title: Novel associations of UDP-glucuronosyltransferase 2B gene variants with prostate cancer risk in a multiethnic study.
abstract: BACKGROUND
  We have previously shown that a functional polymorphism of the UGT2B15 gene (rs1902023) was associated with increased risk of prostate cancer (PC). Novel functional polymorphisms of the UGT2B17 and UGT2B15 genes have been recently characterized by in vitro assays but have not been evaluated in epidemiologic studies.
  
  
  METHODS
  Fifteen functional SNPs of the UGT2B17 and UGT2B15 genes, including cis-acting UGT2B gene SNPs, were genotyped in African American and Caucasian men (233 PC cases and 342 controls). Regression models were used to analyze the association between SNPs and PC risk.
  
  
  RESULTS
  After adjusting for race, age and BMI, we found that six UGT2B15 SNPs (rs4148269, rs3100, rs9994887, rs13112099, rs7686914 and rs7696472) were associated with an increased risk of PC in log-additive models (p < 0.05). A SNP cis-acting on UGT2B17 and UGT2B15 expression (rs17147338) was also associated with increased risk of prostate cancer (OR = 1.65, 95% CI = 1.00-2.70); while a stronger association among men with high Gleason sum was observed for SNPs rs4148269 and rs3100.
  
  
  CONCLUSIONS
  Although small sample size limits inference, we report novel associations between UGT2B15 and UGT2B17 variants and PC risk. These associations with PC risk in men with high Gleason sum, more frequently found in African American men, support the relevance of genetic differences in the androgen metabolism pathway, which could explain, in part, the high incidence of PC among African American men. Larger studies are required.
authors.affiliation: Department of Biology and Cancer Research Program, JLC-Biomedical/Biotechnology Research Institute, North Carolina Central University, Durham, NC 27707, USA. dgrant@nccu.edu.
authors.forename: Adriana C
authors.initials: AC
authors.lastname: Vidal
authors.forename: Cocoa
authors.initials: C
authors.lastname: Tucker
authors.forename: Joellen M
authors.initials: JM
authors.lastname: Schildkraut
authors.forename: Ricardo M
authors.initials: RM
authors.lastname: Richardson
authors.forename: Megan
authors.initials: M
authors.lastname: McPhail
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Freedland
authors.forename: Cathrine
authors.initials: C
authors.lastname: Hoyo
authors.forename: Delores J
authors.initials: DJ
authors.lastname: Grant
mesh_terms: D001741:Black or African American / Q000235:genetics; D000368:Aged; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000208:ethnology / Q000235:genetics*; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D044465:White People / Q000235:genetics
chemical_list: D015778:Minor Histocompatibility Antigens; D014453:Glucuronosyltransferase; C472000:UDP-glucuronosyltransferase 2B15, human; C500513:UGT2B17 protein, human