title: Decision tree-based modeling of androgen pathway genes and prostate cancer risk.
abstract: BACKGROUND
  Inherited variability in genes that influence androgen metabolism has been associated with risk of prostate cancer. The objective of this analysis was to evaluate interactions for prostate cancer risk by using classification and regression tree (CART) models (i.e., decision trees), and to evaluate whether these interactive effects add information about prostate cancer risk prediction beyond that of "traditional" risk factors.
  
  
  METHODS
  We compared CART models with traditional logistic regression (LR) models for associations of factors with prostate cancer risk using 1,084 prostate cancer cases and 941 controls. All analyses were stratified by race. We used unconditional LR to complement and compare with the race-stratified CART results using the area under curve (AUC) for the receiver operating characteristic curves.
  
  
  RESULTS
  The CART modeling of prostate cancer risk showed different interaction profiles by race. For European Americans, interactions among CYP3A43 genotype, history of benign prostate hypertrophy, family history of prostate cancer, and age at consent revealed a distinct hierarchy of gene-environment and gene-gene interactions, whereas for African Americans, interactions among family history of prostate cancer, individual proportion of European ancestry, number of GGC androgen receptor repeats, and CYP3A4/CYP3A5 haplotype revealed distinct interaction effects from those found in European Americans. For European Americans, the CART model had the highest AUC whereas for African Americans, the LR model with the CART discovered factors had the largest AUC.
  
  
  CONCLUSIONS
  These results provide new insight into underlying prostate cancer biology for European Americans and African Americans.
authors.affiliation: Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106-5065, USA. jsb42@case.edu
authors.forename: Jill S
authors.initials: JS
authors.lastname: Barnholtz-Sloan
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Guan
authors.forename: Charnita
authors.initials: C
authors.lastname: Zeigler-Johnson
authors.forename: Neal J
authors.initials: NJ
authors.lastname: Meropol
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Rebbeck
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics; D000328:Adult; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D016022:Case-Control Studies; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D004247:DNA / Q000235:genetics; D003661:Decision Support Techniques; D003663:Decision Trees; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011467:Prostate / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics*; D012372:ROC Curve; D011944:Receptors, Androgen / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D012307:Risk Factors
chemical_list: C410798:AR protein, human; D008565:Membrane Proteins; D011944:Receptors, Androgen; D004247:DNA; D001189:Aryl Hydrocarbon Hydroxylases; C422408:CYP3A43 protein, human; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C548468:SRD5A2 protein, human