title: Androgen metabolism and JAK/STAT pathway genes and prostate cancer risk.
abstract: BACKGROUND
  Prostate cancer (PC) is the most frequently diagnosed solid tumor in U.S. men. Genome-wide association studies (GWAS) have identified over 40 risk-associated single nucleotide polymorphisms (SNPs), including variants in androgen pathway genes (e.g., KLK3 and AR). Androgens are important in PC and genes involved in this pathway are therefore candidates for conferring susceptibility to PC.
  
  
  METHODS
  In this hypothesis-testing study, we evaluated PC risk in association with SNPs in 22 candidate genes involved in androgen metabolism or interactions with the androgen receptor (AR). A total of 187 SNPs were genotyped in 1458 cases and 1351 age-matched controls from a population-based study. PC risk was estimated using adjusted unconditional logistic regression and multinomial regression models.
  
  
  RESULTS
  Single SNP analyses showed evidence (p < 0.05) for associations with 14 SNPs in 9 genes: NKX3.1, HSD17B3, AKR1C3, SULT2A1, CYP17A1, KLK3, JAK2, NCOA4 and STAT3. The most significant result was observed for rs2253502 in HSD17B3 (odds ratio, OR = 0.57, 95% CI: 0.39-0.84). In addition, five SNPs in four genes (CYP17A1, HSD17B4, NCOA4, and SULT2A1) were associated with more aggressive disease (p < 0.01).
  
  
  CONCLUSIONS
  Our results replicate previously reported associations for SNPs in CYP17A1, HSD17B3, ARK1C3, NKX3.1, NCOA4 and KLK3. In addition, novel associations were observed for SNPs in JAK2, HSD17B4, and SULT2A1. These results will require replication in larger studies.
authors.affiliation: National Human Genome Research Institute, Cancer Genetics Branch, National Institutes of Health, Building 50, 50 South Drive, Bethesda, MD 20892, USA. kwone@mail.nih.gov
authors.forename: Erika M
authors.initials: EM
authors.lastname: Kwon
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Holt
authors.forename: Rong
authors.initials: R
authors.lastname: Fu
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kolb
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Williams
authors.forename: Janet L
authors.initials: JL
authors.lastname: Stanford
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Ostrander
mesh_terms: D000328:Adult; D001741:Black or African American; D000368:Aged; D000728:Androgens / Q000378:metabolism*; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D044465:White People
chemical_list: D000728:Androgens; D011944:Receptors, Androgen; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2