Chong Wang, Mary Hwang, Brandon Paulson, Doreen Mhandire, Sadat Ozair, Tracey L O'Connor, Shipra Gandhi, Kristopher M Attwood, Daniel L Hertz, Andrew Kl Goey
{"title":"SULT2A1和ABCG2变异等位基因与帕博西尼毒性风险增加的潜在关联。","authors":"Chong Wang, Mary Hwang, Brandon Paulson, Doreen Mhandire, Sadat Ozair, Tracey L O'Connor, Shipra Gandhi, Kristopher M Attwood, Daniel L Hertz, Andrew Kl Goey","doi":"10.1080/14622416.2024.2380240","DOIUrl":null,"url":null,"abstract":"<p><p><b>Aim:</b> This study evaluated associations between <i>CYP3A4*22</i> and variants in other pharmacogenes (<i>CYP3A5</i>, <i>SULT2A1</i>, <i>ABCB1</i>, <i>ABCG2</i>, <i>ERCC1</i>) and the risk for palbociclib-associated toxicities.<b>Materials & methods:</b> Two hundred cancer patients who received standard-of-care palbociclib were genotyped and associations with toxicity were evaluated retrospectively.<b>Results:</b> No significant associations were found for <i>CYP3A4*22</i>, <i>CYP3A5*3</i>, <i>ABCB1</i>_rs1045642, <i>ABCG2</i>_rs2231142, <i>ERCC1</i>_rs3212986 and <i>ERCC1</i>_rs11615. Homozygous variant carriers of <i>SULT2A1</i>_rs182420 had higher incidence of dose modifications due to palbociclib toxicity (odds ratio [OR]: 4.334, 95% CI: 1.057-17.767, <i>p</i> = 0.042). <i>ABCG2_rs2231137</i> variant carriers had borderline higher incidence of grade 3-4 neutropenia (OR: 4.14, 95% CI: 0.99-17.37, <i>p</i> = 0.052).<b>Conclusion:</b> Once validated, <i>SULT2A1</i> and <i>ABCG2</i> variants may be useful to individualize palbociclib dosing to minimize toxicities and improve treatment outcomes.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Potential association of <i>SULT2A1</i> and <i>ABCG2</i> variant alleles with increased risk for palbociclib toxicity.\",\"authors\":\"Chong Wang, Mary Hwang, Brandon Paulson, Doreen Mhandire, Sadat Ozair, Tracey L O'Connor, Shipra Gandhi, Kristopher M Attwood, Daniel L Hertz, Andrew Kl Goey\",\"doi\":\"10.1080/14622416.2024.2380240\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b>Aim:</b> This study evaluated associations between <i>CYP3A4*22</i> and variants in other pharmacogenes (<i>CYP3A5</i>, <i>SULT2A1</i>, <i>ABCB1</i>, <i>ABCG2</i>, <i>ERCC1</i>) and the risk for palbociclib-associated toxicities.<b>Materials & methods:</b> Two hundred cancer patients who received standard-of-care palbociclib were genotyped and associations with toxicity were evaluated retrospectively.<b>Results:</b> No significant associations were found for <i>CYP3A4*22</i>, <i>CYP3A5*3</i>, <i>ABCB1</i>_rs1045642, <i>ABCG2</i>_rs2231142, <i>ERCC1</i>_rs3212986 and <i>ERCC1</i>_rs11615. Homozygous variant carriers of <i>SULT2A1</i>_rs182420 had higher incidence of dose modifications due to palbociclib toxicity (odds ratio [OR]: 4.334, 95% CI: 1.057-17.767, <i>p</i> = 0.042). <i>ABCG2_rs2231137</i> variant carriers had borderline higher incidence of grade 3-4 neutropenia (OR: 4.14, 95% CI: 0.99-17.37, <i>p</i> = 0.052).<b>Conclusion:</b> Once validated, <i>SULT2A1</i> and <i>ABCG2</i> variants may be useful to individualize palbociclib dosing to minimize toxicities and improve treatment outcomes.</p>\",\"PeriodicalId\":20018,\"journal\":{\"name\":\"Pharmacogenomics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmacogenomics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/14622416.2024.2380240\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/8/2 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacogenomics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/14622416.2024.2380240","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/2 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Potential association of SULT2A1 and ABCG2 variant alleles with increased risk for palbociclib toxicity.
Aim: This study evaluated associations between CYP3A4*22 and variants in other pharmacogenes (CYP3A5, SULT2A1, ABCB1, ABCG2, ERCC1) and the risk for palbociclib-associated toxicities.Materials & methods: Two hundred cancer patients who received standard-of-care palbociclib were genotyped and associations with toxicity were evaluated retrospectively.Results: No significant associations were found for CYP3A4*22, CYP3A5*3, ABCB1_rs1045642, ABCG2_rs2231142, ERCC1_rs3212986 and ERCC1_rs11615. Homozygous variant carriers of SULT2A1_rs182420 had higher incidence of dose modifications due to palbociclib toxicity (odds ratio [OR]: 4.334, 95% CI: 1.057-17.767, p = 0.042). ABCG2_rs2231137 variant carriers had borderline higher incidence of grade 3-4 neutropenia (OR: 4.14, 95% CI: 0.99-17.37, p = 0.052).Conclusion: Once validated, SULT2A1 and ABCG2 variants may be useful to individualize palbociclib dosing to minimize toxicities and improve treatment outcomes.
期刊介绍：
Pharmacogenomics (ISSN 1462-2416) is a peer-reviewed journal presenting reviews and reports by the researchers and decision-makers closely involved in this rapidly developing area. Key objectives are to provide the community with an essential resource for keeping abreast of the latest developments in all areas of this exciting field.
Pharmacogenomics is the leading source of commentary and analysis, bringing you the highest quality expert analyses from corporate and academic opinion leaders in the field.
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