title: A prevalent missense substitution that modulates activity of prostatic steroid 5alpha-reductase.
abstract: Prostate cancer is the most common serious cancer diagnosed in men in the United States. This disease is also characterized by a striking racial/ethnic variation in incidence: highest in African-Americans, intermediate in Caucasians, slightly lower in Latinos, and lowest in Asians. Ample biochemical and epidemiological evidence suggests a role for androgens, particularly testosterone and dihydrotestosterone, in prostate cancer etiology. We have analyzed a candidate gene for prostate cancer, SRD5A2, encoding prostatic steroid 5alpha-reductase type II, which converts testosterone into the more bioactive dihydrotestosterone, for mutations. We report here one amino acid substitution, V89L, which replaces valine at codon 89 with leucine. This substitution is a "germline" (constitutional) DNA polymorphism, and it is common, panethnic, and reduces in vivo steroid 5alpha-reductase activity. This substitution is particularly common among Asians and may explain the low risk for prostate cancer in this population.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern California School of Medicine, USC/Norris Comprehensive Cancer Center, Los Angeles 90033-1034, USA.
authors.forename: N
authors.initials: N
authors.lastname: Makridakis
authors.forename: R K
authors.initials: RK
authors.lastname: Ross
authors.forename: M C
authors.initials: MC
authors.lastname: Pike
authors.forename: L
authors.initials: L
authors.lastname: Chang
authors.forename: F Z
authors.initials: FZ
authors.lastname: Stanczyk
authors.forename: L N
authors.initials: LN
authors.lastname: Kolonel
authors.forename: C Y
authors.initials: CY
authors.lastname: Shi
authors.forename: M C
authors.initials: MC
authors.lastname: Yu
authors.forename: B E
authors.initials: BE
authors.lastname: Henderson
authors.forename: J K
authors.initials: JK
authors.lastname: Reichardt
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics* / Q000502:physiology; D000483:Alleles; D003062:Codon / Q000235:genetics; D015331:Cohort Studies; D013196:Dihydrotestosterone / Q000378:metabolism; D004198:Disease Susceptibility; D005787:Gene Frequency; D006801:Humans; D008297:Male; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000208:ethnology / Q000235:genetics; D044469:Racial Groups / Q000235:genetics
chemical_list: D003062:Codon; D013196:Dihydrotestosterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase