764
Clinical and laboratory observations
The Journal of Pediatrics November 1991
Cancer risk among patients with cystic fibrosis Joseph P. Neglia, MD, MPH, Catherine L. Wielinski, Bs, a n d Warren J. Warwick, MD From the Department of Pediatrics, Divisions of Hematology/Oncology and Pulmonary Medicine, University of Minnesota School of Medicine, Minneapolis
Increased risks of cancer have been described with several constitutional disorders, including Down syndrome, neurofibromatosis, and many others. Speculation on whether cystic fibrosis should be added to this list is based in part on several case reports of cancer among persons with CF 112 and a report of an increased number of deaths from leukemia among family members of patients with C F J 3 The recent finding of the proximity of the CF gene to the met oncogene has added to interest in such a clinical association. As aggressive pulmonary therapies have increased the life expectancy of patients with CF, an inherited predisposition to malignancy, previously obscured by the short life span of these patients, may become evident.
of the patients were known to be dead and 348 were alive and in active follow-up; 210 patients had been transferred to another institution or lost to follow-up. Ages in the cohort at analysis ranged from 1 month to 51 years (median 13.8 years). Two cancers were identified. The first case was that of a stage I seminoma that occurred in a 32-year-old man. The second was in a 10-year-old boy who had clonus and hyperreflexia of the lower extremities; an intraspinal high-grade astrocytoma was found at laminectomy. At the time of analysis this cohort had accrued 10,622 person-years at risk. Application of the incidence rates of CF
METHODS A retrospective cohort of all patients with CF followed at the University of Minnesota Cystic Fibrosis Center from 1962 to April 1990 was constructed. The "at risk" period for the purpose of calculating the expected cancer occurrence was defined as the time from birth to the time of death, the most recent clinic visit, or the development of malignancy. Patients lost to follow-up or transferred to another center were censored at the time of their last clinic visit. The expected number of cancers among the cohort was determined by applying age-, gender-, and race-specific incidence rates from the Surviellance Epidemiology and End Results Program of the National Cancer Institute to the total person-years accumulated. The ratio of the observed cancers to the expected number was tested for statistical significance under the assumptions of a Poisson model. RESULTS Seven hundred twelve patients with CF were included in this retrospective cohort. At the time of this analysis, 154
Supported by funds from the Childrens Cancer Research Fund of the University of Minnesota and the Cystic Fibrosis Foundation. Dr. Neglia is a recipient of National Cancer Institute Clinical Investigator Award CA 01240. Submitted for publication Jan. 8, 1991; accepted May 17, 1991. Reprint requests: Joseph P. Neglia, MD, Box 484 UMHC, Harvard St. at E. River Rd., Minneapolis, MN 55455. 9/22/31045
Cystic fibrosis
[
the Surviellance Epidemiology and End Results Program to this distribution resulted in an expected number of 1.94 cases, yielding an observed/expected ratio of 1.03 (95% confidence intervals 0.12 and 3.71). DISCUSSION To date, several cases of cancer in patients with CF have been reported (Table). Many of these cancers have been of the gastrointestinal or hepatobiliary tract, often occurring at relatively young ages. In addition, six cases of leukemia have been reported, along with two neuroblastomas, one retinoblastoma, and two Wilms tumors. All these reports have been accompanied by concerns that patients with CF may be at increased risk of malignancy. Speculation regarding the source of this risk has included abnormalities of bile circulation, chloramphenicol exposure, 8 or a global predisposition to malignancy as a result of depletion of seleniu~ and vitamin E ) 4 By analogy, a markedly increased risk of small bowel adenocarcinoma exists in persons with celiac disease, a disorder also characterized by steatorrhea. 1~ Although the pathobiology of this increased risk in celiac disease is unknown, damage to the small bowel mucosa, rendering it more susceptible to environmental carcinogens, has been suggested. These reports, in aggregate, raise concerns regarding cancer risk in patients with CF, in part because of the early age at onset of the adenocarcinomas and the relative rarity of these cancers in the population at large.
Volume 119 Number 5
Clinical and laboratory observations
76$
Table. Reported malignancies in patients with CF Age/sex
Malignancy
Therapy
Outcome
23 yr/F
Pancreatic adenocarcinoma
None
26 yr/M
Pancreatic adenocarcinoma
Palliative surgery
42 yr/M
Pancreatic adenocarcinoma
Surgery Surgery
29 yr/M
Adenocarcinomaof the extrahepatic biliary system Adenocarcinoma of the ileum
30 yr/M 34 yr/M
Adenocarcinoma of the ileum Adenocarcinoma of the ileum
Not available Surgery
20 yr/M
Acute lymphocytic leukemia
Chemotherapy
25 yr/M
Acute nonlymphocyticleukemia
Chemotherapy
10 yr/M
Clinical and laboratory observations
The Journal of Pediatrics November 1991
Cancer risk among patients with cystic fibrosis Joseph P. Neglia, MD, MPH, Catherine L. Wielinski, Bs, a n d Warren J. Warwick, MD From the Department of Pediatrics, Divisions of Hematology/Oncology and Pulmonary Medicine, University of Minnesota School of Medicine, Minneapolis
Increased risks of cancer have been described with several constitutional disorders, including Down syndrome, neurofibromatosis, and many others. Speculation on whether cystic fibrosis should be added to this list is based in part on several case reports of cancer among persons with CF 112 and a report of an increased number of deaths from leukemia among family members of patients with C F J 3 The recent finding of the proximity of the CF gene to the met oncogene has added to interest in such a clinical association. As aggressive pulmonary therapies have increased the life expectancy of patients with CF, an inherited predisposition to malignancy, previously obscured by the short life span of these patients, may become evident.
of the patients were known to be dead and 348 were alive and in active follow-up; 210 patients had been transferred to another institution or lost to follow-up. Ages in the cohort at analysis ranged from 1 month to 51 years (median 13.8 years). Two cancers were identified. The first case was that of a stage I seminoma that occurred in a 32-year-old man. The second was in a 10-year-old boy who had clonus and hyperreflexia of the lower extremities; an intraspinal high-grade astrocytoma was found at laminectomy. At the time of analysis this cohort had accrued 10,622 person-years at risk. Application of the incidence rates of CF
METHODS A retrospective cohort of all patients with CF followed at the University of Minnesota Cystic Fibrosis Center from 1962 to April 1990 was constructed. The "at risk" period for the purpose of calculating the expected cancer occurrence was defined as the time from birth to the time of death, the most recent clinic visit, or the development of malignancy. Patients lost to follow-up or transferred to another center were censored at the time of their last clinic visit. The expected number of cancers among the cohort was determined by applying age-, gender-, and race-specific incidence rates from the Surviellance Epidemiology and End Results Program of the National Cancer Institute to the total person-years accumulated. The ratio of the observed cancers to the expected number was tested for statistical significance under the assumptions of a Poisson model. RESULTS Seven hundred twelve patients with CF were included in this retrospective cohort. At the time of this analysis, 154
Supported by funds from the Childrens Cancer Research Fund of the University of Minnesota and the Cystic Fibrosis Foundation. Dr. Neglia is a recipient of National Cancer Institute Clinical Investigator Award CA 01240. Submitted for publication Jan. 8, 1991; accepted May 17, 1991. Reprint requests: Joseph P. Neglia, MD, Box 484 UMHC, Harvard St. at E. River Rd., Minneapolis, MN 55455. 9/22/31045
Cystic fibrosis
[
the Surviellance Epidemiology and End Results Program to this distribution resulted in an expected number of 1.94 cases, yielding an observed/expected ratio of 1.03 (95% confidence intervals 0.12 and 3.71). DISCUSSION To date, several cases of cancer in patients with CF have been reported (Table). Many of these cancers have been of the gastrointestinal or hepatobiliary tract, often occurring at relatively young ages. In addition, six cases of leukemia have been reported, along with two neuroblastomas, one retinoblastoma, and two Wilms tumors. All these reports have been accompanied by concerns that patients with CF may be at increased risk of malignancy. Speculation regarding the source of this risk has included abnormalities of bile circulation, chloramphenicol exposure, 8 or a global predisposition to malignancy as a result of depletion of seleniu~ and vitamin E ) 4 By analogy, a markedly increased risk of small bowel adenocarcinoma exists in persons with celiac disease, a disorder also characterized by steatorrhea. 1~ Although the pathobiology of this increased risk in celiac disease is unknown, damage to the small bowel mucosa, rendering it more susceptible to environmental carcinogens, has been suggested. These reports, in aggregate, raise concerns regarding cancer risk in patients with CF, in part because of the early age at onset of the adenocarcinomas and the relative rarity of these cancers in the population at large.
Volume 119 Number 5
Clinical and laboratory observations
76$
Table. Reported malignancies in patients with CF Age/sex
Malignancy
Therapy
Outcome
23 yr/F
Pancreatic adenocarcinoma
None
26 yr/M
Pancreatic adenocarcinoma
Palliative surgery
42 yr/M
Pancreatic adenocarcinoma
Surgery Surgery
29 yr/M
Adenocarcinomaof the extrahepatic biliary system Adenocarcinoma of the ileum
30 yr/M 34 yr/M
Adenocarcinoma of the ileum Adenocarcinoma of the ileum
Not available Surgery
20 yr/M
Acute lymphocytic leukemia
Chemotherapy
25 yr/M
Acute nonlymphocyticleukemia
Chemotherapy
10 yr/M
