Cancer Risk in Cystic Fibrosis: A 20-Year Nationwide Study From the United States

Maisonneuve, Patrick; Marshall, Bruce C.; Knapp, Emily A.; Lowenfels, Albert B.

doi:10.1093/jnci/djs481

Cited by 255 publications

(286 citation statements)

References 20 publications

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“…62,63 The fact that elevated expression of the Mirc1/Mir17-92 cluster is associated with several types of malignancies, and our findings that this cluster is elevated in CF patients, raises growing concerns about cancer predispositions in the CF population. 29,64,65 Current strides in research aim to prolong and improve the life of CF patients, however CF patients are prone to different types of cancers later in life.…”

Section: Discussionmentioning

confidence: 89%

“…29,64,65 Current strides in research aim to prolong and improve the life of CF patients, however CF patients are prone to different types of cancers later in life. 62,65,66 Elevated expression of the Mirc1/ Mir17-92 cluster in CF may contribute to this predisposition. It has also been shown that the Mirc1/Mir17-92 cluster is highly expressed in intestinal tissue in CF patients.…”

Section: Discussionmentioning

confidence: 99%

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Elevated Mirc1/Mir17-92 cluster expression negatively regulates autophagy and CFTR (cystic fibrosis transmembrane conductance regulator) function in CF macrophages

et al. 2016

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Cystic fibrosis (CF) is a fatal, genetic disorder that critically affects the lungs and is directly caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, resulting in defective CFTR function. Macroautophagy/autophagy is a highly regulated biological process that provides energy during periods of stress and starvation. Autophagy clears pathogens and dysfunctional protein aggregates within macrophages. However, this process is impaired in CF patients and CF mice, as their macrophages exhibit limited autophagy activity. The study of microRNAs (Mirs), and other noncoding RNAs, continues to offer new therapeutic targets. The objective of this study was to elucidate the role of Mirs in dysregulated autophagy-related genes in CF macrophages, and then target them to restore this host-defense function and improve CFTR channel function. We identified the Mirc1/Mir17-92 cluster as a potential negative regulator of autophagy as CF macrophages exhibit decreased autophagy protein expression and increased cluster expression when compared to wild-type (WT) counterparts. The absence or reduced expression of the cluster increases autophagy protein expression, suggesting the canonical inverse relationship between Mirc1/Mir17-92 and autophagy gene expression. An in silico study for targets of Mirs that comprise the cluster suggested that the majority of the Mirs target autophagy mRNAs. Those targets were validated by luciferase assays. Notably, the ability of macrophages expressing mutant F508del CFTR to transport halide through their membranes is compromised and can be restored by downregulation of these inherently elevated Mirs, via restoration of autophagy. In vivo, downregulation of Mir17 and Mir20a partially restored autophagy expression and hence improved the clearance of Burkholderia cenocepacia. Thus, these data advance our understanding of mechanisms underlying the pathobiology of CF and provide a new therapeutic platform for restoring CFTR function and autophagy in patients with CF.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Elevated Mirc1/Mir17-92 cluster expression negatively regulates autophagy and CFTR (cystic fibrosis transmembrane conductance regulator) function in CF macrophages

et al. 2016

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“…Other less well-defined but emerging complications may well become common in the future care for adults living into their fourth decade and beyond. Gastro-intestinal cancers are more common in adults with CF, with the most prevalent being colorectal cancers [17,18]. The metabolic consequences of being overweight or obese with CF are unclear; however, as adults live longer and potentiator and corrector therapy increases body mass index, problems with obesity may become an issue [19].…”

Section: Complexity Of Adult Cf Carementioning

confidence: 99%

Report of the European Respiratory Society/European Cystic Fibrosis Society task force on the care of adults with cystic fibrosis

et al. 2015

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The improved survival in people with cystic fibrosis has led to an increasing number of patients reaching adulthood. This trend is likely to be maintained over the next decades, suggesting a need to increase the number of centres with expertise in the management of adult patients with cystic fibrosis. These centres should be capable of delivering multidisciplinary care addressing the complexity of the disease, in addition to addressing the psychological burden on patients and their families. Further issues that require attention are organ transplantation and end of life management.Lung disease in adults with cystic fibrosis drives most of the clinical care requirements, and major lifethreatening complications, such as respiratory infection, respiratory failure, pneumothorax and haemoptysis, and the management of lung transplantation require expertise from trained respiratory physicians. The taskforce therefore strongly reccommends that medical leadership in multidisciplinary adult teams should be attributed to a respiratory physician adequately trained in cystic fibrosis management.The task force suggests the implementation of a core curriculum for trainees in adult respiratory medicine and the selection and accreditation of training centres that deliver postgraduate training to the standards of the HERMES programme. @ERSpublications Respiratory physicians, trained in adult CF management, should lead multidisciplinary teams taking care of patients http://ow.ly/SgRgj

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“…The study by Maisonneuve et al (2) was based on data from the US Cystic Fibrosis Foundation (CFF) Patient Registry for the period from 1990 to 2009, which is representative of the whole CF population, and includes approximately 85% of patients receiving care at one of the 120 CFF-accredited care centers in the United States. Due to confidentiality issues and the switch to medical electronic records, cancer case ascertainment was, however, incomplete for the period from 2000 to 2009.…”

Section: Risk Of Colorectal Cancer After Solid Organ Transplantationmentioning

confidence: 99%

Risk of Colorectal Cancer After Solid Organ Transplantation in the United States

Maisonneuve

Lowenfels

Marshall

2016

American Journal of Transplantation

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Cancer Risk in Cystic Fibrosis: A 20-Year Nationwide Study From the United States

Abstract: The overall burden of cancer in CF patients remains low; however they have an increased risk of digestive tract cancer, particularly following transplantation. They also have increased risk of lymphoid leukemia and testicular cancer, and decreased risk of melanoma.

Cited by 255 publications

References 20 publications

Elevated Mirc1/Mir17-92 cluster expression negatively regulates autophagy and CFTR (cystic fibrosis transmembrane conductance regulator) function in CF macrophages

Elevated Mirc1/Mir17-92 cluster expression negatively regulates autophagy and CFTR (cystic fibrosis transmembrane conductance regulator) function in CF macrophages

Report of the European Respiratory Society/European Cystic Fibrosis Society task force on the care of adults with cystic fibrosis

Risk of Colorectal Cancer After Solid Organ Transplantation in the United States

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