title: Maternal herpesvirus infections and risk of acute lymphoblastic leukemia in the offspring.
abstract: A critical role for infection in the etiology of childhood leukemia has repeatedly been suggested. The authors undertook a case-control study nested within national maternity cohorts with altogether 7 million years of follow-up to assess the relative role of three maternal herpesvirus infections in childhood acute lymphoblastic leukemia (ALL). Offspring of 550,000 mothers in Finland and Iceland formed the joint study cohort that was followed up for cancer in the offspring before age 15 years during 1975-1997 through national cancer registries. For each index mother-case pair, three or four matched control mother-control pairs were identified from national population registers. First-trimester sera were retrieved from mothers of 342 ALL and 61 other leukemia cases and from 1,216 control mothers and were tested for antibodies to cytomegalovirus, Epstein-Barr virus (EBV), and human herpesvirus 6. Serum EBV DNA was also analyzed. Conditional logistic regression-based estimates of relative risk (odds ratio) adjusted for birth order and sibship size, and population attributable fractions, were calculated. Only EBV immunoglobulin M positivity in EBV-immunoglobulin-G-positive mothers was associated with a highly significant increased risk of ALL in the offspring (adjusted odds ratio = 2.9, 95% confidence interval: 1.5, 5.8). Results indicate that reactivation of maternal EBV infection is probably associated with childhood ALL.
authors.affiliation: Department of Infectious Disease Epidemiology, National Public Health Institute, Helsinki, Finland. llmale@uta.fi
authors.forename: Matti
authors.initials: M
authors.lastname: Lehtinen
authors.forename: Pentti
authors.initials: P
authors.lastname: Koskela
authors.forename: Helga M
authors.initials: HM
authors.lastname: Ogmundsdottir
authors.forename: Aini
authors.initials: A
authors.lastname: Bloigu
authors.forename: Joakim
authors.initials: J
authors.lastname: Dillner
authors.forename: Margret
authors.initials: M
authors.lastname: Gudnadottir
authors.forename: Timo
authors.initials: T
authors.lastname: Hakulinen
authors.forename: Anne
authors.initials: A
authors.lastname: Kjartansdottir
authors.forename: Matias
authors.initials: M
authors.lastname: Kvarnung
authors.forename: Eero
authors.initials: E
authors.lastname: Pukkala
authors.forename: Hrafn
authors.initials: H
authors.lastname: Tulinius
authors.forename: Tuula
authors.initials: T
authors.lastname: Lehtinen
mesh_terms: D000328:Adult; D017668:Age of Onset; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D005260:Female; D005387:Finland / Q000453:epidemiology; D004854:Herpesvirus 4, Human / Q000472:pathogenicity*; D006801:Humans; D007055:Iceland / Q000453:epidemiology; D007075:Immunoglobulin M / Q000032:analysis; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D016017:Odds Ratio; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology / Q000209:etiology* / Q000821:virology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000821:virology*; D011261:Pregnancy Trimester, First; D012042:Registries / Q000706:statistics & numerical data; D012044:Regression Analysis; D012307:Risk Factors
chemical_list: D004279:DNA, Viral; D007075:Immunoglobulin M