Efficacy of tamoxifen based on cytochrome P450 2D6, CYP2C19 and SULT1A1 genotype in the Italian Tamoxifen Prevention Trial
The role of pharmacogenomics and tamoxifen was investigated by analyzing several polymorphisms of cytochrome P450 and SULT1A1 gene in a nested case control study from the Italian Tamoxifen Prevention Trial. This study included 182 Caucasian subjects, 47 breast cancer (BC) cases and 135 matched contr...
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| Veröffentlicht in: | The pharmacogenomics journal 2011-04, Vol.11 (2), p.100-107 |
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| creator | Serrano, D Lazzeroni, M Zambon, C-F Macis, D Maisonneuve, P Johansson, H Guerrieri-Gonzaga, A Plebani, M Basso, D Gjerde, J Mellgren, G Rotmensz, N Decensi, A Bonanni, B |
| description | The role of pharmacogenomics and tamoxifen was investigated by analyzing several polymorphisms of cytochrome P450 and SULT1A1 gene in a nested case control study from the Italian Tamoxifen Prevention Trial. This study included 182 Caucasian subjects, 47 breast cancer (BC) cases and 135 matched controls. We used the AmpliChip CYP450 Test to screen 33 alleles of CYP2D6 and 3 of CYP2C19. One more variant for CYP2C19
*
17 and two single-nucleotide polymorphisms for the gene
SULT1A1
were also performed. By using the AmpliChip CYP450 Test, out of 182 subjects, we identified 8 poor metabolizer (PM), 17 intermediate metabolizer (IM), 151 extensive metabolizer (EM) and 3 ultrarapid metabolizer (UM). PM women allocated to the tamoxifen arm showed a higher risk of developing BC compared to the remaining phenotypes (
P
=0.035). In an exploratory analysis, among 58 women with a CYP2D6
*
2A allele, 9 BCs were diagnosed in the placebo arm and only 1 in the tamoxifen arm (
P
=0.0001). CYP2C19 and SULT1A1 polymorphisms did not show any correlation with tamoxifen efficacy. Tamoxifen showed reduced efficacy in CYP2D6 PMs in the chemoprevention setting. Conversely, the CYP2D6
*
2A allele may be associated with increased efficacy of tamoxifen. These findings support the relevance of pharmaco-genomics in tailoring tamoxifen treatment. |
| doi_str_mv | 10.1038/tpj.2010.17 |
| format | Article |
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*
17 and two single-nucleotide polymorphisms for the gene
SULT1A1
were also performed. By using the AmpliChip CYP450 Test, out of 182 subjects, we identified 8 poor metabolizer (PM), 17 intermediate metabolizer (IM), 151 extensive metabolizer (EM) and 3 ultrarapid metabolizer (UM). PM women allocated to the tamoxifen arm showed a higher risk of developing BC compared to the remaining phenotypes (
P
=0.035). In an exploratory analysis, among 58 women with a CYP2D6
*
2A allele, 9 BCs were diagnosed in the placebo arm and only 1 in the tamoxifen arm (
P
=0.0001). CYP2C19 and SULT1A1 polymorphisms did not show any correlation with tamoxifen efficacy. Tamoxifen showed reduced efficacy in CYP2D6 PMs in the chemoprevention setting. Conversely, the CYP2D6
*
2A allele may be associated with increased efficacy of tamoxifen. These findings support the relevance of pharmaco-genomics in tailoring tamoxifen treatment.</description><identifier>ISSN: 1470-269X</identifier><identifier>EISSN: 1473-1150</identifier><identifier>DOI: 10.1038/tpj.2010.17</identifier><identifier>PMID: 20309015</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/92/436/108 ; 692/699/67/1347 ; 692/699/67/1857 ; 692/700/565/1436/434 ; Alleles ; Antineoplastic Agents, Hormonal - therapeutic use ; Aryl Hydrocarbon Hydroxylases - genetics ; Arylsulfotransferase - genetics ; Biomedical and Life Sciences ; Biomedicine ; Breast cancer ; Breast Neoplasms - prevention & control ; Care and treatment ; Case-Control Studies ; Clinical Trials as Topic ; Complications and side effects ; CYP2D6 protein ; Cytochrome ; Cytochrome P-450 ; Cytochrome P-450 CYP2C19 ; Cytochrome P-450 CYP2D6 - genetics ; Cytochrome P450 ; Drug Resistance, Neoplasm - genetics ; Female ; Gene Expression ; Health aspects ; Human Genetics ; Humans ; Italy ; Middle Aged ; Oncology ; original-article ; Pharmacogenomics ; Pharmacotherapy ; Phenotypes ; Polymorphism, Single Nucleotide ; Prevention ; Psychopharmacology ; Risk factors ; Single nucleotide polymorphisms ; Single-nucleotide polymorphism ; Tamoxifen ; Tamoxifen - therapeutic use ; Treatment Outcome</subject><ispartof>The pharmacogenomics journal, 2011-04, Vol.11 (2), p.100-107</ispartof><rights>Macmillan Publishers Limited 2011</rights><rights>COPYRIGHT 2011 Nature Publishing Group</rights><rights>Macmillan Publishers Limited 2011.</rights><rights>Copyright Nature Publishing Group Apr 2011</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c506t-4d57eb6e8d230295e8f87a56c094856837ecbe52da7a0a9f022230cbb0719c533</citedby><cites>FETCH-LOGICAL-c506t-4d57eb6e8d230295e8f87a56c094856837ecbe52da7a0a9f022230cbb0719c533</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20309015$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Serrano, D</creatorcontrib><creatorcontrib>Lazzeroni, M</creatorcontrib><creatorcontrib>Zambon, C-F</creatorcontrib><creatorcontrib>Macis, D</creatorcontrib><creatorcontrib>Maisonneuve, P</creatorcontrib><creatorcontrib>Johansson, H</creatorcontrib><creatorcontrib>Guerrieri-Gonzaga, A</creatorcontrib><creatorcontrib>Plebani, M</creatorcontrib><creatorcontrib>Basso, D</creatorcontrib><creatorcontrib>Gjerde, J</creatorcontrib><creatorcontrib>Mellgren, G</creatorcontrib><creatorcontrib>Rotmensz, N</creatorcontrib><creatorcontrib>Decensi, A</creatorcontrib><creatorcontrib>Bonanni, B</creatorcontrib><title>Efficacy of tamoxifen based on cytochrome P450 2D6, CYP2C19 and SULT1A1 genotype in the Italian Tamoxifen Prevention Trial</title><title>The pharmacogenomics journal</title><addtitle>Pharmacogenomics J</addtitle><addtitle>Pharmacogenomics J</addtitle><description>The role of pharmacogenomics and tamoxifen was investigated by analyzing several polymorphisms of cytochrome P450 and SULT1A1 gene in a nested case control study from the Italian Tamoxifen Prevention Trial. This study included 182 Caucasian subjects, 47 breast cancer (BC) cases and 135 matched controls. We used the AmpliChip CYP450 Test to screen 33 alleles of CYP2D6 and 3 of CYP2C19. One more variant for CYP2C19
*
17 and two single-nucleotide polymorphisms for the gene
SULT1A1
were also performed. By using the AmpliChip CYP450 Test, out of 182 subjects, we identified 8 poor metabolizer (PM), 17 intermediate metabolizer (IM), 151 extensive metabolizer (EM) and 3 ultrarapid metabolizer (UM). PM women allocated to the tamoxifen arm showed a higher risk of developing BC compared to the remaining phenotypes (
P
=0.035). In an exploratory analysis, among 58 women with a CYP2D6
*
2A allele, 9 BCs were diagnosed in the placebo arm and only 1 in the tamoxifen arm (
P
=0.0001). CYP2C19 and SULT1A1 polymorphisms did not show any correlation with tamoxifen efficacy. Tamoxifen showed reduced efficacy in CYP2D6 PMs in the chemoprevention setting. Conversely, the CYP2D6
*
2A allele may be associated with increased efficacy of tamoxifen. These findings support the relevance of pharmaco-genomics in tailoring tamoxifen treatment.</description><subject>631/92/436/108</subject><subject>692/699/67/1347</subject><subject>692/699/67/1857</subject><subject>692/700/565/1436/434</subject><subject>Alleles</subject><subject>Antineoplastic Agents, Hormonal - therapeutic use</subject><subject>Aryl Hydrocarbon Hydroxylases - genetics</subject><subject>Arylsulfotransferase - genetics</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - prevention & control</subject><subject>Care and treatment</subject><subject>Case-Control Studies</subject><subject>Clinical Trials as Topic</subject><subject>Complications and side effects</subject><subject>CYP2D6 protein</subject><subject>Cytochrome</subject><subject>Cytochrome P-450</subject><subject>Cytochrome P-450 CYP2C19</subject><subject>Cytochrome P-450 CYP2D6 - genetics</subject><subject>Cytochrome P450</subject><subject>Drug Resistance, Neoplasm - 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therapeutic use</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Serrano, D</creatorcontrib><creatorcontrib>Lazzeroni, M</creatorcontrib><creatorcontrib>Zambon, C-F</creatorcontrib><creatorcontrib>Macis, D</creatorcontrib><creatorcontrib>Maisonneuve, P</creatorcontrib><creatorcontrib>Johansson, H</creatorcontrib><creatorcontrib>Guerrieri-Gonzaga, A</creatorcontrib><creatorcontrib>Plebani, M</creatorcontrib><creatorcontrib>Basso, D</creatorcontrib><creatorcontrib>Gjerde, J</creatorcontrib><creatorcontrib>Mellgren, G</creatorcontrib><creatorcontrib>Rotmensz, N</creatorcontrib><creatorcontrib>Decensi, A</creatorcontrib><creatorcontrib>Bonanni, B</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection (ProQuest)</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The pharmacogenomics journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Serrano, D</au><au>Lazzeroni, M</au><au>Zambon, C-F</au><au>Macis, D</au><au>Maisonneuve, P</au><au>Johansson, H</au><au>Guerrieri-Gonzaga, A</au><au>Plebani, M</au><au>Basso, D</au><au>Gjerde, J</au><au>Mellgren, G</au><au>Rotmensz, N</au><au>Decensi, A</au><au>Bonanni, B</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy of tamoxifen based on cytochrome P450 2D6, CYP2C19 and SULT1A1 genotype in the Italian Tamoxifen Prevention Trial</atitle><jtitle>The pharmacogenomics journal</jtitle><stitle>Pharmacogenomics J</stitle><addtitle>Pharmacogenomics J</addtitle><date>2011-04-01</date><risdate>2011</risdate><volume>11</volume><issue>2</issue><spage>100</spage><epage>107</epage><pages>100-107</pages><issn>1470-269X</issn><eissn>1473-1150</eissn><abstract>The role of pharmacogenomics and tamoxifen was investigated by analyzing several polymorphisms of cytochrome P450 and SULT1A1 gene in a nested case control study from the Italian Tamoxifen Prevention Trial. This study included 182 Caucasian subjects, 47 breast cancer (BC) cases and 135 matched controls. We used the AmpliChip CYP450 Test to screen 33 alleles of CYP2D6 and 3 of CYP2C19. One more variant for CYP2C19
*
17 and two single-nucleotide polymorphisms for the gene
SULT1A1
were also performed. By using the AmpliChip CYP450 Test, out of 182 subjects, we identified 8 poor metabolizer (PM), 17 intermediate metabolizer (IM), 151 extensive metabolizer (EM) and 3 ultrarapid metabolizer (UM). PM women allocated to the tamoxifen arm showed a higher risk of developing BC compared to the remaining phenotypes (
P
=0.035). In an exploratory analysis, among 58 women with a CYP2D6
*
2A allele, 9 BCs were diagnosed in the placebo arm and only 1 in the tamoxifen arm (
P
=0.0001). CYP2C19 and SULT1A1 polymorphisms did not show any correlation with tamoxifen efficacy. Tamoxifen showed reduced efficacy in CYP2D6 PMs in the chemoprevention setting. Conversely, the CYP2D6
*
2A allele may be associated with increased efficacy of tamoxifen. These findings support the relevance of pharmaco-genomics in tailoring tamoxifen treatment.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>20309015</pmid><doi>10.1038/tpj.2010.17</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | The pharmacogenomics journal, 2011-04, Vol.11 (2), p.100-107 |
| issn | 1470-269X 1473-1150 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_874180524 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | 631/92/436/108 692/699/67/1347 692/699/67/1857 692/700/565/1436/434 Alleles Antineoplastic Agents, Hormonal - therapeutic use Aryl Hydrocarbon Hydroxylases - genetics Arylsulfotransferase - genetics Biomedical and Life Sciences Biomedicine Breast cancer Breast Neoplasms - prevention & control Care and treatment Case-Control Studies Clinical Trials as Topic Complications and side effects CYP2D6 protein Cytochrome Cytochrome P-450 Cytochrome P-450 CYP2C19 Cytochrome P-450 CYP2D6 - genetics Cytochrome P450 Drug Resistance, Neoplasm - genetics Female Gene Expression Health aspects Human Genetics Humans Italy Middle Aged Oncology original-article Pharmacogenomics Pharmacotherapy Phenotypes Polymorphism, Single Nucleotide Prevention Psychopharmacology Risk factors Single nucleotide polymorphisms Single-nucleotide polymorphism Tamoxifen Tamoxifen - therapeutic use Treatment Outcome |
| title | Efficacy of tamoxifen based on cytochrome P450 2D6, CYP2C19 and SULT1A1 genotype in the Italian Tamoxifen Prevention Trial |
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