{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:20:05Z","timestamp":1790878805670,"version":"4.1.0"},"reference-count":74,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T00:00:00Z","timestamp":1752624000000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873094"],"award-info":[{"award-number":["81873094"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cyclophosphamide (CTX) is one of the most widely used drugs in the clinical treatment of tumors and autoimmune diseases. The correlation between CYP, GST, and ABC gene polymorphisms and CTX activity and its induced toxicity has been extensively studied, but with inconsistent conclusions. In this study, a meta\u2010analysis protocol was employed to comprehensively evaluate the relationship between the gene polymorphisms, including CYP2C9, CYP2C19, CYP2B6, CYP3A5, GSTA1, GSTM1, GSTT1, GSTP1, ABCB1, ABCC4, and ABCG2, and the safety and efficacy of CTX. Forty\u2010five eligible literatures were retrieved from PubMed, Web of Science, Embase, and China National Knowledge Infrastructure (CNKI) databases. The results showed that CYP, GST, and ABC gene polymorphisms analyzed in the study were not associated with the efficacy but related to the safety of CTX. CYP2C19*2 polymorphism showed low risk with CTX\u2010induced gastrointestinal toxicity (RR, 3.70; 95% CI, 1.60\u20138.55;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.002). The GSTT1\u2010present genotype showed low risk with hematological (RR, 0.63; 95% CI, 0.42\u20130.96;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.03), gastrointestinal toxicity (RR, 0.62; 95% CI, 0.41\u20130.94;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.02) and other toxicities (RR, 0.60; 95% CI, 0.38\u20130.97;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.04). The GSTP1 (rs1695) wild\u2010type showed low risk with gastrointestinal toxicity (RR, 0.69; 95% CI, 0.52\u20130.92;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.01). Additionally, the ABCC4 (rs9561778) wild\u2010type also showed low risk with gastrointestinal toxicity (RR, 0.50; 95% CI, 0.28\u20130.88;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.02). Our findings confirm that the polymorphisms of CYP2C19*2, GSTT1, GSTP1 (rs1695), and ABCC4 (rs9561778) play an important role in predicting the risk of hematological, gastrointestinal, and other toxicities in patients undergoing CTX treatment.\n                  <\/jats:p>","DOI":"10.1111\/cts.70301","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T03:50:00Z","timestamp":1752724200000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Influence of Genetic Variation of\n                    <scp>GST<\/scp>\n                    ,\n                    <scp>CYP<\/scp>\n                    , and\n                    <scp>ABC<\/scp>\n                    on the Safety and Efficacy of Cyclophosphamide\u2010Based Therapy"],"prefix":"10.1111","volume":"18","author":[{"given":"Zhong\u2010Wei","family":"Yao","sequence":"first","affiliation":[{"name":"Drug Clinical Trial Center Taizhou School of Clinical Medicine, Nanjing Medical University  Taizhou China"},{"name":"The Affiliated Taizhou People's Hospital of Nanjing Medical University  Taizhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi\u2010Long","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Feng","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling\u2010Hui","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun\u2010Wen","family":"Wu","sequence":"additional","affiliation":[{"name":"The Affiliated Taizhou People's Hospital of Nanjing Medical University  Taizhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Lu","family":"Ren","sequence":"additional","affiliation":[{"name":"Drug Clinical Trial Center Taizhou School of Clinical Medicine, Nanjing Medical University  Taizhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui\u2010Tian","family":"Jia","sequence":"additional","affiliation":[{"name":"Drug Clinical Trial Center Taizhou School of Clinical Medicine, Nanjing Medical University  Taizhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan\u2010Pan","family":"Wang","sequence":"additional","affiliation":[{"name":"Drug Clinical Trial Center Taizhou School of Clinical Medicine, Nanjing Medical University  Taizhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi\u2010Ying","family":"Fu","sequence":"additional","affiliation":[{"name":"The Affiliated Taizhou People's Hospital of Nanjing Medical University  Taizhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Zhu","sequence":"additional","affiliation":[{"name":"Drug Clinical Trial Center Taizhou School of Clinical Medicine, Nanjing Medical University  Taizhou China"},{"name":"The Affiliated Taizhou People's Hospital of Nanjing Medical University  Taizhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,16]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-011-0245-0"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2014.04.009"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2009.03.034"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-9556(24)15302-0"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.tpj.6500330"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.15.176"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2007.03020.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-07-516666"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2018.04.007"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfu233"},{"key":"e_1_2_9_12_1","first-page":"6215","article-title":"Involvement of Human Glutathione S\u2010Transferase Isoenzymes in the Conjugation of Cyclophosphamide Metabolites With Glutathione","volume":"54","author":"Dirven H. 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