The occurrence of cancer and neurological disorders in first- and second-degree relatives of children in the United States and Canada diagnosed with brain tumor before age six was investigated. A pair-matched casecontrol study with 155 astrocytoma and 166 primitive neuroectodermal tumor (PNET) cases was performed. Cases were identified through the Childrens Cancer Group. Controls were selected by random-digit dialing and matched to cases on age, race, and telephone area code and exchange. Childhood cancers were more common in PNET relatives compared with the general population (standardized incidence ratio [SIR]=2.5, 95 percent confidence interval [CI] 1.1–4.8,
P=0.02) and with control relatives (odds ratio [OR]=3.0, CI=0.5–30,
P=0.29). For astrocytoma, nonsignificant excesses of brain tumor, leukemia/lymphoma, and childhood cancer occurred among case relatives compared with control relatives, but not compared with the general population. Astrocytoma cases were significantly more likely than controls to have a relative with seizures (OR=2.5, CI=1.2–4.9,
P=0.009), especially childhood seizures (OR=3.4, CI=1.2–12,
P=0.02), epilepsy (OR=3.0, CI=0.9–13,
P=0.08), and febrile convulsions (OR=4.5, CI=0.9–43,
P=0.07). A family history of stroke was not a risk factor for either type of brain tumor. These results suggest that some childhood brain tumors may result from a genetic susceptibility and that some risk factors may affect childhood astrocytoma and PNET differently.
Key words Astrocytoma - case-control study - childhood brain tumors - family history - North America - primitive neuroectodermal tumor
Drs Rorke, Meadows, and Bunin are with the Children's Hospital of Philadelphia, University of Pennsylvania, School of Medicine, Philadelphia, PA, USA. Dr Kuijten was at the Children's Hospital of Philadelphia but is now at McKinsey and Company, Amsterdam, The Netherlands. Dr Strom is with The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. Dr Boesel is with Columbus Children's Hospital, Columbus, OH, USA. Dr Buckley is with the School of Medicine, University of Southern California, Los Angeles, CA, USA. Address correspondence to The Childrens Cancer Group, P.O. Box 60012, Arcadia, CA 91066-6012. Work was performed at the Children's Hospital of Philadelphia, Division of Oncology, Department of Pediatrics, University of Pennsylvania, School of Medicine, Philadelphia, PA 19104, USA. This research (Childrens Cancer Group protocol No. E12) was supported in part by US National Institutes of Health grant CA 29275. Contributing Childrens Cancer Group Investigators, Institutions, and Grant Numbers are given in the Appendix. Grant support from the Division of Cancer Treatment, National Cancer Institutes of Health, Department of Health and Human Services. The work reported in this paper was undertaken during the tenure of a Research Training Fellowship awarded to Dr Kuijten by the International Agency for Research on Cancer, World Health Organization, Lyon, France.