Finasteride concentrations and prostate cancer risk: results from the Prostate Cancer Prevention Trial
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 st...
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| creator | 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 Figg, William D |
| description | 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.
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.
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.
ClinicalTrials.gov NCT00288106. |
| doi_str_mv | 10.1371/journal.pone.0126672 |
| format | Article |
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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.
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.
ClinicalTrials.gov NCT00288106.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0126672</identifier><identifier>PMID: 25955319</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aged ; Alcohol use ; Androgens ; Antiandrogens ; Biopsy ; Cancer ; Cardiovascular disease ; Case-Control Studies ; Chromatography ; Clinical trials ; Continuity (mathematics) ; Cytochrome P-450 ; Cytochrome P-450 CYP3A - genetics ; Disease prevention ; Enzymes ; Exposure ; Finasteride - blood ; Finasteride - therapeutic use ; Genes ; Genetic diversity ; Genetic Testing ; Haplotypes ; Health aspects ; Health risk assessment ; Health risks ; Humans ; Influence ; Liquid chromatography ; Logistic Models ; Male ; Mass spectrometry ; Mass spectroscopy ; Medical research ; Mens health ; Metabolism ; Middle Aged ; Polymorphism ; Polymorphism, Single Nucleotide ; Prevention ; Prostate ; Prostate cancer ; Prostatic Neoplasms - blood ; Prostatic Neoplasms - genetics ; Prostatic Neoplasms - prevention & control ; Quality ; Regression analysis ; Risk ; Single nucleotide polymorphisms ; Single-nucleotide polymorphism ; Urology ; Yang, Cindy</subject><ispartof>PloS one, 2015-05, Vol.10 (5), p.e0126672-e0126672</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>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: https://creativecommons.org/publicdomain/zero/1.0/ (the “License”) Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-a16dc1e5f54ee1d91b2023d5a827f707bd6595d98e75b11b10474c696dbf4f2b3</citedby><cites>FETCH-LOGICAL-c758t-a16dc1e5f54ee1d91b2023d5a827f707bd6595d98e75b11b10474c696dbf4f2b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425512/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425512/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2929,23870,27928,27929,53795,53797</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25955319$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Culig, Zoran</contributor><creatorcontrib>Chau, Cindy H</creatorcontrib><creatorcontrib>Price, Douglas K</creatorcontrib><creatorcontrib>Till, Cathee</creatorcontrib><creatorcontrib>Goodman, Phyllis J</creatorcontrib><creatorcontrib>Chen, Xiaohong</creatorcontrib><creatorcontrib>Leach, Robin J</creatorcontrib><creatorcontrib>Johnson-Pais, Teresa L</creatorcontrib><creatorcontrib>Hsing, Ann W</creatorcontrib><creatorcontrib>Hoque, Ashraful</creatorcontrib><creatorcontrib>Tangen, Catherine M</creatorcontrib><creatorcontrib>Chu, Lisa</creatorcontrib><creatorcontrib>Parnes, Howard L</creatorcontrib><creatorcontrib>Schenk, Jeannette M</creatorcontrib><creatorcontrib>Reichardt, Juergen K V</creatorcontrib><creatorcontrib>Thompson, Ian M</creatorcontrib><creatorcontrib>Figg, William D</creatorcontrib><title>Finasteride concentrations and prostate cancer risk: results from the Prostate Cancer Prevention Trial</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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.
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.
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.
ClinicalTrials.gov NCT00288106.</description><subject>Aged</subject><subject>Alcohol use</subject><subject>Androgens</subject><subject>Antiandrogens</subject><subject>Biopsy</subject><subject>Cancer</subject><subject>Cardiovascular disease</subject><subject>Case-Control Studies</subject><subject>Chromatography</subject><subject>Clinical trials</subject><subject>Continuity (mathematics)</subject><subject>Cytochrome P-450</subject><subject>Cytochrome P-450 CYP3A - genetics</subject><subject>Disease prevention</subject><subject>Enzymes</subject><subject>Exposure</subject><subject>Finasteride - blood</subject><subject>Finasteride - therapeutic use</subject><subject>Genes</subject><subject>Genetic diversity</subject><subject>Genetic Testing</subject><subject>Haplotypes</subject><subject>Health aspects</subject><subject>Health risk assessment</subject><subject>Health risks</subject><subject>Humans</subject><subject>Influence</subject><subject>Liquid chromatography</subject><subject>Logistic Models</subject><subject>Male</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Medical research</subject><subject>Mens health</subject><subject>Metabolism</subject><subject>Middle Aged</subject><subject>Polymorphism</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Prevention</subject><subject>Prostate</subject><subject>Prostate cancer</subject><subject>Prostatic Neoplasms - blood</subject><subject>Prostatic Neoplasms - genetics</subject><subject>Prostatic Neoplasms - prevention & control</subject><subject>Quality</subject><subject>Regression analysis</subject><subject>Risk</subject><subject>Single nucleotide polymorphisms</subject><subject>Single-nucleotide polymorphism</subject><subject>Urology</subject><subject>Yang, 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(mathematics)</topic><topic>Cytochrome P-450</topic><topic>Cytochrome P-450 CYP3A - genetics</topic><topic>Disease prevention</topic><topic>Enzymes</topic><topic>Exposure</topic><topic>Finasteride - blood</topic><topic>Finasteride - therapeutic use</topic><topic>Genes</topic><topic>Genetic diversity</topic><topic>Genetic Testing</topic><topic>Haplotypes</topic><topic>Health aspects</topic><topic>Health risk assessment</topic><topic>Health risks</topic><topic>Humans</topic><topic>Influence</topic><topic>Liquid chromatography</topic><topic>Logistic Models</topic><topic>Male</topic><topic>Mass spectrometry</topic><topic>Mass spectroscopy</topic><topic>Medical research</topic><topic>Mens health</topic><topic>Metabolism</topic><topic>Middle Aged</topic><topic>Polymorphism</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Prevention</topic><topic>Prostate</topic><topic>Prostate cancer</topic><topic>Prostatic Neoplasms - blood</topic><topic>Prostatic Neoplasms - 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Cathee</au><au>Goodman, Phyllis J</au><au>Chen, Xiaohong</au><au>Leach, Robin J</au><au>Johnson-Pais, Teresa L</au><au>Hsing, Ann W</au><au>Hoque, Ashraful</au><au>Tangen, Catherine M</au><au>Chu, Lisa</au><au>Parnes, Howard L</au><au>Schenk, Jeannette M</au><au>Reichardt, Juergen K V</au><au>Thompson, Ian M</au><au>Figg, William D</au><au>Culig, Zoran</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Finasteride concentrations and prostate cancer risk: results from the Prostate Cancer Prevention Trial</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-05-08</date><risdate>2015</risdate><volume>10</volume><issue>5</issue><spage>e0126672</spage><epage>e0126672</epage><pages>e0126672-e0126672</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.
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.
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.
ClinicalTrials.gov NCT00288106.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25955319</pmid><doi>10.1371/journal.pone.0126672</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015-05, Vol.10 (5), p.e0126672-e0126672 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1982585615 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Aged Alcohol use Androgens Antiandrogens Biopsy Cancer Cardiovascular disease Case-Control Studies Chromatography Clinical trials Continuity (mathematics) Cytochrome P-450 Cytochrome P-450 CYP3A - genetics Disease prevention Enzymes Exposure Finasteride - blood Finasteride - therapeutic use Genes Genetic diversity Genetic Testing Haplotypes Health aspects Health risk assessment Health risks Humans Influence Liquid chromatography Logistic Models Male Mass spectrometry Mass spectroscopy Medical research Mens health Metabolism Middle Aged Polymorphism Polymorphism, Single Nucleotide Prevention Prostate Prostate cancer Prostatic Neoplasms - blood Prostatic Neoplasms - genetics Prostatic Neoplasms - prevention & control Quality Regression analysis Risk Single nucleotide polymorphisms Single-nucleotide polymorphism Urology Yang, Cindy |
| title | Finasteride concentrations and prostate cancer risk: results from the Prostate Cancer Prevention Trial |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-16T17%3A29%3A49IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Finasteride%20concentrations%20and%20prostate%20cancer%20risk:%20results%20from%20the%20Prostate%20Cancer%20Prevention%20Trial&rft.jtitle=PloS%20one&rft.au=Chau,%20Cindy%20H&rft.date=2015-05-08&rft.volume=10&rft.issue=5&rft.spage=e0126672&rft.epage=e0126672&rft.pages=e0126672-e0126672&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0126672&rft_dat=%3Cgale_plos_%3EA431992244%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1982585615&rft_id=info:pmid/25955319&rft_galeid=A431992244&rft_doaj_id=oai_doaj_org_article_45d43f2eaad14865a539568fdd6d3918&rfr_iscdi=true |