Association between polymorphisms in HSD3B1 and UGT2B17 and prostate cancer risk.
OBJECTIVE
Androgens, especially dihydrotestosterone, have been postulated to modify the risk of prostate cancer. 3-Beta-hydroxysteroid dehydrogenase1 (HSD3B1) and uridine diphosphate-glucuronosyltransferase 2B17 (UGT2B17) are enzymes that inactivate dihydrotestosterone in the prostate and may affect dihydrotestosterone concentration in prostatic tissue. The purpose of this study was to determine whether polymorphisms in HSD3B1 and UGT2B17 increase the risk of prostate cancer.


METHODS
In a case-control study of 356 patients with incident primary prostate cancer and 363 age-matched controls, the frequencies of HSD3B1 N367T and UGT2B17 null polymorphisms in genomic DNA were compared between the patients and controls.


RESULTS
No evidence was found for a main effect of the HSD3B1 codon 367 polymorphism on prostate cancer risk. However, among white men with family history of prostate cancer, the HSD3B1 367Thr allele was positively associated with prostate cancer (odds ratio 3.0, 95% confidence interval 1.0 to 9.2). A significant association was observed between the UGT2B17 null polymorphism and prostate cancer risk (odds ratio 1.7, 95% confidence interval 1.03 to 2.9). An association with the UGT2B17 null polymorphism was further elevated (odds ratio 2.7, 95% confidence interval 1.1 to 6.5) among individuals with HSD3B1 Asn/Asn genotype.


CONCLUSIONS
These results suggest that the HSD3B1 N367T and UGT2B17 null polymorphisms may modify the risk of prostate cancer, particularly among men with a family history of the disease.
Park
Jong Y
JY
Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA. jong.park@moffitt.org
Tanner
Jean-Paul
JP
Sellers
Thomas A
TA
Huang
Yifan
Y
Stevens
Colleen K
CK
Dossett
Nicole
N
Shankar
Ravi A
RA
Zachariah
Babu
B
Heysek
Randy
R
Pow-Sang
Julio
J
D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics*; D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D008297:Male; D015778:Minor Histocompatibility Antigens; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D012307:Risk Factors