New research published in Cell Reports has revealed that high levels of iron switches on a key pathway in people with faults in a critical anti-cancer gene (APC) that could raise the risk of bowel cancer.
According to Cancer Research UK scientists, based at the University of Birmingham and the Beatson Institute for Cancer Research in Glasgow, bowel cancers were 2 to 3 times more likely to form in mice fed high amounts of iron with a faulty APC gene, compared to mice who still had a fully functioning APC gene. However, mice with the faulty gene that were fed very low amounts of iron did not develop bowel cancer at all.
Bowel cancer, or colorectal cancer, can occur in either the small or large bowel (also known as the small or large intestine). Symptoms of this disease may go unnoticed for a long time, so it is important to get your health checked regularly. Fortunately if diagnosed early, it is often curable. It is recommended for people over the age of 50 to have a screening for bowel cancer every 2 years. A few symptoms include constant fatigue, unexplainable weight loss, blood or mucus in the faeces, bloating, and cramps.
Professor Owen Sansom, study author and deputy director of the Cancer Research UK Beatson Institute for Cancer Research in Glasgow, explained:
“We’ve made a huge step in understanding how bowel cancer develops. The APC gene is faulty in around 8 out of 10 bowel cancers but until now we haven’t known how this causes the disease.
It’s clear that iron is playing a critical role in controlling the development of bowel cancer in people with a faulty APC gene. And, intriguingly, our study shows that even very high levels of iron in the diet don’t cause cancer by itself, but rely on the APC gene.”
Dr. Chris Tselepis, a Cancer Research UK scientist at the University of Birmingham and study co-author, said:
“Our results also suggest that iron could be raising the risk of bowel cancer by increasing the number of cells in the bowel with APC faults. The more of these cells in the bowel, the greater the chance that one of these will become a starting point for cancer.”
The experts plan to develop treatments that decrease the amount of iron in the bowel in order to reduce the chances of developing bowel cancer, Tselepis added. After a few years, they hope their treatments will be ready for trials in people who are at a higher risk.
The finding could also suggest why red meats, and other foods high in iron, are linked to an increased risk of bowel cancer.
Two proteins become turned on, when the APC gene is deleted, which results in a build up of iron in bowel cells. When this occurs, wnt (a key cancer signaling pathway) is turned on, which results in cells growing out of control.
Results showed that bowel cancers did not form in mice that were given no iron in their diet, and the cells with a faulty APC gene were killed.
When mice that had a working APC gene were given a diet high in iron, they did not develop bowel cancers. In their bowel cells, the iron accumulation proteins were turned off and wnt signaling remained inactive.
Dr. Julie Sharp, senior science information manager at Cancer Research UK, concluded, “Bowel cancer is the third most common cancer in the UK. These findings suggest a potentially effective way of reducing the chances of bowel cancer developing in people who are at high risk. Finding ways of ‘mopping up’ the iron that is in the bowel could have a real impact on the number of people who develop the disease.”
She also added that their study is a great example of a group of scientists sharing their different expertise in order to find new ways of understanding cancer and hopefully finding ways to prevent it.
Written by Sarah Glynn