Activation of maternal Epstein-Barr virus infection and risk of acute leukemia in the offspring

Rosamaria Tedeschi, Aini Bloigu, Helga M. Ögmundsdottir, Alessia Marus, Joakim Dillner, Paolo DePaoli, Margret Gudnadottir, Pentti Koskela, Eero Pukkala, Tuula Lehtinen, Matti Lehtinen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)134-137
Number of pages4
JournalAmerican Journal of Epidemiology
Volume165
Issue number2
DOIs
Publication statusPublished - Jan 2007

Bibliographical note

Funding Information:
This study was supported by the European Union (grant LSHC-CT-2004-503465). This paper is work number 40 of the Nordic Biological Specimen Banks on Cancer Causes and Control. Marjo Kaasila and Ettore Bidoli are gratefully acknowledged for their assistance with the statistical analysis. Conflict of interest: none declared.

Other keywords

  • Antibodies
  • Case-control studies
  • Child
  • Epstein-Barr virus infections
  • Finland
  • Iceland
  • Leukemia
  • Leukemia, lymphocytic, acute

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