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American Journal of Epidemiology Advance Access published online on September 27, 2006
American Journal of Epidemiology, doi:10.1093/aje/kwj332
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American Journal of Epidemiology Copyright © 2006 by the Johns Hopkins Bloomberg School of Public Health All rights reserved; printed in U.S.A.
Received March 11, 2006
Accepted June 2, 2006

ORIGINAL CONTRIBUTIONS

Activation of Maternal Epstein-Barr Virus Infection and Risk of Acute Leukemia in the Offspring

Rosamaria Tedeschi 1, Aini Bloigu 2, Helga M. Ögmundsdottir 3, Alessia Marus 1, Joakim Dillner 4, Paolo dePaoli 1, Margret Gudnadottir 5, Pentti Koskela 2, Eero Pukkala 6, Tuula Lehtinen 7, and Matti Lehtinen 8 *

1 Department of Microbiology, Oncological Center, Aviano, Italy
2 National Public Health Institute, Oulu, Finland
3 Icelandic Cancer Society, Reykjavik, Iceland; Molecular and Cell Biology Research Laboratory, University of Iceland, Reykjavik, Iceland
4 Department of Medical Microbiology, University of Lund, Malmö, Sweden
5 Molecular and Cell Biology Research Laboratory, University of Iceland, Reykjavik, Iceland
6 Institute for Statistical and Epidemiological Cancer Research, Finnish Cancer Registry, Helsinki, Finland
7 Medical Faculty, University of Tampere, Tampere, Finland
8 National Public Health Institute, Oulu, Finland; Medical Faculty, University of Tampere, Tampere, Finland

* To whom correspondence should be addressed.
Matti Lehtinen, E-mail: llmale{at}uta.fi


  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.

Keywords: antibodies; case-control studies; child; Epstein-Barr virus infections; Finland; Iceland; leukemia; leukemia, lymphocytic, acute.
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