title: In utero cytomegalovirus infection and development of childhood acute lymphoblastic leukemia.
abstract: It is widely suspected, yet controversial, that infection plays an etiologic role in the development of acute lymphoblastic leukemia (ALL), the most common childhood cancer and a disease with a confirmed prenatal origin in most cases. We investigated infections at diagnosis and then assessed the timing of infection at birth in children with ALL and age, gender, and ethnicity matched controls to identify potential causal initiating infections. Comprehensive untargeted virome and bacterial analyses of pretreatment bone marrow specimens (n = 127 ALL in comparison with 38 acute myeloid leukemia cases in a comparison group) revealed prevalent cytomegalovirus (CMV) infection at diagnosis in childhood ALL, demonstrating active viral transcription in leukemia blasts as well as intact virions in serum. Screening of newborn blood samples revealed a significantly higher prevalence of in utero CMV infection in ALL cases (n = 268) than healthy controls (n = 270) (odds ratio [OR], 3.71, confidence interval [CI], 1.56-7.92,P= .0016). Risk was more pronounced in Hispanics (OR=5.90, CI=1.89-25.96) than in non-Hispanic whites (OR=2.10 CI= 0.69-7.13). This is the first study to suggest that congenital CMV infection is a risk factor for childhood ALL and is more prominent in Hispanic children. Further investigation of CMV as an etiologic agent for ALL is warranted.
authors.affiliation: Department of Epidemiology, University of California, Berkeley, CA.|Helen Diller Family Comprehensive Cancer Center and Departments of Neurological Surgery and Epidemiology and Biostatistics and.
authors.forename: Stephen Starko
authors.initials: SS
authors.lastname: Francis
authors.affiliation: Department of Epidemiology, University of California, Berkeley, CA.
authors.forename: Amelia D
authors.initials: AD
authors.lastname: Wallace
authors.affiliation: Department of Epidemiology, University of California, Berkeley, CA.
authors.forename: George A
authors.initials: GA
authors.lastname: Wendt
authors.affiliation: Blood Systems Research Institute, Department of Laboratory Medicine, University of California, San Francisco, CA.
authors.forename: Linlin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Vaccinology and Infectious Diseases, University of California, Berkeley, CA.
authors.forename: Fenyong
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Epidemiology, University of California, Berkeley, CA.|Blood Systems Research Institute, Department of Laboratory Medicine, University of California, San Francisco, CA.
authors.forename: Lee W
authors.initials: LW
authors.lastname: Riley
authors.affiliation: Helen Diller Family Comprehensive Cancer Center and Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA.
authors.forename: Scott
authors.initials: S
authors.lastname: Kogan
authors.affiliation: Helen Diller Family Comprehensive Cancer Center and Departments of Neurological Surgery and Epidemiology and Biostatistics and.
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Walsh
authors.affiliation: Helen Diller Family Comprehensive Cancer Center and Departments of Neurological Surgery and Epidemiology and Biostatistics and.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: de Smith
authors.affiliation: Pediatric Hematology/Oncology, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA.
authors.forename: Gary V
authors.initials: GV
authors.lastname: Dahl
authors.affiliation: Department of Chronic Disease Epidemiology, School of Public Health, Yale University, New Haven, CT.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Ma
authors.affiliation: Blood Systems Research Institute, Department of Laboratory Medicine, University of California, San Francisco, CA.
authors.forename: Eric
authors.initials: E
authors.lastname: Delwart
authors.affiliation: Department of Epidemiology, University of California, Berkeley, CA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Metayer
authors.affiliation: Helen Diller Family Comprehensive Cancer Center and Departments of Neurological Surgery and Epidemiology and Biostatistics and.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Wiemels
mesh_terms: D001856:Bone Marrow Examination; D016022:Case-Control Studies; D003586:Cytomegalovirus Infections / Q000150:complications* / Q000151:congenital / Q000208:ethnology; D006630:Hispanic or Latino; D006801:Humans; D007231:Infant, Newborn; D015997:Neonatal Screening / Q000379:methods*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000209:etiology / Q000821:virology*; D015995:Prevalence; D044465:White People