title: Constitutional sequence variation in the Fanconi anaemia group C (FANCC) gene in childhood acute myeloid leukaemia.
abstract: The extent to which genetic susceptibility contributes to the causation of childhood acute myeloid leukaemia (AML) is not known. The inherited bone marrow failure disorder Fanconi anaemia (FA) carries a substantially increased risk of AML, raising the possibility that constitutional variation in the FA (FANC) genes is involved in the aetiology of childhood AML. We have screened genomic DNA extracted from remission blood samples of 97 children with sporadic AML and 91 children with sporadic acute lymphoblastic leukaemia (ALL), together with 104 cord blood DNA samples from newborn children, for variations in the Fanconi anaemia group C (FANCC) gene. We found no evidence of known FANCC pathogenic mutations in children with AML, ALL or in the cord blood samples. However, we detected 12 different FANCC sequence variants, of which five were novel to this study. Among six FANCC variants leading to amino-acid substitutions, one (S26F) was present at a fourfold greater frequency in children with AML than in the cord blood samples (odds ratio: 4.09, P = 0.047; 95% confidence interval 1.08-15.54). Our results thus do not exclude the possibility that this polymorphic variant contributes to the risk of a small proportion of childhood AML.
authors.affiliation: Immunogenetics Laboratory, Central Manchester and Manchester Children's University Hospitals NHS Trust,University of Manchester, Hathersage Road, Manchester M13 0JH, UK. Lisa.Barber@man.ac.uk
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Barber
authors.forename: Helen E N
authors.initials: HE
authors.lastname: McGrath
authors.forename: Stefan
authors.initials: S
authors.lastname: Meyer
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Will
authors.forename: Jillian M
authors.initials: JM
authors.lastname: Birch
authors.forename: Osborn B
authors.initials: OB
authors.lastname: Eden
authors.forename: G Malcolm
authors.initials: GM
authors.lastname: Taylor
mesh_terms: D000208:Acute Disease; D016022:Case-Control Studies; D018797:Cell Cycle Proteins; D002648:Child; D016001:Confidence Intervals; D004268:DNA-Binding Proteins; D005199:Fanconi Anemia / Q000235:genetics; D052218:Fanconi Anemia Complementation Group C Protein; D051856:Fanconi Anemia Complementation Group Proteins; D005312:Fetal Blood; D020022:Genetic Predisposition to Disease; D006801:Humans; D007231:Infant, Newborn; D007951:Leukemia, Myeloid / Q000235:genetics*; D009687:Nuclear Proteins; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D012306:Risk
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C497651:FANCC protein, human; D052218:Fanconi Anemia Complementation Group C Protein; D051856:Fanconi Anemia Complementation Group Proteins; D009687:Nuclear Proteins; D011506:Proteins