Mobile Menu

Bowel cancer causing mutation identified

New research has identified an inherited mutated gene that is linked to an increased risk of developing bowel cancer. The findings could help produce a blood test that predicts colorectal cancer risk.

The study, published in Nature Communications, found that inherited mutations in the MUTYH gene were linked to an increased mutation rate in healthy tissues. The MUTYH gene repairs oxidative DNA damage and is involved in making the enzyme MYH glycosylase.

Researchers from the Wellcome Sanger Institute, Cardiff University and collaborators, discovered that individuals with two mutated copies of the gene, one from each parent, had raised mutation rates in healthy intestine cells. These then caused pre-cancerous growths with an even higher number of mutations.

“By gaining a deeper understanding about these processes, it may help us to predict the risk of colorectal cancer in those living with this genetic condition and potentially identify treatments for at-risk individuals,” noted one of the authors, Dr Phil Robinson from the Wellcome Sanger Institute.

Bowel cancer

Bowel cancer is the third most common cancer in the world. There were more than 1.9 million new cases of bowel cancer in 2020. While a range of different factors can cause cancer, some hereditary mutations can lead to a predisposition of developing disease.

The MUTYH gene is engaged in the DNA repair pathway following oxidative damage. Inherited mutations in the MUTYH gene lead to MUTYH-associated polyposis (MAP). MAP results in polyps in the large intestine and an elevated risk of early onset colorectal cancer.

The progression from inherited mutations in the MUTYH gene to the development of bowel cancer is not fully understood.

Extreme rates of mutation

The researchers studied intestinal tissues and blood from 10 patients with MAP. They discovered significantly elevated mutation rates in the healthy intestinal cells. At one extreme, a sixteen year old with MAP had the same number of mutations in his healthy intestinal tissues as would be expected if someone without MAP syndrome had lived to 455 years old.  

They team observed an increased mutation rate in peripheral blood cells, which are those circulating in the blood. The rate of mutations between intestinal cells and blood cells was positively correlated, suggesting that one day this might be used to stratify bowel cancer risk through a blood test.

The research also found mutation rates were modestly increased in blood cells from affected individuals. However, these are not known to be linked to any increase in risk of blood cancer development, suggesting that there may be other factors or mechanisms protecting these tissues.

The authors noted that further research is needed to shed light on why the bowel is particularly susceptible to cancers in this condition, and if there are ways to target the MUTYH mutation or the downstream mutations in the development of new treatments.

Professor Julian Sampson, author and Professor of Medical Genetics at the University of Cardiff, said, “This research represents an important step in understanding cancer development in people affected by MAP and also helps to explain why cancer risks vary between different people with MAP, paving the way for a more personalised approach to cancer surveillance.”

Written by Poppy Jayne Morgan, Front Line Genomics

Image Credit: Canva

More on these topics

Cancer / Colorectal / inheritance / Mutations / Prediction