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Am J Epidemiol 2003; 158:207-213.
Copyright © 2003 by Johns Hopkins Bloomberg School of Public Health


ORIGINAL CONTRIBUTIONS

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

Matti Lehtinen1 , Pentti Koskela2, Helga M. Ögmundsdottir3,4, Aini Bloigu2, Joakim Dillner5, Margret Gudnadottir4, Timo Hakulinen6, Anne Kjartansdottir5, Matias Kvarnung7, Eero Pukkala8, Hrafn Tulinius3,4 and Tuula Lehtinen9

1 Department of Infectious Disease Epidemiology, National Public Health Institute, Helsinki, Finland.
2 Department of Microbiology, National Public Health Institute, Oulu, Finland.
3 Icelandic Cancer Registry, Icelandic Cancer Society, Reykjavik, Iceland.
4 Medical School, University of Iceland, Reykjavik, Iceland.
5 Department of Clinical Microbiology, Malmö Central Hospital, Malmö, Sweden.
6 Department of Public Health, University of Helsinki, Helsinki, Finland.
7 Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.
8 Finnish Cancer Registry, Helsinki, Finland.
9 Medical School, University of Tampere, Tampere, Finland.

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.

antibodies; child; Epstein-Barr virus infections; herpesvirus 4, human; leukemia, lymphocytic, acute; longitudinal studies; prospective studies

Abbreviations: 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.


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