Journal Article

Maternal Herpesvirus Infections and Risk of Acute Lymphoblastic Leukemia in the Offspring

Matti Lehtinen, Pentti Koskela, Helga M. Ögmundsdottir, Aini Bloigu, Joakim Dillner, Margret Gudnadottir, Timo Hakulinen, Anne Kjartansdottir, Matias Kvarnung, Eero Pukkala, Hrafn Tulinius and Tuula Lehtinen

in American Journal of Epidemiology

Published on behalf of Johns Hopkins Bloomberg School of Public Health

Volume 158, issue 3, pages 207-213
Published in print August 2003 | ISSN: 0002-9262
Published online August 2003 | e-ISSN: 1476-6256 | DOI: http://dx.doi.org/10.1093/aje/kwg137
Maternal Herpesvirus Infections and Risk of Acute Lymphoblastic Leukemia in the Offspring

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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.

Keywords: antibodies; child; Epstein-Barr virus infections; herpesvirus 4, human; leukemia, lymphocytic, acute; longitudinal studies; prospective studies; Abbreviations: ALL, acute lymphoblastic leukemia; CI, confidence interval; EBV, Epstein-Barr virus; ELISA, enzyme-linked immunosorbent assay; Ig, immunoglobulin; OR, odds ratio; PCR, polymerase chain reaction.

Journal Article.  4981 words. 

Subjects: Public Health and Epidemiology

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