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However, little is known on association between MRD status and germline genetic variation. We examined 159 Caucasian (Slavic) patients with pediatric ALL, treated according to ALL-IC-BFM 2002\/2009 protocols, in search for association between 23 germline polymorphisms and MRD status at day 15, day 33 and week 12, with adjustment for MRD-associated clinical covariates. Three variants were significantly associated with MRD: rs1544410 in <jats:italic>VDR<\/jats:italic> (MRD-day15); rs1051266 in <jats:italic>RFC<\/jats:italic> (MRD-day33, MRD-week12), independently and in an additive effect with rs10519613 in <jats:italic>IL15<\/jats:italic> (MRD-day33). The risk alleles for MRD-positivity were: A allele of <jats:italic>VDR<\/jats:italic> (OR\u2009=\u20092.37, 95%CI\u2009=\u20091.07\u20135.21, <jats:italic>P<\/jats:italic>\u2009=\u20090.03, MRD-day15); A of <jats:italic>RFC<\/jats:italic> (OR\u2009=\u20091.93, 95%CI\u2009=\u20091.05\u20133.52, <jats:italic>P<\/jats:italic>\u2009=\u20090.03, MRD-day33 and MRD-week12, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01); A of <jats:italic>IL15<\/jats:italic> (OR\u2009=\u20092.30, 95%CI\u2009=\u20091.02\u20135.18, <jats:italic>P<\/jats:italic>\u2009=\u20090.04, MRD-day33). The risk for MRD-day33-positive status was higher in patients with risk alleles in both <jats:italic>RFC<\/jats:italic> and <jats:italic>IL15<\/jats:italic> loci than in patients with risk alleles in one locus or no risk alleles: 2 vs. 1 (OR\u2009=\u20093.94, 95% CI\u2009=\u20091.28\u201312.11, <jats:italic>P<\/jats:italic>\u2009=\u20090.024), 2 vs. 0 (OR\u2009=\u20096.75, 95% CI\u2009=\u20091.61\u201328.39, <jats:italic>P<\/jats:italic>\u2009=\u20090.012). Germline variation in genes related to pharmacokinetics\/pharmacodynamics of anti-leukemic drugs and to anti-tumor immunity of the host is associated with MRD status and might help improve risk assessment in ALL.<\/jats:p>","DOI":"10.1038\/srep29427","type":"journal-article","created":{"date-parts":[[2016,7,18]],"date-time":"2016-07-18T09:15:41Z","timestamp":1468833341000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Association of germline genetic variants in RFC, IL15 and VDR genes with minimal residual disease in pediatric B-cell precursor ALL"],"prefix":"10.1038","volume":"6","author":[{"given":"Ma\u0142gorzata","family":"Dawidowska","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Kosmalska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u0141ukasz","family":"S\u0119dek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandra","family":"Szczepankiewicz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magdalena","family":"Twardoch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alicja","family":"Sonsala","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bronis\u0142awa","family":"Szarzy\u0144ska-Zawadzka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarzyna","family":"Derwich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monika","family":"Lejman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarzyna","family":"Pawelec","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnieszka","family":"Obitko-P\u0142udowska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarzyna","family":"Pawi\u0144ska-W\u0105sikowska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kinga","family":"Kwieci\u0144ska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrzej","family":"Ko\u0142tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnieszka","family":"Dyla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W\u0142adys\u0142aw","family":"Grzeszczak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerzy R.","family":"Kowalczyk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomasz","family":"Szczepa\u0144ski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewa","family":"Zi\u0119tkiewicz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Micha\u0142","family":"Witt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,7,18]]},"reference":[{"key":"BFsrep29427_CR1","doi-asserted-by":"publisher","first-page":"1943","DOI":"10.1016\/s0140-6736(12)62187-4","volume":"381","author":"H Inaba","year":"2013","unstructured":"Inaba, H., Greaves, M. & Mullighan, C. 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