title: Activation of maternal Epstein-Barr virus infection and risk of acute leukemia in the offspring.
abstract: After identifying an association between maternal Epstein-Barr virus (EBV) reactivation and acute lymphoblastic leukemia (ALL), the authors analyzed a nested case-control study within Finnish and Icelandic maternity cohorts with 7 million years of follow-up to confirm EBV's role in ALL. Offspring of 550,000 mothers were followed up to age 15 years during 1975-1997 by national cancer registries to identify leukemia cases. Mothers of cases and three quarters of matched mothers of controls were identified by national population registers. First-trimester sera from mothers of 304 ALL cases and 39 non-ALL cases and from 943 mothers of controls were analyzed for antibodies to viral capsid antigen, early antigen, and EBV transactivator protein ZEBRA. Relative risk, estimated as odds ratio (95% confidence interval), was adjusted for birth order and sibship size. Combining early antigen and/or ZEBRA immunoglobulin G antibodies with the presence of viral capsid antigen immunoglobulin M antibodies did not increase the estimate for ALL risk for viral capsid antigen immunoglobulin M alone (odds ratio = 1.9, 95% confidence interval: 1.2, 3.0). Both ZEBRA immunoglobulin G antibodies and viral capsid antigen immunoglobulin M antibodies were associated with an increased risk of non-ALL in the offspring (odds ratio = 4.5, 95% confidence interval: 1.3, 16; odds ratio = 5.6, 95% confidence interval: 1.1, 29, respectively), suggesting EBV reactivation in the mothers of non-ALL cases. EBV reactivation may be associated with a proportion of childhood leukemia.
authors.affiliation: Department of Microbiology, Oncological Center, Aviano, Italy.
authors.forename: Rosamaria
authors.initials: R
authors.lastname: Tedeschi
authors.forename: Aini
authors.initials: A
authors.lastname: Bloigu
authors.forename: Helga M
authors.initials: HM
authors.lastname: Ogmundsdottir
authors.forename: Alessia
authors.initials: A
authors.lastname: Marus
authors.forename: Joakim
authors.initials: J
authors.lastname: Dillner
authors.forename: Paolo
authors.initials: P
authors.lastname: dePaoli
authors.forename: Margret
authors.initials: M
authors.lastname: Gudnadottir
authors.forename: Pentti
authors.initials: P
authors.lastname: Koskela
authors.forename: Eero
authors.initials: E
authors.lastname: Pukkala
authors.forename: Tuula
authors.initials: T
authors.lastname: Lehtinen
authors.forename: Matti
authors.initials: M
authors.lastname: Lehtinen
mesh_terms: D000293:Adolescent; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D036022:Capsid Proteins / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000453:epidemiology / Q000821:virology; D005260:Female; D005387:Finland / Q000453:epidemiology; D005500:Follow-Up Studies; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007055:Iceland / Q000453:epidemiology; D007074:Immunoglobulin G / Q000276:immunology; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D018811:Maternal Exposure; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology / Q000209:etiology* / Q000821:virology; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000956:Antigens, Viral; D036022:Capsid Proteins; C041788:Epstein-Barr viral capsid antigen; D007074:Immunoglobulin G