Abstract | PURPOSE: METHODS: 3048 male participants of The Rotterdam Study were included. Prostate cancer cases and non-cases were studied for differences in baseline hormone levels with Student's t-test. General linear models were performed on different random subsets of hormone levels to study associations with genotype. Cox' proportional hazard models were used to study prostate cancer incidence and mortality among genotypes. RESULTS: Both DHEAS sulphate as free- testosterone were significantly increased at baseline in males who developed a prostate cancer within the study period. CYP3A4 G-allele carriage was associated with lower levels of estrone sulphate (p=0.005) and higher levels of estradiol (p=0.04) compared to non-carriers. CYP3A5 A-allele carriage was associated with increased levels of estrone sulphate (p=0.02). CYP3A7 G-allele carriage was associated with the highest number of significant differences in steroid hormone levels. Carriers of the allele resulting in continued enzyme expression during adulthood had decreased levels of dehydroepiandrosterone ( DHEA) sulphate (p=0.05), androstenedione (p=0.006), estrone (p=0.0001) and estrone sulphate (p=0.003) compared to mean levels of these hormones in homozygous wild type carriers. CYP3A43 genotype was not associated with any of the studied hormone levels. However, carriers of the CYP3A43 G-allele showed a significant 5-fold increase in mortality among early onset diagnosed prostate cancers. CONCLUSION:
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Authors | Claire Siemes, Loes E Visser, Frank H de Jong, Jan-Willem W Coebergh, André G Uitterlinden, Albert Hofman, Bruno H Ch Stricker, Ron H N van Schaik |
Journal | Steroids
(Steroids)
Vol. 75
Issue 12
Pg. 1024-32
(Dec 2010)
ISSN: 1878-5867 [Electronic] United States |
PMID | 20621111
(Publication Type: Journal Article)
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Copyright | Copyright 2010 Elsevier Inc. All rights reserved. |
Chemical References |
- Hormones
- Steroids
- Cytochrome P-450 CYP3A
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Topics |
- Aged
- Cohort Studies
- Cytochrome P-450 CYP3A
(genetics)
- Gene Expression Regulation, Neoplastic
- Hormones
(blood)
- Humans
- Male
- Middle Aged
- Netherlands
- Polymorphism, Single Nucleotide
- Prostatic Neoplasms
(blood, epidemiology, genetics)
- Steroids
(blood)
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