Finasteride concentrations and prostate cancer risk: results from the Prostate Cancer Prevention Trial

Chau, Cindy H., Price, Douglas K., Till, Cathee, Goodman, Phyllis J., Chen, Xiaohong, Leach, Robin J., Johnson-Pais, Teresa L., Hsing, Ann W., Hoque, Ashraful, Tangen, Catherine M., Chu, Lisa, Parnes, Howard L., Schenk, Jeannette M., Reichardt, Juergen K.V., Thompson, Ian M., and Figg, William D. (2015) Finasteride concentrations and prostate cancer risk: results from the Prostate Cancer Prevention Trial. PLoS One, 10 (5). e0126672.

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Abstract

Objective: In the Prostate Cancer Prevention Trial (PCPT), finasteride reduced the risk of prostate cancer by 25%, even though high-grade prostate cancer was more common in the finasteride group. However, it remains to be determined whether finasteride concentrations may affect prostate cancer risk. In this study, we examined the association between serum finasteride concentrations and the risk of prostate cancer in the treatment arm of the PCPT and determined factors involved in modifying drug concentrations.

Methods: Data for this nested case-control study are from the PCPT. Cases were drawn from men with biopsy-proven prostate cancer and matched controls. Finasteride concentrations were measured using a liquid chromatography-mass spectrometry validated assay. The association of serum finasteride concentrations with prostate cancer risk was determined by logistic regression. We also examine whether polymorphisms in the enzyme target and metabolism genes of finasteride are related to drug concentrations using linear regression.

Results and Conclusions: Among men with detectable finasteride concentrations, there was no association between finasteride concentrations and prostate cancer risk, low-grade or high-grade, when finasteride concentration was analyzed as a continuous variable or categorized by cutoff points. Since there was no concentration-dependent effect on prostate cancer, any exposure to finasteride intake may reduce prostate cancer risk. Of the twenty-seven SNPs assessed in the enzyme target and metabolism pathway, five SNPs in two genes, CYP3A4 (rs2242480; rs4646437; rs4986910), and CYP3A5 (rs15524; rs776746) were significantly associated with modifying finasteride concentrations. These results suggest that finasteride exposure may reduce prostate cancer risk and finasteride concentrations are affected by genetic variations in genes responsible for altering its metabolism pathway.

Item ID: 41828
Item Type: Article (Research - C1)
ISSN: 1932-6203
Additional Information:

This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Funders: National Institutes of Health (NIH), National Cancer Institute (NCI), Center for Cancer Research, Biology of the Prostate Cancer Prevention Trial (BPCPT), Cancer Therapy and Research Center (CTRC)
Projects and Grants: NIH Intramural Research Program, BPCPT P01 CA108964, CTRC Support Grant P30 CA054174, NCI Public Health Services Grant CA37429
Date Deposited: 08 Dec 2015 18:24
FoR Codes: 06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060103 Cell Development, Proliferation and Death @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920102 Cancer and Related Disorders @ 100%
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