Offspring of Childhood Cancer Survivors Face No Increased Risk of Genetic Disease

Despite theoretical concerns, children born to survivors of childhood cancer are at no greater risk of genetic disease than the general population, according to the largest study of its kind, published in the January issue of the American Journal of Human Genetics.

“This long-term study should dispel concerns that therapies used to treat children with cancer years ago would in turn affect their offspring,” said John Mulvihill, md, senior author of the paper and professor of human genetics at the University of Pittsburgh’s Graduate School of Public Health. “Our findings are especially important, given that now 72% of children affected by cancer survive after effective treatment with chemotherapy and/or radiation.”

Study Findings
The study was initiated at the National Cancer Institute in 1980 when Dr. Mulvihill was chief of clinical genetics. It included interviews with 1,062 adult survivors of cancer who were treated as children or teenagers between 1945 and 1975. The investigators assessed their 2,198 offspring. The frequency of genetic disease, at 3.4%, was not significantly different from the 3.1% rate discovered in 4,544 offspring of a control population of 2,043 adults who had not been treated for cancer as children.

The study defined genetic disease as malformations or disorders known to be associated with abnormalities in the cell’s chromosomes or genes. These disorders include Down syndrome, cleft palate, and cystic fibrosis. Adult survivors who were surveyed had been treated for various cancers, such as Hodgkin’s disease; muscle and bone cancers; thyroid cancers; and brain and other nervous system tumors.

Childhood cancer therapies that were considered potentially damaging included radiation therapy given below the waist and above the knees. Physicians were concerned that this treatment could damage the genes of a child’s sperm or eggs important for future reproduction. The researchers also considered chemotherapy with an alkylating agent potentially harmful to germ-line cells. Although all of the survivors were treated long ago, the same or related drugs are still in use today.

Further National Study Underway
The authors of the study cautioned that they cannot rule out the possibility that new therapeutic agents or combinations of existing agents (in higher doses) now being used to treat childhood cancer could cause permanent damage to germ-line cells. A further national study is underway with University of Pittsburgh participation.

Co-authors on the 1980 NCI study included Julianne Byrne, PhD, formerly of the NCI’s Clinical Epidemiology Branch and the Boyne Research Institute in Drogheda, Ireland, and now at Children’s National Medical Center in Washington, DC; Sonja A. Rasmussen, MD, division of genetics in the University of Florida’s department of pediatrics, Gainesville; Sandra C. Steinhorn, MS, Roger R. Connelly, MS, Max H. Myers, PhD, of the NCI’s Biometry Branch, Bethesda, Maryland; Charles F. Lynch, md, State Health Registry of Iowa, Iowa City; John Flannery, MS, Connecticut Tumor Registry, Department of Public Health, Hartford; Donald F. Austin, MD, California Tumor Registry, Department of Health Services, Emeryville, and department of public health and preventive medicine, Oregon Health Sciences University, Portland; Frederick F. Holmes, MD, and Grace E. Holmes, MD, department of pediatrics, internal medicine and preventive medicine, University of Kansas Medical Center, Kansas City; and Louise C. Strong, MD, department of experimental pediatrics/genetics, University of Texas M. D. Anderson Hospital, Houston.