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

Abstract

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 followup 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.

No Risk of Maternal EBV Infection for Childhood Leukemia

“…The study base comprised the prospectively followed Finnish Maternity Cohort (FCR) and Icelandic Maternity Cohort (ICR) that contain serum samples collected during the first trimester of pregnancy for screening of congenital infections, as described (6).…”

Congenital Acute Lymphoblastic Leukemia with Placental Involvement: Case Report x

“…Some authors have suggested a link between prenatal viral exposure and leukaemia risk but the only link found was the association between the Epstein-Barr virus (EBV) and ALL [7,8] and it was excluded in our case.…”

Infection as a cause of childhood leukemia: virus detection employing whole genome sequencing

“…Infection can take place in utero and reactivation of maternal EBV infection has been associated with an increased risk of childhood ALL. 22 Fetal progenitor and pre-B cells are susceptible to EBV transfection, 23 although the EBV receptor CD21 (complement receptor 2) is more commonly known as a marker for mature B cells which can be aberrantly expressed on blast cells. 24 Furthermore, early transplantation studies suggested that EBV is present in the bone marrow where quiescent pre-leukemic cells are thought to reside.…”