De inflammatoire darmziekten en darmkanker (colorectale kanker)

De inflammatoire darmziekten (IBD) zoals de ziekte van Crohn (CD) en colitis ulcerosa (UC), chronische inflammatoire aandoeningen van de darm. De prevalentie in de Verenigde Staten meer dan 200 gevallen per 100.000, het aantal IBD patiënten tussen 1 en 1,5 miljoen. CD invloed kunnen alle delen van het maagdarmkanaal, van mond tot anus, maar meestal gaat het distale deel van de dunne darm of ileum en colon. UC resulteert in dikke ontsteking die kunnen de rectum alleen of kan ontwikkelen tot proximaal deel van of het gehele colon betrekken. Klinische symptomen zijn diarree, buikpijn, gastro-intestinale bloeding, en gewichtsverlies. Een ernstige langdurige complicatie van chronische ontsteking is de ontwikkeling van colorectale kanker. Een genetische basis voor IBD had al lang erkend op basis van de toegenomen familiale risico. Echter, belangrijke discordantie voor CD bij tweelingen, en een veel minder robuust fenotypische concordantie voor UC, stelde bijkomende factoren een rol spelen bij de ziekte van pathogenese, met inbegrip van milieu-factoren. In de afgelopen jaren, is de vooruitgang in het begrijpen van de moleculaire basis van IBD versneld, te beginnen met het genereren van dierlijke modellen van colitis en kan ontwikkelen tot de identificatie van specifieke genetische merkers van kandidaat-gen, gen koppeling, en genoom-brede associatie-analyses. Genetische studies hebben ook geleid tot de erkenning van het belang van milieu-factoren, met name de cruciale rol van de darmflora in de CD en UC. Altered immuunrespons op de normale darmflora zijn de belangrijkste factoren bij IBD pathogenese. In dit onderzoek onderwerp, de genetische basis van IBD, zal de genetische en cellulaire veranderingen geassocieerd met colitis-geassocieerde darmkanker, en de opkomende rol van de intestinale microbiota en andere omgevingsfactoren worden beoordeeld.

Test to predict intestinal inflammation

A blood test may be able to predict whether people will get chronic intestinal inflammation. That is the conclusion of researchers at the University Medical Center (UMC) Utrecht. Their work is published in the journal Gut. The blood test can detect people at high risk of developing the
condition, for example in families of patients with chronic intestinal inflammation.
In this study, scientists from Utrecht extracted data from the major 350,000-strong European EPIC study. The EPIC researchers have produced a picture of the habits and the health of the participants. Because intestinal inflammation was not recorded in EPIC from the outset, a great deal of
detective work was needed to find patients with intestinal inflammation. Fiona van Schaik, a graduate student and trainee gastrointestinal and liver specialist, searched the Dutch part of EPIC for patients with chronic intestinal inflammation. The researchers tracked down a total of 244
patients with Crohn’s disease or ulcerative colitis.

Five times the risk
Fiona van Schaik and her colleagues were then able to link the concentrations of four antibodies in the blood to chronic intestinal inflammation. It was possible to use these blood values to predict the risk of a healthy person developing chronic intestinal inflammation. A positive test result
means that the risk is over five times higher than the average. The results were published online in the journal Gut on July 27.

The test does not seem suitable for screening the entire population. Ms. Van Schaik and colleagues have set the test up so as not to generate too many false positives, although it does then miss future patients somewhat more often. This means that the test is above all useful for checking
people who have a high risk of chronic intestinal inflammation. These are mostly the direct family members of patients.

Preventive treatments
“At UMC Utrecht, we want to test patients’ family members so that we can investigate how chronic intestinal inflammations develop,” explains Ms. Van Schaik. “We know that heredity and nutrition are contributory factors, but we don’t really understand exactly how the illnesses arise. This will
also let us test preventive treatments that might be able to prevent the disease or alleviate it.” Ms. Van Schaik is the article’s lead author. She will be receiving her degree in November 2012 for her work on chronic intestinal diseases. Dr. Bas Oldenburg is her supervisor; he is a
gastrointestinal and liver specialist.

About 55,000 people in the Netherlands suffer from Crohn’s disease or ulcerative colitis. The severity of the condition varies a great deal from one person to the next, but it can mean that patients lose portions of their intestine. The patients also have a higher risk of intestinal cancer.
Treatment consists of anti-inflammatory drugs.

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