{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T09:55:14Z","timestamp":1791194114264,"version":"4.1.0"},"reference-count":79,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2001,10,8]],"date-time":"2001-10-08T00:00:00Z","timestamp":1002499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2002,1,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. The genetic factors underlying the susceptibility to this disease remain elusive. The enzymes CYP2E1, MPO and NQO1 are involved in the biotransformation of a variety of xenobiotics present in organic solvents, tobacco smoke, drugs, plastic derivatives and pesticides. They also control the level of the oxidative stress by catalyzing the formation of free radicals or by protecting cells from their deleterious effect. DNA variants in the corresponding genes have been associated with an increased susceptibility to different adult cancers, including hematologic malignancies. To investigate whether they represent risk\u2010modifying factors in childhood ALL, we conducted a case\u2010control study involving 174 patients and 337 controls, both of French\u2010Canadian origin. We found that carriers of the <jats:italic>CYP2E1*5<\/jats:italic> variant were at 2.8\u2010fold higher risk of ALL (95%CI, 1.2\u20136.4) and that <jats:italic>NQO1<\/jats:italic> alleles <jats:italic>*2<\/jats:italic> and <jats:italic>*3<\/jats:italic> contributed to the risk of ALL as well (OR = 1.7, 95%CI, 1.2\u20132.4). No such association was found with <jats:italic>MPO<\/jats:italic> alone. However, when the wild\u2010type <jats:italic>MPO<\/jats:italic> allele was considered together with the <jats:italic>CYP2E1<\/jats:italic> and <jats:italic>NQO1<\/jats:italic> risk\u2010elevating genotypes, the risk of ALL was increased further (OR = 5.4, 95%CI, 1.2\u201323.4) suggesting a combined effect. We also found a gene\u2010gene interaction between the <jats:italic>GSTM1<\/jats:italic> null genotype and <jats:italic>NQO1<\/jats:italic> mutant alleles. It is therefore plausible that exposure to xenobiotics metabolized by these enzymes play a role in the etiology of childhood ALL. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.1589","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T22:13:08Z","timestamp":1030313588000},"page":"230-236","source":"Crossref","is-referenced-by-count":113,"title":["Role of <i>NQO1<\/i>, <i>MPO<\/i> and <i>CYP2E1<\/i> genetic polymorphisms in the susceptibility to childhood acute lymphoblastic leukemia"],"prefix":"10.1002","volume":"97","author":[{"given":"Maja","family":"Krajinovic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugues","family":"Sinnett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Richer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damian","family":"Labuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Sinnett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2001,12,13]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/88.8.496"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5340.1068"},{"key":"e_1_2_6_4_2","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1182\/blood.V93.5.1496","article-title":"Susceptibility to childhood acute lymphoblastic leukemia: influence of CYP1A1, CYP2D6, GSTM1, and GSTT1 genetic polymorphisms","volume":"93","author":"Krajinovic M","year":"1999","journal-title":"Blood"},{"key":"e_1_2_6_5_2","first-page":"557","article-title":"Genetic polymorphisms of N\u2010acetyltransferase 1 (NAT1) and 2 (NAT2) and gene\u2010gene interaction in the susceptibility to childhood acute lymphoblastic leukemia","volume":"9","author":"Krajinovic M","year":"2000","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1021\/tx00022a001"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.6.2.1537462"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4274(98)00299-9"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-199812000-00011"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/18.23.7194"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a124526"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a123619"},{"key":"e_1_2_6_13_2","first-page":"29","article-title":"Hepatic messenger RNA contents of cytochrome P4502E1 in patients with different P4502E1 genotypes","volume":"29","author":"Tsutsumi M","year":"1994","journal-title":"Alcohol Alcohol"},{"key":"e_1_2_6_14_2","first-page":"4858","article-title":"Associations of CYP1A1, GSTM1, and CYP2E1 polymorphisms with lung cancer suggest cell type specificities to tobacco carcinogens","volume":"58","author":"Le Marchand L","year":"1998","journal-title":"Cancer Res"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2744(199611)17:3<144::AID-MC6>3.0.CO;2-F"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0940-2993(98)80029-8"},{"key":"e_1_2_6_17_2","first-page":"901","article-title":"et al. 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