GRAPEVINE, TEX. — Patients with a history of neurofibromatosis type 1 do not have an increased risk of cancer after they reach adulthood, according to findings from a study conducted in Denmark.
In a long-term follow-up study of 212 individuals with neurofibromatosis type 1 (NF1) and 128 relatives, children and adolescents with neurofibromatosis had twice the expected rate of cancer—but during adulthood, their risk of cancer was no different from that of the general population, S. Asger Sorensen, M.D., reported at a meeting sponsored by the American College of Medical Genetics.
“It was thought that patients with this disorder had a higher rate of cancer not only in childhood but in the later years of life,” said Dr. Sorensen, emeritus professor of genetics at the University of Copenhagen.
Individuals with NF1 were thought to have an increased risk of developing breast cancer or other malignancies during adulthood. “But there seems to be no excess of cancer in neurofibromatosis patients at older ages,” he said.
Neurofibromatosis—an autosomal dominant disorder that results in tumor growth—affects 1 person in 4,000, with about 100,000 Americans estimated to have the condition. These figures included both forms of the disease, type 1 and type 2.
The probands in the study had been hospitalized with the disease, whereas the affected relatives had milder cases of disease and were diagnosed only after the start of the initial study, noted John Mulvihill, M.D., professor of genetics at the University of Oklahoma Health Sciences Center, Oklahoma City.
Dr. Mulvihill, a coauthor of the study, said cancer incidence was higher in the probands who had been hospitalized than in other affected family members. “Mortality was worse in children and adolescents but much worse in the hospital-based cases than other family members who were affected. Some patients never wind up in the hospital.”
The patients, some of whom were identified as early as 1924, were first described in a 1951 study and were followed up in 1983 and 2003, Dr. Sorensen said.
In 1983, the researchers evaluated the remaining 16 NF1 patients who had been hospitalized with the disease and 26 relatives diagnosed in the 1951 study as having milder forms of NF1. By the time of the March 2003 follow-up, only five relatives were still alive.
Death certificates and hospital records were obtained for the 37 individuals who died after the 1983 follow-up. Survival curves were prepared by standard life-table methods, and the causes of death were compared with those in the general population.
At the latest follow-up, the survival rate showed the same trend as that observed at the first follow-up. The causes of death were similar to the causes of death in the population at large.
Among the 16 probands and 26 affected relatives, 5 had a cancer, all outside the nervous system. For the entire cohort, the age at cancer diagnosis was significantly younger among individuals with NF1 occurring primarily in childhood and adolescence.
But by adulthood, the incidence of cancer had leveled off, Dr. Sorensen said.
The excess cancer rate in childhood involved cancer of the nervous system, brain, and peripheral nerves, Dr. Mulvihill said.
“This is an important study,” he said. “The picture isn't as bad as people thought. When doctors talk with a couple about what lies ahead for them, they don't want to paint a picture that is overly grim.”
“What is new is that the excess rate of cancer is confined to a young age,” Dr. Mulvihill said. “Kids and adolescents with NF1 have excess cancer, but after that, the cancer rate approaches that of the average population.”