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Related Concept Videos

Cystic Fibrosis: Pathogenesis01:23

Cystic Fibrosis: Pathogenesis

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Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
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Cystic Fibrosis: Management01:24

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Cystic fibrosis (CF) is an autosomal recessive disorder that predominantly affects individuals of Northern European descent, occurring at a rate of 1 in 3500. It is caused by a genetic mutation in a gene on chromosome 7, most commonly the ΔF508 mutation, that codes for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. This results in thicker mucus secretions and obstruction pathologies in multiple organs, including the lungs and sinuses.
Sinus disease and chronic...
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Transcellular Transport of Solutes01:23

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Transcellular transport of solutes is the movement of substances like monosaccharides and amino acids through polarized cells. This transport mechanism is primarily seen in epithelial and endothelial cells aided by membrane transport proteins such as channels and transporters. The tight junctions between these cells confine the membrane proteins to the two sides of the cell. The epithelial cells have distinct apical and basolateral domains. In contrast, the endothelial cells show the luminal...
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Cystic Fibrosis, CFTR, and Colorectal Cancer.

Patricia Scott1, Kyle Anderson1, Mekhla Singhania1

  • 1Department of Biomedical Sciences, University of Minnesota Medical School, Duluth, MN 55812, USA.

International Journal of Molecular Sciences
|April 25, 2020
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Summary

Cystic fibrosis (CF) increases colorectal cancer (CRC) risk due to CFTR gene mutations. New guidelines recommend earlier CRC screening for CF patients and carriers, with potential for repurposed CF drugs in cancer treatment.

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CFTRcolorectal cancercystic fibrosistumor suppressor

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Area of Science:

  • Genetics and Oncology
  • Gastroenterology
  • Molecular Biology

Background:

  • Cystic fibrosis (CF), caused by CFTR gene mutations, is now recognized as a familial colorectal cancer (CRC) syndrome.
  • CF patients exhibit high susceptibility to early-onset, aggressive colorectal tumors, with significant adenoma and adenocarcinoma development by age 40.
  • This heightened risk extends to over 10 million US carriers of CFTR mutations and is linked to reduced CFTR expression in sporadic CRC.

Purpose of the Study:

  • To highlight the link between cystic fibrosis and increased colorectal cancer risk.
  • To discuss the implications for current and future CRC screening protocols in CF patients and carriers.
  • To explore potential therapeutic strategies, including drug repurposing, for CF-associated gastrointestinal cancers.

Main Methods:

  • Review of endoscopic screening studies in cystic fibrosis patients.
  • Analysis of genetic data regarding CFTR mutations and CRC risk.
  • Examination of molecular mechanisms implicated in CFTR's tumor suppressor role.

Main Results:

  • 50% of CF patients develop adenomas by age 40; 25% develop advanced adenomas or adenocarcinomas.
  • Lowered CFTR expression correlates with poor survival in sporadic CRC.
  • Dysregulation of Wnt/β-catenin signaling, stem cell homeostasis, and intestinal inflammation are implicated in CF-related tumorigenesis.

Conclusions:

  • CFTR gene mutations confer a significant predisposition to colorectal cancer, necessitating revised screening guidelines.
  • Understanding CFTR's tumor suppressor functions is crucial for developing targeted therapies.
  • Repurposing existing CF drugs may offer novel treatment avenues for gastrointestinal cancers in CF patients.