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Indeed, genetic variations involved in drug metabolism could, at least partially, be responsible for heterogeneous responses to standardized leukemia treatments, hence requiring more personalized therapy. The aims of this study were to (a) to determine the prevalence of seven common genetic polymorphisms including those that affect the folate and\/or thiopurine metabolic pathways, i.e. cyclinD1<\/jats:styled-content>(CCND1<\/jats:styled-content><\/jats:italic>\u2010G870A<\/jats:styled-content>), \u03b3\u2010glutamyl hydrolase (GGH<\/jats:styled-content><\/jats:italic>\u2010C452T<\/jats:styled-content>), methylenetetrahydrofolate reductase (MTHFR<\/jats:styled-content><\/jats:italic>\u2010C677T<\/jats:styled-content>andMTHFR<\/jats:styled-content><\/jats:italic>\u2010A1298C<\/jats:styled-content>), thymidylate synthase promoter (TYMS\u2010TSER<\/jats:styled-content><\/jats:italic>), thiopurine methyltransferase (TPMT<\/jats:styled-content>*3A<\/jats:styled-content><\/jats:italic>andTPMT<\/jats:styled-content>*3C<\/jats:styled-content><\/jats:italic>) and inosine triphosphate pyrophosphatase (ITPA<\/jats:styled-content>\u2010<\/jats:italic>C94A<\/jats:styled-content>), inC<\/jats:styled-content>aucasian (n<\/jats:italic>= 94, age < 20) and Vietnamese (n<\/jats:italic>= 141, age < 16 years) childhoodALL<\/jats:styled-content>and (b) to assess the impact of a multilocus genetic risk score (MGRS<\/jats:styled-content>) on relapse\u2010free survival (RFS<\/jats:styled-content>) using a Cox proportional\u2010hazards regression model.<\/jats:p><\/jats:sec>Results<\/jats:title>The prevalence ofMTHFR<\/jats:styled-content>\u2010<\/jats:italic>677TT<\/jats:styled-content>genotype was significantly higher inC<\/jats:styled-content>aucasians (P<\/jats:italic>= 0.008), in contrast to the prevalence ofTYMS\u2010TSER<\/jats:styled-content>*3R<\/jats:styled-content>\/3R<\/jats:styled-content><\/jats:italic>andITPA<\/jats:styled-content>\u2010<\/jats:italic>94AA<\/jats:styled-content>\/AC<\/jats:styled-content>genotypes which were significantly higher inV<\/jats:styled-content>ietnamese (P<\/jats:italic>< 0.001 andP<\/jats:italic>= 0.02, respectively). Compared with children with a lowMGRS<\/jats:styled-content>(\u22643), those with a highMGRS<\/jats:styled-content>(\u22654) were 2.06 (95%CI<\/jats:styled-content>= 1.01, 4.22;P<\/jats:italic>= 0.04) times more likely to relapse. AddingMGRS<\/jats:styled-content>into a multivariate Cox regression model with race\/ethnicity and four clinical variables improved the predictive accuracy of the model (AUC<\/jats:styled-content>from 0.682 to 0.709 at 24 months).<\/jats:p><\/jats:sec>Conclusion<\/jats:title>IncludingMGRS<\/jats:styled-content>into a clinical model improved the predictive accuracy of short and medium term prognosis, hence confirming the association between well determined pharmacogenotypes and outcome of paediatricALL<\/jats:styled-content>. Whether variants on other genes associated with folate metabolism can substantially improve the predictive value of currentMGRS<\/jats:styled-content>is not known but deserves further evaluation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.12481","type":"journal-article","created":{"date-parts":[[2014,8,7]],"date-time":"2014-08-07T10:37:48Z","timestamp":1407407868000},"page":"429-440","source":"Crossref","is-referenced-by-count":7,"title":["Comparative pharmacogenetic analysis of risk polymorphisms inC<\/scp>aucasian andV<\/scp>ietnamese children with acute lymphoblastic leukemia: prediction of therapeutic outcome?"],"prefix":"10.1111","volume":"79","author":[{"given":"Phuong Thu","family":"Vu Hoang","sequence":"first","affiliation":[{"name":"Centre de Technologies Mol\u00e9culaires Appliqu\u00e9es (CTMA) Institut de Recherche Exp\u00e9rimentale et Clinique (IREC) Universit\u00e9 catholique de Louvain (UCL) Brussels Belgium"},{"name":"Service d'h\u00e9matologie et oncologie 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