Association between hormonal genetic polymorphisms and early-onset prostate cancer.
We investigated the association between seven polymorphisms in four candidate genes involved in vitamin D and androgen metabolism with early-onset prostate cancer (CaP) risk. The polymorphisms were genotyped in 288 UK males who were diagnosed with CaP at the age of 55 y or younger and up to 700 population-based controls. An additional 50 cases (not selected for age) and 76 controls were also genotyped. Short (< or =22 repeats) AR (CAG)(n) repeats were associated with a significantly reduced risk of early onset CaP (OR 0.68, 95% CI 0.50-0.91) compared with men with long (> 22) repeats. Men homozygous for the leucine variant of SRD5A2 p.89V > L were also found to be at a significantly increased risk of CaP compared with men who were homozygous for the valine allele (OR 1.84, 95% CI 1.15-2.98). No associations were found with the AR (GGC)(n), CYP17 Msp A1 I, VDR Taq I, SRD5A2 (TA)(n) and p.49A >T polymorphisms and CaP risk. These findings suggest that common polymorphisms in the AR and SRD5A2 genes may be associated with early-onset CaP in British men.
Forrest
M S
MS
Cancer Research UK Cancer Medicine Research Division, University of Leeds, Leeds, UK.
Edwards
S M
SM
Houlston
R
R
Kote-Jarai
Z
Z
Key
T
T
Allen
N
N
Knowles
M A
MA
Turner
F
F
Ardern-Jones
A
A
Murkin
A
A
Williams
S
S
Oram
R
R
Bishop
D T
DT
Eeles
R A
RA
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics*; D000328:Adult; D017668:Age of Onset; D000728:Androgens / Q000378:metabolism; D000975:Antioxidants / Q000378:metabolism; D016022:Case-Control Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D011944:Receptors, Androgen / Q000235:genetics*; D018911:Trinucleotide Repeats; D006113:United Kingdom; D014807:Vitamin D / Q000378:metabolism
D000728:Androgens; D000975:Antioxidants; D011944:Receptors, Androgen; D014807:Vitamin D; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase