Polymorphic forms of prostate specific antigen and their interaction with androgen receptor trinucleotide repeats in prostate cancer.
BACKGROUND
Recent data has suggested that polymorphisms in the prostate specific antigen (PSA) may increase prostate cancer (PC) risk. The PSA gene contains a G/A substitution in the androgen response element (ARE) 1 region. The androgen receptor (AR) gene has polymorphic regions containing variable length glutamine and glycine repeats and these are believed to be associated with PC risk. The effect on PC risks from PSA polymorphisms alone and synergistically with the AR gene was examined in this report.


METHODS
One hundred PC patients and an age matched cohort of 79 benign prostate hyperplasia and 67 population controls were entered in this study. DNA was extracted from blood and PSA/ARE promoter region amplified by PCR. PCR products were cut with Nhe 1 restriction enzyme to distinguish G/A alleles. AR/CAG and GGC repeat length was detected by automated fluorescence from PCR products.


RESULTS
We found a significantly higher PSA/GG distribution in PC (30%) than either benign prostatic hyperplasia (BPH) (18%) or population controls (16%) (P = 0.025). Furthermore the GG distribution within cases was even greater in younger men (< 65 years; 42%; P = 0.012). Additionally, when PSA genotype was cross classified with CAG repeat, significantly more cases than both BPH and population controls were observed to have a short (< 22) CAG/GG genotype (P = 0.006).


CONCLUSIONS
Our results indicate that the PSA/ARE GG genotype confers an increased risk of PC especially among younger men. Moreover, we confirm previous results that a short glutamine repeat in conjunction with GG genotype significantly increases the risk of malignant disease.
Binnie
Margaret C
MC
Prostate Research Group, Division of Oncology, School of Molecular and Clinical Medicine, Western General Hospital, Edinburgh, United Kingdom.
Alexander
Freda E
FE
Heald
Charlotte
C
Habib
Fouad K
FK
D000368:Aged; D016022:Case-Control Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017430:Prostate-Specific Antigen / Q000235:genetics* / Q000378:metabolism*; D011470:Prostatic Hyperplasia / Q000235:genetics; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism*; D012042:Registries; D020218:Response Elements / Q000235:genetics; D012307:Risk Factors; D018911:Trinucleotide Repeats
D011944:Receptors, Androgen; D017430:Prostate-Specific Antigen