{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:09:41Z","timestamp":1790719781871,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2004,4,1]],"date-time":"2004-04-01T00:00:00Z","timestamp":1080777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2004,5]]},"abstract":"<jats:title>Abstract:<\/jats:title><jats:p>The significance of genetic background in childhood acute lymphoblastic leukemia (ALL) is not well understood. Polymorphisms of genes encoding for xenobiotics and drug transporters are potential factors, which can influence the risk of developing ALL and its clinical outcome. P\u2010glycoprotein (P\u2010gp) is an adenosine triphosphate\u2010binding cassette (ABC)\u2010family transporter involved in protection against xenobiotics and multi\u2010drug resistance. Recently, the single\u2010nucleotide polymorphism C3435T of <jats:italic>MDR1<\/jats:italic> gene has been found to be associated with altered tissue expression and function of P\u2010gp. To evaluate whether C3435T <jats:italic>MDR1<\/jats:italic> polymorphism is associated with the occurrence and outcome of ALL, 113 children with ALL (median age 5.1\u2003yr) and 175 healthy individuals of Polish Caucasian origin were studied by polymerase chain reaction\u2010restriction fragment\u2010length polymorhism (PCR\u2010RFLP) assay. The mutant homozygous TT genotype was found to be associated with occurrence of ALL (OR, 95% CI; 1.8, 1.1\u20133.1; <jats:italic>P<\/jats:italic>\u2003=\u20030.037). Besides, the analysis of factors influencing clinical outcome of our ALL patient cohort showed that CC genotype carriers had significantly lower event\u2010free survival probability (pEFS) (0.62 vs. 0.87; <jats:italic>P<\/jats:italic>\u2003=\u20030.007) and overall survival probability (pOS) (0.72 vs. 0.91; <jats:italic>P<\/jats:italic>\u2003=\u20030.006). The Cox proportional hazards model\u2010based analysis revealed that the hazard ratios for lower pEFS and lower pOS among CC homozygous subjects were 3.9 (<jats:italic>P<\/jats:italic>\u2003=\u20030.008) and 3.3 (<jats:italic>P<\/jats:italic>\u2003=\u20030.02), respectively. In conclusion, the results of the present study provide evidence that C3435T <jats:italic>MDR1<\/jats:italic> polymorphism may involve both the susceptibility to and the clinical outcome of childhood ALL. Carriers of the TT genotype are more at risk of developing ALL than other individuals, whereas CC genotype carriers are supposed to have worse prognosis.<\/jats:p>","DOI":"10.1111\/j.1600-0609.2004.00228.x","type":"journal-article","created":{"date-parts":[[2004,4,1]],"date-time":"2004-04-01T15:43:58Z","timestamp":1080834238000},"page":"314-321","source":"Crossref","is-referenced-by-count":146,"title":["Functional C3435T polymorphism of <i>MDR1<\/i> gene: an impact on genetic susceptibility and clinical outcome of childhood acute lymphoblastic 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