About 5–10% of pancreatic cancers have been linked to an underlying genetic disorder, usually inherited in an autosomal dominant manner. We have previously studied the risk of cancer in patients with cystic fibrosis and found that, although the overall risk of cancer was not increased, there was a fivefold increase in the risk of digestive tract cancer.1,2 Because only four patients developed pancreatic cancer, it was difficult to estimate the risk accurately. Since the publication of these reports we have obtained information on additional patients with both cystic fibrosis and pancreatic cancer from the US cystic fibrosis patient registry, from published reports, and by querying surgeons, pathologists, and cystic fibrosis physicians in the USA, Canada, and Europe.
We now describe nine patients with cystic fibrosis and pancreatic cancer identified during the study period (1985 to 2006), including four from our original reports (table 11).). Based on age, sex, race, and calendar‐year‐specific incidence rates obtained from the Surveillance, Epidemiology, and End Results (SEER) programme, we previously estimated the number of expected pancreatic cancers in the USA cystic fibrosis population (n=28 858) for the 10 year period 1990 to 1999 to be 0.4.2 Assuming that the cystic fibrosis population in Europe is approximately equal to that in the USA, then the expected number of pancreatic cancers in the combined USA and European populations during the period 1985 to 2005 is 1.7, yielding a risk ratio of 5.3 (95% confidence interval, 2.4 to 10.1).
There were four women and five men with a median age of 35 years (range 18 to 58). Five patients had known cystic fibrosis mutations: four were ΔF508 homozygotes and one was a ΔF508 heterozygote. Five patients had pancreatic exocrine insufficiency, five had mild or moderate lung disease, and two had potential risk factors that might have increased their risk of pancreatic cancer. One patient had received six years of immunosuppressive treatment following lung transplantation before developing pancreatic cancer; this patient had also received growth hormone for three years. Another patient developed pancreatic mucinous cystadenocarcinoma in a cyst that had been present for 13 years.
The increased relative risk of pancreatic cancer in the cystic fibrosis population compared with the general population is an age related finding: pancreatic cancer is rare in younger individuals. However, although we observed an excess risk of pancreatic cancer within the cystic fibrosis population compared with the background population, we were able to identify only nine patients in North America and Europe over a 21 year period. This translates into an incidence of approximately 1/100 000/year (nine pancreatic cancers in 1.2 million person‐years). Therefore, although the relative risk is increased, the chance of any single cystic fibrosis patient developing pancreatic cancer is extremely low. Physicians who treat cystic fibrosis patients are unlikely ever to encounter one with pancreatic cancer. However, as the life span of people with cystic fibrosis increases, the absolute risk of pancreatic and other types of digestive tract cancer is likely to increase. At present, screening cystic fibrosis patients for this cancer or other gastrointestinal tumours is not indicated.
As there is an excess risk of early onset pancreatic cancer in patients with cystic fibrosis, perhaps other modifying genes or environmental factors are important. Mucin genes, which are found in both cystic fibrosis and pancreatic cancer, may be important.10 Patients with cystic fibrosis can have nutritional deficiencies, another possible risk factor for cancer.
Although case ascertainment in the USA relies on a national cystic fibrosis registry and is likely to be complete, it is possible that we missed some cases of pancreatic cancer in the European cystic fibrosis patients. This potential deficit would be limited, as similar numbers of cases were reported in the USA and Europe, which have populations of roughly similar size.
In summary, the estimated risk of pancreatic cancer in cystic fibrosis is five to six times greater than in the general population, but compared with other causes of mortality, the absolute risk of pancreatic cancer in patients with cystic fibrosis is negligible.