Germline Mutation Analysis of the Androgen Receptor Gene in Finnish Patients With Prostate Cancer
Abstract
Purpose:
Steroid hormones, particularly androgens, are suspected to have a major role in prostate carcinogenesis. Since androgen receptor mediates androgenic effects on cells and recent studies suggest that the androgen receptor gene is a putative prostate cancer susceptibility locus, we screened the coding region of the androgen receptor gene for germline mutations using the genomic DNA of patients with prostate cancer.
Materials and Methods:
DNA samples from 38 patients with early onset prostate cancer and 36 from Finnish prostate cancer families showing no male-to-male transmission of prostate cancer were analyzed for mutations in the androgen receptor gene using single strand conformation polymorphism analysis and subsequent sequencing.
Results:
R726L substitution in the hormone binding region of androgen receptor was found in 1 prostate cancer family but no previously uncharacterized germline mutations were detected.
Conclusions:
Our results indicate that constitutional androgen receptor mutations explain only a small fraction of familial and early onset prostate cancer cases in Finland.
References
- 1 : Genetic predisposition to prostate cancer. Prostate Cancer Prostatic Dis1999; 2: 9. Google Scholar
- 2 : Perspective: prostate cancer susceptibility genes. Endocrinology2002; 143: 2029. Google Scholar
- 3 : A review of genetic polymorphisms and prostate cancer risk. Ann Epidemiol2002; 12: 182. Google Scholar
- 4 : Clinical review 134: the endocrinology of prostate cancer. J Clin Endocrinol Metab2001; 86: 3467. Google Scholar
- 5 : Molecular biology of the androgen receptor. J Clin Oncol2002; 20: 3001. Google Scholar
- 6 : Androgen receptor gene alterations and chromosomal gains and losses in prostate carcinomas appearing during finasteride treatment for benign prostatic hyperplasia. Clin Cancer Res1999; 5: 3578. Google Scholar
- 7 : Two percent of Finnish prostate cancer patients have a germ-line mutation in the hormone-binding domain of the androgen receptor gene. Cancer Res2000; 60: 6479. Google Scholar
- 8 : R726L androgen receptor mutation is uncommon in prostate cancer families in the United States. Prostate2003; 54: 306. Google Scholar
- 9 : Identification of two germline point mutations in the 5′UTR of the androgen receptor gene in men with prostate cancer. J Urol1997; 158: 1599. Link, Google Scholar
- 10 : Low incidence of androgen receptor gene mutations in human prostatic tumors using single strand conformation polymorphism analysis. Prostate1996; 28: 162. Google Scholar
- 11 The Androgen Receptor Gene Mutations Database. Available at. http://ww2.mcgill.ca/androgendb/. Accessed March 30, 2003. Google Scholar
- 12 : A genetic epidemiological study of hereditary prostate cancer (HPC) in Finland: frequent HPCX linkage in families with late-onset disease. Clin Cancer Res2000; 6: 4810. Google Scholar
- 13 : Androgen receptor CAG polymorphism and prostate cancer risk. Hum Genet2002; 111: 166. Google Scholar
- 14 : Mutations in the androgen receptor gene are associated with progression of human prostate cancer to androgen independence. Clin Cancer Res1996; 2: 277. Google Scholar
- 15 : Sequence of the intron/exon junctions of the coding region of the human androgen receptor gene and identification of a point mutation in a family with complete androgen insensitivity. Proc Natl Acad Sci USA1989; 86: 9534. Google Scholar
- 16 : Androgen receptor gene amplification: a possible molecular mechanism for androgen deprivation therapy failure in prostate cancer. Cancer Res1997; 57: 314. Medline, Google Scholar
- 17 : Androgen receptor gene mutations identified by SSCP in fourteen subjects with androgen insensitivity syndrome. Hum Mol Genet1992; 1: 497. Google Scholar
- 18 : Molecular characterization of the androgen receptor gene in boys with hypospadias. Eur J Pediatr1994; 153: 317. Google Scholar
- 19 : Current status of linkage studies in hereditary prostate cancer. BJU Int2000; 86: 659. Google Scholar
- 20 : Evidence for a prostate cancer susceptibility locus on the X chromosome. Nat Genet1998; 20: 175. Crossref, Medline, Google Scholar
From the Department of Clinical Genetics (PAK, E-RH), Laboratory of Cancer Genetics (PAK, MM, TI, JS), Department of Urology (MM, TLJT), Medical School (TLJT) and Institute of Medical Technology (TI, JS), University of Tampere, Tampere University Hospital, Tampere, Finland
