Combination of polymorphisms from genes related to estrogen metabolism and risk of prostate cancers: the hidden face of estrogens.
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.
Cussenot
Olivier
O
Centre de Recherche pour les Pathologies Prostatiques, Tenon Hospital, Paris, France. olivier.cussenot@tnn.aphp.fr
Azzouzi
Abdel Rhamene
AR
Nicolaiew
Nathalie
N
Fromont
Gaelle
G
Mangin
Philippe
P
Cormier
Luc
L
Fournier
Georges
G
Valeri
Antoine
A
Larre
Stephane
S
Thibault
Frederic
F
Giordanella
Jean-Pierre
JP
Pouchard
Michel
M
Zheng
Yan
Y
Hamdy
Freddie C
FC
Cox
Angela
A
Cancel-Tassin
Geraldine
G
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
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