HISTORY OF MATERNAL-FETAL LOSS AND INCREASED RISK OF CHILDHOOD ACUTE-LEUKEMIA AT AN EARLY AGE - A REPORT FROM THE CHILDRENS CANCER GROUP

Background. Maternal reproductive history of fetal loss previously has been reported to be associated with an increased risk of leukemia in subsequent offspring. Data from a Childrens Cancer Group (CCG) case-co ntrol study were analyzed to test the hypothesis that this association was dependent on the number of previous fetal losses and age at leuke mia diagnosis. Methods. A case-control study using a large Childrens C ancer Group database examined maternal history of fetal loss as a risk factor for childhood leukemia in subsequent offspring. One thousand s even hundred fifty-three patients with childhood acute leukemia were c ompared with 839 community control subjects s and 2081 nonleukemia can cer control subjects. Results. A modest increase in risk was found to be associated with a history of fetal loss. Stratification by age at d iagnosis of leukemia showed that this association was significant only for those patients diagnosed before 4 years of age and most significa nt in those patients diagnosed before 2 years of age. When comparing c ommunity controls with patients acute lymphocytic leukemia diagnosed b efore 2 years of age, one previous fetal loss was associated with a fi ve-fold increased risk (P < 0.001) whereas two or more fetal losses we re associated with a relative risk of 24.8 (P < 0.001). Similarly, pat ients with acute myelocytic leukemia diagnosed before 2 years of age d emonstrated 5-fold and 12-fold increased risks associated with the pre vious fetal loss and 2 or more previous fetal losses, respectively. Co nclusions. Childhood acute leukemia occurring at younger ages may be a ssociated with an underlying genetic abnormality or chronic environmen tal exposure, which can be either lethal to the developing fetus or mu tagenic and result in the development of acute leukemia.