PMID- 10606227 OWN - NLM STAT- MEDLINE DCOM- 20000106 LR - 20221207 IS - 0008-5472 (Print) IS - 0008-5472 (Linking) VI - 59 IP - 23 DP - 1999 Dec 1 TI - The V89L polymorphism in the 5alpha-reductase type 2 gene and risk of prostate cancer. PG - 5878-81 AB - 5alpha-Reductase type 2, the predominant prostatic isozyme of this protein, converts testosterone to dihydrotestosterone. It has been hypothesized that individuals with greater 5alpha-reductase activity are at increased risk for prostate cancer (CaP). A single nucleotide polymorphism of the 5alpha-reductase type 2 gene (SRD5A2) gives rise to a substitution of leucine (leu) for valine (val) at codon 89 (V89L), the presence of which may affect serum androstanediol glucuronide (AAG) levels. We studied the effect of this polymorphism on the risk of prostate cancer in a prospective, nested, case-control design within the Physicians' Health Study. In all controls (n = 799), the leu allele frequency was 0.30. Among the 386 controls with plasma AAG levels available, there was no significant association between AAG levels and V89L genotype. We also detected no significant association between risk for CaP and genotype [odds ratio: val/val = 1.0 (reference), leu/val = 0.96 (95% confidence interval, 0.76-1.20), and leu/ leu = 0.84 (95% confidence interval, 0.57-1.24)]. These data do not support a moderate to large effect of the SRD5A2 V89L polymorphism on plasma AAG levels or CaP risk in this predominantly Caucasian cohort, although a small effect cannot be completely excluded. FAU - Febbo, P G AU - Febbo PG AD - Department of Adult Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA. FAU - Kantoff, P W AU - Kantoff PW FAU - Platz, E A AU - Platz EA FAU - Casey, D AU - Casey D FAU - Batter, S AU - Batter S FAU - Giovannucci, E AU - Giovannucci E FAU - Hennekens, C H AU - Hennekens CH FAU - Stampfer, M J AU - Stampfer MJ LA - eng GR - CA42182/CA/NCI NIH HHS/United States GR - CA58684/CA/NCI NIH HHS/United States GR - CA72036/CA/NCI NIH HHS/United States PT - Clinical Trial PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Cancer Res JT - Cancer research JID - 2984705R RN - 0 (Anticarcinogenic Agents) RN - 0 (Isoenzymes) RN - 01YAE03M7J (beta Carotene) RN - EC 1.3.99.5 (3-Oxo-5-alpha-Steroid 4-Dehydrogenase) RN - GMW67QNF9C (Leucine) RN - HG18B9YRS7 (Valine) RN - R16CO5Y76E (Aspirin) SB - IM MH - 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/*genetics MH - Adult MH - Aged MH - Aged, 80 and over MH - Amino Acid Substitution MH - Anticarcinogenic Agents/therapeutic use MH - Aspirin/therapeutic use MH - Boston/epidemiology MH - Double-Blind Method MH - Heart Diseases/prevention & control MH - Humans MH - Isoenzymes/genetics MH - Leucine MH - Male MH - Middle Aged MH - Neoplasms/prevention & control MH - *Polymorphism, Genetic MH - Prostatic Neoplasms/*epidemiology/*genetics MH - Risk Factors MH - Valine MH - White People MH - beta Carotene/therapeutic use EDAT- 1999/12/22 00:00 MHDA- 1999/12/22 00:01 CRDT- 1999/12/22 00:00 PHST- 1999/12/22 00:00 [pubmed] PHST- 1999/12/22 00:01 [medline] PHST- 1999/12/22 00:00 [entrez] PST - ppublish SO - Cancer Res. 1999 Dec 1;59(23):5878-81.