title: Single nucleotide polymorphism in IL1B is associated with infection risk in paediatric acute myeloid leukaemia.
abstract: We evaluated single nucleotide polymorphisms (SNPs) associated with infection risk in children with newly diagnosed acute myeloid leukaemia (AML). We conducted a multicentre, prospective cohort study that included children aged ≤18 years with de novo AML. DNA was isolated from blood lymphocytes or buccal swabs, and candidate gene SNP analysis was conducted. Primary outcome was the occurrence of microbiologically documented sterile site infection during chemotherapy. Secondary outcomes were Gram-positive and -negative infections, viridans group streptococcal infection and proven/probable invasive fungal infection. Interpretation was guided by consistency in risk alleles and microbiologic agent with previous literature. Over the study period 254 children and adolescents with AML were enrolled. Overall, 190 (74.8%) had at least one sterile site microbiologically documented infection. Among the 172 with inferred European ancestry and DNA available, nine significant associations were observed; two were consistent with previous literature. Allele A at IL1B (rs16944) was associated with decreased microbiologically documented infection, and allele G at IL10 (rs1800896) was associated with increased risk of Gram-positive infection. We identified SNPs associated with infection risk in paediatric AML. Genotype may provide insight into mechanisms of infection risk that could be used for supportive-care novel treatments.
authors.affiliation: Division of Haematology/Oncology, Ontario, Canada; Child Health Evaluative Sciences, Ontario, Canada. Electronic address: lillian.sung@sickkids.ca.
authors.forename: L
authors.initials: L
authors.lastname: Sung
authors.affiliation: Pediatric Hematology/Oncology, British Columbia Children's Hospital, Vancouver, British Columbia, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Dix
authors.affiliation: Hematology/Oncology, Hopital Sainte-Justine, Montreal, Quebec, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Cellot
authors.affiliation: Child Health Evaluative Sciences, Ontario, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Gillmeister
authors.affiliation: Child Health Evaluative Sciences, Ontario, Canada.
authors.forename: M C
authors.initials: MC
authors.lastname: Ethier
authors.affiliation: Program in Genetics and Genome Biology, Ontario, Canada.
authors.forename: N M
authors.initials: NM
authors.lastname: Roslin
authors.affiliation: Hematology Oncology, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
authors.forename: D L
authors.initials: DL
authors.lastname: Johnston
authors.affiliation: Department of Hematology/Oncology, Children's Hospital and Research Center, Oakland, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Feusner
authors.affiliation: Hematology/Oncology, Montreal Children's Hospital, Montreal, Quebec, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Mitchell
authors.affiliation: Hematology/Oncology/Transplant Program, Alberta Children's Hospital, Calgary, Alberta, Canada.
authors.forename: V
authors.initials: V
authors.lastname: Lewis
authors.affiliation: Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Aplenc
authors.affiliation: Hematology/Oncology, CancerCare Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Yanofsky
authors.affiliation: Hematology/Oncology, Chedoke-McMaster Hospitals, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Portwine
authors.affiliation: Pediatrics, IWK Health Centre, Halifax, Nova Scotia, Canada.
authors.forename: V
authors.initials: V
authors.lastname: Price
authors.affiliation: Hematology/Oncology, London Health Sciences, Victoria Hospital, London, Ontario, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Zelcer
authors.affiliation: Hematology/Oncology, Cancer Centre of Southeastern Ontario, Kingston, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Silva
authors.affiliation: Hematology/Oncology, Janeway Child Health Centre, St. John's, Newfoundland, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Bowes
authors.affiliation: Pediatric Hematology/OncologyCentre, Hospitalier Universitaire de Quebec, Quebec, Quebec, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Michon
authors.affiliation: Stollery Children's Hospital, University of Alberta Hospital, Edmonton, Alberta, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Stobart
authors.affiliation: Department of Diagnostic Imaging, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Traubici
authors.affiliation: Division of Infectious Diseases, Ontario, Canada.
authors.forename: U
authors.initials: U
authors.lastname: Allen
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Beyene
authors.affiliation: Histocompatibility Laboratory, University Health Network, Ontario, Canada.
authors.forename: N
authors.initials: N
authors.lastname: den Hollander
authors.affiliation: Program in Genetics and Genome Biology, The Hospital for Sick Children, Ontario, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
authors.forename: A D
authors.initials: AD
authors.lastname: Paterson
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003141:Communicable Diseases / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000150:complications*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D018570:Risk Assessment
chemical_list: C508585:IL1B protein, human; D053583:Interleukin-1beta
keywords: Acute myeloid leukaemia; infection; paediatrics; prediction; single nucleotide polymorphisms