FaCD Online Syndrome Fact Sheet

Last updated: 21 Feb 2008

Name: Cystic Fibrosis

Synonym: CF

Mode of Inheritance: AR

Genes

CFTR, mapped to 7q22.3-q23.1

Tumor features

esophageal cancer
nasal polyps
small intestinal cancer

Tumor features (possible)

leukemia, acute lymphoblastic (ALL)
leukemia, acute myeloid (AML, incl. ANLL)
pancreatic adenocarcinoma

Non-tumor features

aplasia of the vas deferens
biliary cirrhosis
esophagus, Barrett
lung emphysema
meconium ileus
pancreatic exocrine insufficiency

Comment

This disorder is cause by a chloride channel defect. Main clinical features are meconium ileus, lung emphysema and chronic respiratory infections, pancreatic fibrosis, biliary fibrosis, vas deferens aplasia and high sweat electrolytes.

A number of studies have studied the occurrence of cancer in CF patients and their relatives. Neglia et al.[1] did not observe a significantly increased cancer risk in a series of 712 CF patients, but could not exclude an increased risk in relatively old CF patients. In an additional study, Neglia et al.[2] studied the occurrence of cancer in 28,511 CF patients and concluded that, although the overall risk of cancer in CF is similar to that of the general population, there is an increased risk of digestive tract cancers. Sheldon et al.[3] studied a cohort of 412 CF patients and observed a greater than expected number of cases with pancreatic cancer and adenocarcinoma of the terminal ileum. In a survey of 24,500 European CF patients, Schöni et al.[4] observed a high relative risk (RR) for digestive tract cancer (RR 6.4), similar to that in the 2nd study of Neglia et al.[2]. Colon cancer in a 13-year-old boy with CF has been reported[17]. Possibly, the risk for pancreatic cancer in long term survivors is increased[18]

Although acute lymphoblastic leukemia has been reported in several CF patients[5-8], the CF patient population studies do not confirm a suspected increased acute leukemia risk. Robertson and Hawkins[9] did not observe an excess of CF patients in the British national registry of childhood tumors. Brown et al.[10] speculated that CF patients are more susceptible to oxidative (free radical)-cell injury due to impaired absorption of dietary-antioxidants and increased recurrent pulmonary infection, which results in increased number of pulmonary neutrophils (a major source of free radicals). They observed an increased amount of free radical induced DNA damage in CF patients, although there was no correlation with the severity of pulmonary dysfunction. The authors suggest that the increased DNA damage may explain increased cancer risks in CF patients.

Cancer risk in carriers
Several studies have looked at cancer rates in carriers (i.e. heterozygotes) of the CF gene mutation and/or relatives of CF patients (not necessarily CF heterozygotes). Warren et al.[11] did not find an increased frequency of carriers of the CF gene among patients with myeloid malignancy. However they did observe a lower than expected number of melanomas, which they later confirmed in a expansion of their first study[12]. There was a suggestion of lower colon cancer rates. Al-Jader et al.[13;14] observed a higher than expected number of CF patient's parents who died of leukemia, especially AML. They did not observe an excess of leukemia in the CF patients. Abraham et al.[15] found that heterozygous and homozygous CF mice had elevated blood ATP concentrations, associated with decreased breast cancer growth rate, suggesting an advantage in CF patients and carriers with respect to breast cancer. Southey et al.[16] observed similar numbers of breast cancer cases diagnosed before the age of 40 in carriers of the frequent deltaF508 CF mutation and controls. Contrary to the predictions all CF heterozygote associated breast cancers were found to be grade III (poorly differentiated).

Links

Cystic Fibrosis Foundation 18 1 08
Cystic Fibrosis Research Inc. (CFRI) 18 1 08
Cystic Fibrosis Trust 18 1 08

References

[1] Neglia JP, Wielinski CL, Warwick WJ. Cancer risk among patients with cystic fibrosis. J Pediat 1991; 119(5):764-766.
[2] Neglia JP, Fitzsimmons SC, Maisonneuve P, Schoni MH, Schoni-Affolter F, Corey M, Lowenfels AB, Boyle P, Dozor AJ, Durie P. The risk of cancer among patients with cystic fibrosis. N Engl J Med 1995; 332:494-499.
[3] Sheldon CD, Hodson ME, Carpenter LM, Swerdlow AJ. A cohort study of cystic fibrosis and malignancy. Br J Cancer 1993; 68(5):1025-1028.
[4] Schoni MH, Maisonneuve P, Schoni-Affolter F, Lowenfels AB. Cancer risk in patients with cystic fibrosis: The European data. J.R.Soc.Med. 89, 38-43. 1996.
[5] Rizzari C, Conter V, Jankovic M, D'Angelo P, Masera G, Costantini D, Bettinelli ME, Giunta AM. Acute lymphoblastic leukaemia in a child with cystic fibrosis. Haematologica 1992; 77(5):427-429.
[6] Gururangan S, Horner M, Rodman JH, Marina NM. Successful treatment of acute lymphoblastic leukemia in a child with cystic fibrosis [see comments]. Med Pediatr Oncol 1994; 22(6):414-416.
[7] Rizzari C, Conter V. "Childhood ALL and cystic fibrosis--treatment and outcome" [letter; comment]. Med Pediatr Oncol 1995; 25(3):223.
[8] Biggs BG, Vaughan W, Colombo JL, Sanger W, Purtilo DT. Cystic fibrosis complicated by acute leukemia. Cancer 1986; 57(12):2441-2443.
[9] Robertson CM, Hawkins MM. Childhood cancer and cystic fibrosis [letter]. J Natl Cancer Inst 1995; 87(19):1486-1487.
[10] Brown RK, Mcburney A, Lunec J, Kelly FJ. Oxidative damage to DNA in patients with cystic fibrosis. Free Radical Biol Med 1995; 18:801-806.
[11] Warren N, Holmes JA, Al-Jader L, West RR, Lewis DC, Padua RA. Frequency of carriers of cystic fibrosis gene among patients with myeloid malignancy and melanoma. BMJ 1991; 302(6779):760-761.
[12] Padua RA, Warren N, Grimshaw D, Smith M, Lewis C, Whittaker J, Laidler P, Wright P, Douglas-Jones A, Fenaux P, Sharma A, Horgan K, West R. The cystic fibrosis delta F508 gene mutation and cancer. Hum Mutat 1997; 10(1):45-48.
[13] Al-Jader LN, West RR, Goodchild MC, Harper PS. Mortality from leukaemia among relatives of patients with cystic fibrosis. BMJ 1989; 298(6667):164.
[14] Al-Jader LN, West RR, Holmes JA, Meredith L, Goodchild MC, Harper PS. Leukaemia mortality among relatives of cystic fibrosis patients. Arch Dis Child 1991; 66(3):317-319.
[15] Abraham EH, Vos P, Kahn J, Grubman SA, Jefferson DM, Ding I, Okunieff P. Cystic fibrosis hetero- and homozygosity is associated with inhibition of breast cancer growth. Nat Med 1996; 2(5):593-596.
[16] Southey MC, Batten L, Andersen CR, McCredie MRE, Giles GG, Dite G, Hopper JL, Venter DJ. CFTR Delta F508 carrier status, risk of breast cancer before the age of 40 and histological grading in a population-based case- control study. Int J Cancer 79[5], 487-489. 1998.
[17] Ibele AR, Koplin SA, Slaughenhoupt BL, Kryger JV, Friedl A, Lund DP. Colonic adenocarcinoma in a 13-year-old with cystic fibrosis. Journal of pediatric surgery 2007; 42(10):E1-3.
[18] Krysa J, Steger A. Pancreas and cystic fibrosis: the implications of increased survival in cystic fibrosis. Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 2007; 7(5-6):447-50.