It is widely recognized that
androgen biosynthesis and metabolism are associated with the development and progression of
prostate cancer. The human
CYP11A1 gene (
CYP11A1) encodes the P450scc
enzyme, which mediates the first step in
sex steroid hormone synthesis. The gene contains a (tttta)n-5 bp tandem repeat microsatellite polymorphism located at 528 bp upstream of the translation initiation site and the
CYP11A1 mRNA level may be modulated by the polymorphism. Recent studies suggested that the absence of the shortest (tttta)4 allele of the
CYP11A1 polymorphism was associated with a risk of
polycystic ovary syndrome and with a hyperandrogenic state in
polycystic ovary syndrome patients. In our study which included 278
prostate cancer patients, 213
benign prostatic hyperplasia (BPH) patients and 299 male controls, we explored the association between the
CYP11A1 polymorphism and
prostate cancer on the hypothesis that the presence of the (tttta)4 allele may increase the risk of the development or progression of
prostate cancer. In addition, we measured the serum levels of 6
steroid hormones or their metabolite (i.e.,
testosterone, free-
testosterone,
estrone,
estradiol,
dehydroepiandrosterone and androstendione) in 156 control males subjects and compared those with and without the (tttta)4 allele. The polymorphism was evaluated by PCR amplification of
a 145-170 bp fragment followed by polyacrylamid gel electrophoresis. The
CYP11A1 allele consisted of 4, 6, 7, 8 and 9 (tttta)-5 bp repeats. There was no significant difference in the genotype frequency as for the presence of the (tttta)4 allele between
prostate cancer patients and male controls, and between
prostate cancer patients and BPH patients. However, there was a significant difference in the genotype frequency in relation to the disease status.
Prostate cancer patients without the (tttta)4 allele had an increased risk of metastatic disease (stage D) compared to those with the (tttta)4 allele [adjusted odds ratio (aOR)=1.76, 95% confidence interval (Cl)=1.07-2.90 and p =0.026]. Patients without the (tttta)4 allele had an increased risk of high grade
prostate cancer (Gleason score 8 or more, or poorly differentiated
cancer) compared to those with the (tttta)4 allele (aOR=1.79, 95% Cl=1.08-2.97 and p =0.025). No significant difference in the serum levels of 6
steroid hormones or their metabolites was found in the presence or absence of the (tttta)4 allele. Our results suggest that the
CYP11A1 polymorphism may have a significant influence on the development of advanced and/or high grade
prostate cancer and the absence of the
CYP11A1 (tttta)4 allele, i.e., the homozygosity for the (tttta)6 or longer allele, could be a useful marker for the prediction of
disease progression of
prostate cancer.