Deletion polymorphism of the UGT2B17 gene is associated with increased risk for prostate cancer and correlated to gene expression in the prostate.
Metabolism of androgens includes glucuronidation, the major pathway of steroid elimination in several steroid target tissues. Glucuronidation is catalysed by UDP-glucuronosyltransferases (UGTs). UGT2B17 has been shown to be particularly active against androgens and is highly abundant in the prostate. Recently, we discovered that deletion of the UGT2B17 gene is associated with low or undetectable urinary testosterone levels. Here, we determined the phenotypic outcome of the deletion by quantifying the UGT2B17 mRNA expression in normal prostate tissues in individuals with different genotypes. Additionally, the frequency of UGT2B17 deletion polymorphism was studied in a Swedish population-based case-control study including 176 patients diagnosed with prostate cancer and 161 controls. We found that the individuals homozygous for the insertion allele expressed 30 times more UGT2B17 mRNA in prostate tissue than the heterozygotes. Carriers of the deletion allele had a significantly increased risk of prostate cancer (OR=2.07; 95% CI=1.32-3.25). In conclusion, these results show the UGT2B17 deletion polymorphism is associated with prostate cancer risk.
Karypidis
A-H
AH
Department of Laboratory Medicine, Division of Clinical Pharmacology at Karolinska Institutet, Stockholm, Sweden.
Olsson
M
M
Andersson
S-O
SO
Rane
A
A
Ekström
L
L
D000368:Aged; D000728:Androgens / Q000378:metabolism; D016022:Case-Control Studies; D017353:Gene Deletion; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014453:Glucuronosyltransferase / Q000032:analysis / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D016017:Odds Ratio; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011467:Prostate / Q000201:enzymology*; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D018570:Risk Assessment; D012307:Risk Factors; D013548:Sweden; D015854:Up-Regulation
D000728:Androgens; D015778:Minor Histocompatibility Antigens; D012333:RNA, Messenger; D014453:Glucuronosyltransferase; C500513:UGT2B17 protein, human