Paternal military service and risk of leukemia among children with Down syndrome: A children’s oncology group (COG) study

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1068 Active military service may be a surrogate measure for hazardous exposures, such as defoliant agents (e.g., Agent Orange) used widely in the Vietnam War. Such exposures are cause for ongoing health concern among current and former military employees and their families. A prior COG epidemiologic study reported that paternal military service in Vietnam or Cambodia was associated with a modestly increased risk of acute myeloid leukemia (AML) in children; however, the Institute of Medicine concluded in 2004 that there is inadequate information to determine whether or not an association exists between parental military service and cancer in offspring. Children with Down syndrome (DS) have a 10-to-20-fold increased risk of developing acute leukemia compared to children without DS and are therefore a valuable population for the study of leukemia etiology. The purpose of this case-control study analysis was to examine the possible association between paternal military service and acute leukemia in children with DS. Children with DS (controls) were frequency matched by age to children with DS and leukemia (cases) diagnosed in 1997-2002 at ages 0-19 years at participating COG institutions in North America. Fathers (n=275), and mothers serving as surrogates (n=40), of 152 cases (n=93 acute lymphoblastic leukemia (ALL) and n=59 AML) and 163 controls were asked to complete a one-hour telephone interview, including items regarding paternal military service. Unconditional logistic regression was employed to evaluate the association, resulting in odds ratios (ORs) and 95% confidence intervals (CIs). Reference age, paternal age at the time of the index child’s birth, paternal race, and paternal alcohol use were included in the final multivariate models. There was little evidence to support an association between any paternal military service (OR=1.12, 95% CI: 0.95-1.31), service in Vietnam or Cambodia (OR= 2.26, 95% CI: 0.41-12.49), or service in other countries (OR=0.91, 95% CI: 0.40-2.11) and leukemia in the offspring. Similar results were observed among ALL and AML cases analyzed separately. These null results are generally consistent with those from the previous COG study, which found that paternal military service was not associated with leukemia in offspring (not restricted to children with DS); however, our results failed to replicate the former finding that service in Vietnam or Cambodia was modestly associated with AML. Service in Vietnam or Cambodia is a poor surrogate for Agent Orange exposure and is a limitation of the current study; future research should utilize more sophisticated exposure assessment methods. Overall, we found little evidence in support of a causal association between paternal military service and leukemia in children with DS.
 Research supported by NIH Grants R01 CA75169 and T32 CA099936 and the Children’s Cancer Research Fund, Minneapolis, MN.

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