title: Finasteride concentrations and prostate cancer risk: results from the Prostate Cancer Prevention Trial.
abstract: OBJECTIVE
  In the Prostate Cancer Prevention Trial (PCPT), finasteride reduced the risk of prostate cancer by 25%, even though high-grade prostate cancer was more common in the finasteride group. However, it remains to be determined whether finasteride concentrations may affect prostate cancer risk. In this study, we examined the association between serum finasteride concentrations and the risk of prostate cancer in the treatment arm of the PCPT and determined factors involved in modifying drug concentrations.
  
  
  METHODS
  Data for this nested case-control study are from the PCPT. Cases were drawn from men with biopsy-proven prostate cancer and matched controls. Finasteride concentrations were measured using a liquid chromatography-mass spectrometry validated assay. The association of serum finasteride concentrations with prostate cancer risk was determined by logistic regression. We also examine whether polymorphisms in the enzyme target and metabolism genes of finasteride are related to drug concentrations using linear regression.
  
  
  CONCLUSIONS
  Among men with detectable finasteride concentrations, there was no association between finasteride concentrations and prostate cancer risk, low-grade or high-grade, when finasteride concentration was analyzed as a continuous variable or categorized by cutoff points. Since there was no concentration-dependent effect on prostate cancer, any exposure to finasteride intake may reduce prostate cancer risk. Of the twenty-seven SNPs assessed in the enzyme target and metabolism pathway, five SNPs in two genes, CYP3A4 (rs2242480; rs4646437; rs4986910), and CYP3A5 (rs15524; rs776746) were significantly associated with modifying finasteride concentrations. These results suggest that finasteride exposure may reduce prostate cancer risk and finasteride concentrations are affected by genetic variations in genes responsible for altering its metabolism pathway.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00288106.
authors.affiliation: Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Cindy H
authors.initials: CH
authors.lastname: Chau
authors.affiliation: Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Douglas K
authors.initials: DK
authors.lastname: Price
authors.affiliation: Swog Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Cathee
authors.initials: C
authors.lastname: Till
authors.affiliation: Swog Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Phyllis J
authors.initials: PJ
authors.lastname: Goodman
authors.affiliation: Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Leach
authors.affiliation: Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
authors.forename: Teresa L
authors.initials: TL
authors.lastname: Johnson-Pais
authors.affiliation: Cancer Prevention Institute of California, Fremont, California, Stanford Cancer Institute, Palo Alto, California, United States of America.
authors.forename: Ann W
authors.initials: AW
authors.lastname: Hsing
authors.affiliation: Department of Clinical Cancer Prevention, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Ashraful
authors.initials: A
authors.lastname: Hoque
authors.affiliation: Swog Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Tangen
authors.affiliation: Cancer Prevention Institute of California, Fremont, California, Stanford Cancer Institute, Palo Alto, California, United States of America.
authors.forename: Lisa
authors.initials: L
authors.lastname: Chu
authors.affiliation: Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Howard L
authors.initials: HL
authors.lastname: Parnes
authors.affiliation: Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Jeannette M
authors.initials: JM
authors.lastname: Schenk
authors.affiliation: School of Pharmacy and Molecular Sciences, James Cook University, Townsville, Queensland, Australia.
authors.forename: Juergen K V
authors.initials: JK
authors.lastname: Reichardt
authors.affiliation: Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Thompson
authors.affiliation: Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: William D
authors.initials: WD
authors.lastname: Figg
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D018120:Finasteride / Q000097:blood* / Q000627:therapeutic use*; D005820:Genetic Testing; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics / Q000517:prevention & control*
chemical_list: D018120:Finasteride; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human