title: The presence of the CYP11A1 (TTTTA)6 allele increases the risk of biochemical relapse in organ confined and low-grade prostate cancer.
abstract: The involvement of the CYP11A1 gene in the synthesis of androgens makes it a compelling candidate for various hormone-dependent diseases, including prostate cancer. A microsatellite polymorphism (TTTTA)n in the promoter region of the CYP11A1 gene has been reported to be associated with an increased risk of metastatic and high-grade prostate cancer. In the present study of 110 prostate cancer patients and 96 population controls, we examined the association between the CYP11A1 (TTTTA)n polymorphism and prostate cancer risk, aggressiveness, and incidence of biochemical relapse after prostatectomy. We have also evaluated the potential of the (TTTTA)n polymorphism as a microsatellite marker for the detection of genomic instability in prostate cancer. A strong association of the genotype containing the (TTTTA)6 allele with the occurrence of biochemical relapse after prostatectomy in patients with organ confined prostate cancer (p<0.0001), as well as in patients with low-grade prostate cancer (p=0.002) or both (p<0.0003) was determined. The incidence of biochemical relapse in patients with organ confined and low-grade prostate cancer in our study group was 22%, but increased to 50% in carriers of the (TTTTA)6 allele. Our findings also suggest (TTTTA)n instability as a potential marker for the detection of early events in carcinogenesis.
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Askerceva 7, SI-1000 Ljubljana, Slovenia.
authors.forename: Teja
authors.initials: T
authors.lastname: Celhar
authors.forename: Ksenija
authors.initials: K
authors.lastname: Gersak
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Ovcak
authors.forename: Boris
authors.initials: B
authors.lastname: Sedmak
authors.forename: Irena
authors.initials: I
authors.lastname: Mlinaric-Rascan
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001483:Base Sequence; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics*; D005834:Genital Neoplasms, Male / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D012008:Recurrence; D012016:Reference Values; D012307:Risk Factors; D012669:Seminal Vesicles / Q000473:pathology*; D017524:Slovenia
chemical_list: D002786:Cholesterol Side-Chain Cleavage Enzyme