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Identifying genetic variants associated with the clearance of these drugs may aid in improved dosing and outcomes. We performed genetic association studies of enzalutamide and abiraterone oral clearance in the Alliance A031201 clinical trial. Genome\u2010wide genotyping was performed with the primary analysis limited to European\u2010descent participants. Pharmacogene metabolic phenotypes were estimated using PyPGx and Stargazer. Associations of metabolic activity groups for\n                    <jats:italic>CYP3A4<\/jats:italic>\n                    ,\n                    <jats:italic>CYP3A5<\/jats:italic>\n                    ,\n                    <jats:italic>CYP2C19<\/jats:italic>\n                    and\n                    <jats:italic>SLCO1B1<\/jats:italic>\n                    with enzalutamide clearance (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u2009706) and\n                    <jats:italic>CYP3A4<\/jats:italic>\n                    ,\n                    <jats:italic>SLCO2B1<\/jats:italic>\n                    and\n                    <jats:italic>UGT1A4<\/jats:italic>\n                    with abiraterone clearance (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u2009323) were tested by linear regression. Targeted SNP associations were assessed for abiraterone clearance at loci proximal to major metabolizing genes. Full genome\u2010wide association studies were performed for both sets of clearance values. No significant associations were identified between metabolic phenotypes and enzalutamide or abiraterone oral clearance SNPs in the\n                    <jats:italic>SULT2A1<\/jats:italic>\n                    5\u2032 flanking region were significantly associated with lower abiraterone clearance, (rs296373, minor allele frequency\u2009=\u20090.15,\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2009=\u2009\u22120.457,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20093.2E\u201006). Liver protein and liver and adrenal gland gene expression QTL databases indicated significantly lower\n                    <jats:italic>SULT2A1<\/jats:italic>\n                    expression patterns for individuals carrying associated alleles, likely explaining the lower abiraterone oral clearance.\n                    <jats:italic>CYP2C8*3<\/jats:italic>\n                    was associated with higher enzalutamide clearance (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.012), but this was not significant after correction for multiple testing. This study is the first to identify the genetic association of\n                    <jats:italic>SULT2A1,<\/jats:italic>\n                    known to be involved in the metabolism of steroids in the liver and adrenal glands, with abiraterone clearance. Genetic variation in\n                    <jats:italic>SULT2A1<\/jats:italic>\n                    may be useful to inform personalized dosing of abiraterone.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                    Identifier: NCT01949337\n                  <\/jats:p>","DOI":"10.1111\/cts.70425","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T08:09:22Z","timestamp":1764922162000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of\n                    <scp>\n                      <i>SULT2A1<\/i>\n                    <\/scp>\n                    Locus With Abiraterone Clearance in the Alliance\n                    <scp>A031201<\/scp>\n                    : Randomized Phase\n          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