Activation of maternal Epstein-Barr virus infection and risk of acute leukemia in the offspring.
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.
Tedeschi
Rosamaria
R
Department of Microbiology, Oncological Center, Aviano, Italy.
Bloigu
Aini
A
Ogmundsdottir
Helga M
HM
Marus
Alessia
A
Dillner
Joakim
J
dePaoli
Paolo
P
Gudnadottir
Margret
M
Koskela
Pentti
P
Pukkala
Eero
E
Lehtinen
Tuula
T
Lehtinen
Matti
M
D000293:Adolescent; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D036022:Capsid Proteins / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000453:epidemiology / Q000821:virology; D005260:Female; D005387:Finland / Q000453:epidemiology; D005500:Follow-Up Studies; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007055:Iceland / Q000453:epidemiology; D007074:Immunoglobulin G / Q000276:immunology; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D018811:Maternal Exposure; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology / Q000209:etiology* / Q000821:virology; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors
D000888:Antibodies, Anti-Idiotypic; D000956:Antigens, Viral; D036022:Capsid Proteins; C041788:Epstein-Barr viral capsid antigen; D007074:Immunoglobulin G