RT Journal Article
SR Electronic
T1 A G/A Polymorphism in the Androgen Response Element 1 of Prostate-specific Antigen Gene Correlates with the Response to Androgen Deprivation Therapy in Japanese Population
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 3365
OP 3371
VO 26
IS 5A
A1 SHIBAHARA, TAKUJI
A1 ONISHI, TAKEHISA
A1 FRANCO, OMAR E.
A1 ARIMA, KIMINOBU
A1 NISHIKAWA, KOHEI
A1 YANAGAWA, MAKOTO
A1 HIOKI, TAKUICHI
A1 WATANABE, MASATOSHI
A1 HIROKAWA, YOSHIFUMI
A1 SHIRAISHI, TAIZO
A1 SUGIMURA, YOSHIKI
YR 2006
UL http://ar.iiarjournals.org/content/26/5A/3365.abstract
AB Prostate-specific antigen (PSA) gene expression is regulated by androgen receptor (AR) through androgen response elements (AREs) in the promoter region of the PSA gene. A single nucleotide polymorphism with guanine (G) to adenine (A) substitution is identified at position -158 in the ARE of the PSA gene. The purpose of this study was to investigate the allelic differences in the PSA promoter activity in vitro and the relation to several clinical factors of prostate cancer patients in the Japanese population. No significant differences of promoter activity in luciferase assay and binding activity of androgen receptor were noted between the two alleles in vitro. The PSA -158 G/A polymorphism was determined by PCR amplification and restriction digestion assays in 101 organ-confined prostate cancer (PC) patients who underwent radical prostatectomy and 52 controls with benign prostatic hyperplasia. The results revealed that homozygosity for the A allele in Japanese is less common (only 8.5%) than in ethnic populations. There were no significant differences in serum PSA value at the time of diagnosis, differentiation of cancer, pathological stage, cancer volume or ratio of serum PSA/cancer volume. However, cancer volume after neoadjuvant endocrine therapy was significantly smaller in GG genotype than in AA + AG genotypes. Our data indicate that the PSA -158 G/A polymorphism has no effect on the PSA promoter activity in vitro and no association with the serum PSA level in Japanese men, however suggest that the patients with GG genotype of ARE1 may be more sensitive to androgen ablation therapy. Taken together, the ARE1 polymorphism in the PSA gene promoter may be one of the biomarkers for response to androgen deprivation therapy. Copyright© 2006 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved