A cohort study of cystic fibrosis and malignancy

Sheldon, C.D.; Hodson, M E; Carpenter, LM; Swerdlow, Anthony

doi:10.1038/bjc.1993.474

Cited by 80 publications

(46 citation statements)

References 15 publications

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“…Also, there has been a concern about the risk of various cancers in CF patients and carriers of CFTR mutations (Malats et al, 2001). While a protective role of CFTR has been predicted for breast cancer and melanoma (Warren et al, 1991;Abraham et al, 1996), a significant excess of digestive tract cancer in CF patients has also been reported (Sheldon et al, 1993;Neglia et al, 1995). In the present study, we observed a reduced/negligible expression of CFTR in most (81%) pancreatic cancer cell lines, while it was expressed in cultured pancreatic ductal cells and normal pancreas ( Figure 1a).…”

Section: Discussionmentioning

confidence: 99%

MUC4 expression is regulated by cystic fibrosis transmembrane conductance regulator in pancreatic adenocarcinoma cells via transcriptional and post-translational mechanisms

et al. 2006

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MUC4 mucin is a high molecular weight transmembrane glycoprotein that plays important roles in tumour biology. It is aberrantly expressed in pancreatic adenocarcinoma, while not being detectable in the normal pancreas. Previous studies have demonstrated that the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel that is defective in CF, is implicated in multiple cellular functions, including gene regulation. In the present study, using a CFTR-defective pancreatic cancer cell line and its derived subline expressing functional CFTR, we report that MUC4 expression is negatively regulated by CFTR. Short-interfering RNA (siRNA)-mediated silencing of CFTR also leads to an increased expression of MUC4. Additionally, our results suggest that CFTR-mediated regulation of MUC4 is cell densitydependent and is achieved by transcriptional and posttranslational mechanisms. Moreover, in a panel of pancreatic cancer cell lines and normal pancreas, we observed that CFTR was downregulated in pancreatic cancer cells and negatively correlated with MUC4 in most cases. An aberrant expression of MUC4 was also detected in the CF pancreas. Downregulation of CFTR in pancreatic adenocarcinoma and its inverse association with the tumour-linked mucin, MUC4, indicate novel function(s) of CFTR in pancreatic tumour biology and suggest the implication of new signalling pathway(s) in MUC4 regulation.

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Section: Discussionmentioning

confidence: 99%

MUC4 expression is regulated by cystic fibrosis transmembrane conductance regulator in pancreatic adenocarcinoma cells via transcriptional and post-translational mechanisms

et al. 2006

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“…In 1993, Sheldon et al (21) reported a study among 412 subjects with CF and found two cases of pancreatic cancer [0.008 expected, P ϭ 0.001, odds ratio (OR) 61]. The increased incidence of digestive tract cancers, but not cancer in general, was then confirmed by Neglia et al (18) among 28,511 CF patients in the United States and Canada (risk ratio 6.5) and Europe (risk ratio 6.4).…”

Section: Cp Increases the Risk For Pancreatic Cancermentioning

confidence: 99%

Inflammation and Cancer V. Chronic pancreatitis and pancreatic cancer

Whitcomb

2004

American Journal of Physiology-Gastrointestinal and Liver Physi

177

125

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Pancreatic inflammation appears to increase the risk of pancreatic cancer. This observation is striking in the hereditary pancreatitis kindreds but also occurs in alcoholic, idiopathic, and tropical chronic pancreatitis and cystic fibrosis. However, the mutations associated with hereditary pancreatitis or cystic fibrosis are not found in sporadic pancreatic adenocarcinomas, suggesting that the effects are indirect by causing recurrent pancreatitis and chronic inflammation. The process of mutation accumulation and clonal expansion that is required for development of invasive pancreatic adenocarcinoma must therefore be accelerated in chronic pancreatitis to account for the high incidence of pancreatic cancer in these patients.

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“…Furthermore, intestinal transit is largely dependent on peristalsis (not ciliary activity), and may improve postnatally with compensatory changes in muscular tone or other physiological adaptations. Shortly after birth, the nonfunctional CFTR in CF significantly impairs airway mucociliary function in individuals who otherwise show normal humoral and cellular immunity with no evidence of increased susceptibility to viral infection or malignancy (Abraham et al, 1996;Dakin et al, 2002;Noah et al, 1997;Sheldon et al, 1993). Although tissue destruction and toxin production have long been viewed as characteristic traits of pseudomonal virulence, Pa is an environmentally ubiquitous saprophyte.…”

Section: Introductionmentioning

confidence: 99%

Chronic pulmonary pseudomonal infection in patients with cystic fibrosis: A model for early phase symbiotic evolution

Qin

2014

Critical Reviews in Microbiology

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To cite this article: Xuan Qin (2016) Chronic pulmonary pseudomonal infection in patients with cystic fibrosis: A model for early phase symbiotic evolution, Critical Reviews in Microbiology, 42:1, 144-157, DOI: 10.3109/1040841X.2014 AbstractGain of ''antimicrobial resistance'' and ''adaptive virulence'' has been the dominant view of Pseudomonas aeruginosa (Pa) in cystic fibrosis (CF) in the progressively damaged host airway over the course of this chronic infection. However, the pathogenic effects of CF airway-adapted Pa strains are notably reduced. We propose that CF Pa and other bacterial cohabitants undergo host adaptation which resembles the changes found in bacterial symbionts in animal hosts. Development of clonally selected and intraspecific isogenic Pa strains which display divergent colony morphology, growth rate, auxotrophy, and antibiotic susceptibility in vitro suggests an adaptive sequence of infective exploitation-parasitism-symbiotic evolution driven by host defenses. Most importantly, the emergence of CF pseudomonal auxotrophy is frequently associated with a few specific amino acids. The selective retention or loss of specific amino acid biosynthesis in CF-adapted Pa reflects bacterium-host symbiosis and coevolution during chronic infection, not nutrient availability. This principle also argues against the long-standing concept of dietary availability leading to evolution of essential amino acid requirements in humans. A novel model of pseudomonal adaptation through multicellular bacterial syntrophy is proposed to explain early events in bacterial gene decay and decreased (not increased) virulence due to symbiotic response to host defense.

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A cohort study of cystic fibrosis and malignancy

Abstract: On the basis of the present findings and previous case reports in the literature adenocarcinoma of the pancreas and adenocarcinoma of the terminal ileum may be associated with cystic fibrosis.

Cited by 80 publications

References 15 publications

MUC4 expression is regulated by cystic fibrosis transmembrane conductance regulator in pancreatic adenocarcinoma cells via transcriptional and post-translational mechanisms

MUC4 expression is regulated by cystic fibrosis transmembrane conductance regulator in pancreatic adenocarcinoma cells via transcriptional and post-translational mechanisms

Inflammation and Cancer V. Chronic pancreatitis and pancreatic cancer

Chronic pulmonary pseudomonal infection in patients with cystic fibrosis: A model for early phase symbiotic evolution

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