title: Carboxypeptidase 4 gene variants and early-onset intermediate-to-high risk prostate cancer.
abstract: BACKGROUND
  Carboxypeptidase 4 (CPA4) is a zinc-dependent metallocarboxypeptidase on chromosome 7q32 in a region linked to prostate cancer aggressiveness. CPA4 is involved in the histone hyperacetylation pathway and may modulate the function of peptides that affect the growth and regulation of prostate epithelial cells. We examined the association between genetic variation in CPA4 and intermediate-to-high risk prostate cancer.
  
  
  METHODS
  We studied 1012 men (506 cases and 506 controls) from Cleveland, Ohio. All cases had Gleason > or = 7, clinical stage > or = T2c, or PSA > or = 10 ng/mL at diagnosis. Six CPA4 single-nucleotide polymorphisms were genotyped, and evaluated for their relation to prostate cancer. We also evaluated whether CPA4 variants influence risk of disease among men diagnosed at an earlier age (< 66 years).
  
  
  RESULTS
  The nonsynonymous coding SNP (rs2171492, Cys303Gly) in CPA4 was associated with an increased risk of aggressive prostate cancer among younger patients (< 66 years). Specifically, men carrying the TT genotype had an approximately two-fold increased risk for being diagnosed with intermediate-to-high risk disease (Odds Ratio = 1.83, p = 0.04). In the overall population (all ages) none of the CPA4 SNPs demonstrated a statistically significant association with prostate cancer.
  
  
  CONCLUSIONS
  Coding variation in CPA4 may confer increased risk of intermediate-to-high risk prostate cancer among younger patients. Further work is needed to identify the functional aspects of this variation and understand its biological effects on prostate cancer. Such work may translate into more precise screening of higher risk individuals as well as guiding clinicians and patients toward earlier and more definitive treatment modalities in patients genetically identified as higher risk.
authors.affiliation: Department of Urology, University of California San Francisco, San Francisco, CA, USA. plross@usa.net
authors.forename: Phillip L
authors.initials: PL
authors.lastname: Ross
authors.forename: Iona
authors.initials: I
authors.lastname: Cheng
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Mine S
authors.initials: MS
authors.lastname: Cicek
authors.forename: Peter R
authors.initials: PR
authors.lastname: Carroll
authors.forename: Graham
authors.initials: G
authors.lastname: Casey
authors.forename: John S
authors.initials: JS
authors.lastname: Witte
mesh_terms: D001741:Black or African American; D000367:Age Factors; D000368:Aged; D002268:Carboxypeptidases / Q000235:genetics*; D043422:Carboxypeptidases A / Q000235:genetics; D042241:Early Diagnosis; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D044465:White People
chemical_list: D002268:Carboxypeptidases; C539656:CPA4, human; D043422:Carboxypeptidases A