CONGENITAL-ABNORMALITIES IN CHILDREN WITH ACUTE-LEUKEMIA - A REPORT FROM THE CHILDRENS CANCER GROUP

Objective: To evaluate the risk of leukemia associated with congenital abnormalities, a series of matched case-control studies were carried out by the Children's Cancer Group. Study design: Eligible case patien ts for this analysis included individuals with a diagnosis of leukemia confirmed at a Children's Cancer Group member institution: 2117 diagn osed with acute lymphoblastic leukemia (ALL) and 605 diagnosed with ac ute myelogenous leukemia (AML). Case patients were compared with match ed regional population control subjects selected by using a modified r andom digit dialing method. Data regarding congenital abnormalities in index children and their siblings were collected by telephone intervi ew with the biologic mother. Relative risk was estimated by using the odds ratio (OR). Results: More congenital abnormalities were reported in index case patients with ALL than in control subjects, with statist ically significant increases in multiple birthmarks (OR = 1.35), Down syndrome (OR = 4.85), congenital heart defects (OR = 1.48), and pancre as-digestive tract abnormalities (OR = 2.52). Similarly, birth defects were reported more often among index case patients with AML than cont rol subjects (OR = 2.90), with significant increases in multiple birth marks (OR = 1.89), Down syndrome (OR = 76.80), mental retardation (OR = 14.47), and congenital heart defects (OR = 2.07). Exclusion of case patients with Down syndrome from the analysis did not change the stati stically significant excess of pancreas-digestive tract abnormalities in case patients with ALL or the excess of multiple birthmarks observe d in both case patients with ALL and those with AML. For both the ALL and AML analyses, no significant differences in the number of reported congenital abnormalities were seen between siblings of case patients and siblings of control subjects. Conclusion: Many of the observed ass ociations with congenital abnormalities occurred in the children with Down syndrome, who are known to have an increased risk for leukemia. T he higher reported frequency of birthmarks among case patients may sug gest a genetic component to leukemia risk.