Short tandem repeat polymorphism linkage to the androgen receptor gene in prostate carcinoma.
BACKGROUND
Due to high polymorphism, common sequences, and ubiquitous presence, short tandem repeats (STRs) may enhance genomic typing to determine prostate carcinoma (CaP) predisposition. The human phosphoglycerate kinase (PGK1) gene is located within Xq11-Xq13, a region implicated in familial prostate carcinoma, androgen insensitivity, perineal hypospadias, and other genitourinary abnormalities. The PGK1 STR is the most polymorphic site described in the Xq11-Xq13 interval and was investigated for its ability to detect differences comparing a heterogeneous CaP population versus controls.


METHODS
We compared PGK1 STR allele sizes in 103 localized CaP patients with 299 control subjects to evaluate the STR's ability to detect potential CaP predisposing genetic factors. Allele sizes were measured with an automated DNA sequencer after polymerase chain reaction (PCR) based copying of the PGK1 STR region. Allele sizes were compared using chi square and Mann-Whitney U tests.


RESULTS
Among 402 subjects, there were 10 distinct allele sizes consisting of five common and five relatively rare alleles. The PGK1 STR, 12 allele (12 tetrameric repeats) was more common among patients with CaP (p=0.03). Allele 13 was more common in CaP patients > 60 years old than among younger patients (p< 0.005).


CONCLUSIONS
Our findings suggest that STRs in the Xq11-Xq13 region and other regions may provide a means to rapidly scan genetic loci in large populations of CaP patients and controls. Within limitations, STRs offer the advantage of relatively uniform protocols that could potentially provide a means to comprehensively scan genomes at known predisposing loci.
Riley
D E
DE
Department of Veteran Affairs, Seattle, WA 98108-1597, USA. dri@u.washington.edu
Krieger
J N
JN
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D004273:DNA, Neoplasm / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D010735:Phosphoglycerate Kinase / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011944:Receptors, Androgen / Q000235:genetics*; D020080:Tandem Repeat Sequences / Q000235:genetics*; D014960:X Chromosome / Q000235:genetics
D004273:DNA, Neoplasm; D011944:Receptors, Androgen; D010735:Phosphoglycerate Kinase