title: Combination of polymorphisms from genes related to estrogen metabolism and risk of prostate cancers: the hidden face of estrogens.
abstract: OBJECTIVE
  The association between common functional polymorphisms from the CYP17, CYP19, CYP1B1, and COMT genes involved in the estrogen metabolism and the risk of prostate carcinoma was evaluated.
  
  
  METHODS
  The study investigated 1,983 white French men (1,101 patients with prostate cancer and 882 healthy controls) aged between 40 and 98 years. The different alleles and genotypes were analyzed according to case-control status, aggressiveness pattern of the tumors, age at onset, and family history of cancers.
  
  
  RESULTS
  The VV (high activity) genotype of the V432L polymorphism from CYP1B1 (odds ratio [OR] = 1.36; 95% CI, 1.03 to 1.79; P = .031), and the long allele (> 175 bp) of the TTTA repeat from CYP19 (OR, 1.26; 95% CI, 1.08 to 1.47; P = .003) were significantly associated with the risk of prostate cancer. An additive effect was observed when we combined the two at-risk alleles (OR = 1.63; 95% CI, 1.24 to 2.13; P < .001). The association was stronger for the CYP1B1 VV genotype (OR = 1.55; 95% CI, 1.13 to 2.13; P = .007) among the group of patients with highly aggressive disease. Stratification by age at onset showed that the associations of CYP1B1 and CYP19 variants were largely confined to the younger prostate cancer patients.
  
  
  CONCLUSIONS
  This association between polymorphisms from genes related to estrogen metabolism and prostate cancer risk suggest new clinical considerations in the management of prostate cancer: the development of new prevention trials based on genetic profiling and the evaluation of specific inhibitors involving the estrogen pathways.
authors: Centre de Recherche pour les Pathologies Prostatiques, Tenon Hospital, Paris, France. olivier.cussenot@tnn.aphp.fr
authors: Olivier
authors: O
authors: Cussenot
authors: Abdel Rhamene
authors: AR
authors: Azzouzi
authors: Nathalie
authors: N
authors: Nicolaiew
authors: Gaelle
authors: G
authors: Fromont
authors: Philippe
authors: P
authors: Mangin
authors: Luc
authors: L
authors: Cormier
authors: Georges
authors: G
authors: Fournier
authors: Antoine
authors: A
authors: Valeri
authors: Stephane
authors: S
authors: Larre
authors: Frederic
authors: F
authors: Thibault
authors: Jean-Pierre
authors: JP
authors: Giordanella
authors: Michel
authors: M
authors: Pouchard
authors: Yan
authors: Y
authors: Zheng
authors: Freddie C
authors: FC
authors: Hamdy
authors: Angela
authors: A
authors: Cox
authors: Geraldine
authors: G
authors: Cancel-Tassin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001141:Aromatase / Q000235:genetics; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D002394:Catechol O-Methyltransferase / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1; D004967:Estrogens / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics*; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics
chemical_list: D004967:Estrogens; D001141:Aromatase; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1; D013254:Steroid 17-alpha-Hydroxylase; D002394:Catechol O-Methyltransferase