbiolchi@gmail.com
authors.forename: Vanderlei
authors.initials: V
authors.lastname: Biolchi
authors.forename: Brasil
authors.initials: B
authors.lastname: Silva Neto
authors.forename: Diego Bromfman
authors.initials: DB
authors.lastname: Pianta
authors.forename: Walter José
authors.initials: WJ
authors.lastname: Koff
authors.forename: Milton
authors.initials: M
authors.lastname: Berger
authors.forename: Ilma Simoni
authors.initials: IS
authors.lastname: Brum
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001938:Brazil; D016022:Case-Control Studies; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D011470:Prostatic Hyperplasia / Q000097:blood* / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D011944:Receptors, Androgen / Q000235:genetics*; D012306:Risk; D013739:Testosterone / Q000097:blood*; D018911:Trinucleotide Repeats
chemical_list: D011944:Receptors, Androgen; D013739:Testosterone