Potential association of SULT2A1 and ABCG2 variant alleles with increased risk for palbociclib toxicity.

IF 1.9 4区医学 Q3 PHARMACOLOGY & PHARMACY Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2024-08-02 DOI:10.1080/14622416.2024.2380240

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

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引用次数: 0

Abstract

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.

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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。

目的：本研究评估了 CYP3A4*22 和其他药物基因（CYP3A5、SULT2A1、ABCB1、ABCG2、ERCC1）变异与帕博西尼相关毒性风险之间的关联。材料与方法对接受帕博西尼标准治疗的 200 例癌症患者进行基因分型，并回顾性评估其与毒性的关系。结果CYP3A4*22、CYP3A5*3、ABCB1_rs1045642、ABCG2_rs2231142、ERCC1_rs3212986和ERCC1_rs11615与毒性无明显关联。SULT2A1_rs182420的同源变异携带者因帕博克来毒性而调整剂量的发生率较高（几率比[OR]：4.334，95% CI：1.057-17.767，p = 0.042）。ABCG2_rs2231137变异携带者的3-4级中性粒细胞减少发生率略高（OR：4.14，95% CI：0.99-17.37，p = 0.052）。结论一旦得到验证，SULT2A1和ABCG2变异可能有助于个体化palbociclib剂量，从而最大限度地减少毒性并改善治疗效果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmacogenomics 医学-药学

CiteScore

3.40

自引率

9.50%

发文量

审稿时长

4-8 weeks

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.