Bowel Cancer Linked to High Dietary Iron and Defective Gene Function

The combination of high dietary iron content and defective functioning of the APC (adenomatous polyposis coli) gene has been found to increase the risk of developing bowel cancer significantly.

The APC gene encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. It is also involved in other processes including cell migration and adhesion, transcriptional activation, and apoptosis. Defects in this gene cause familial adenomatous polyposis (FAP), an autosomal dominant premalignant disease that usually progresses to malignancy.

Investigators at the University of Birmingham (United Kingdom) and the Beatson Institute for Cancer Research (Glasgow, United Kingdom) published a study in the August 9, 2012, online edition of the journal Cell Reports that linked APC mutations and high dietary iron content to the development of bowel cancer.

They showed in a mouse model system that after APC deletion the cellular iron acquisition proteins TfR1 and DMT1 were rapidly induced. Conversely, restoration of APC reduced cellular iron due to repression of these proteins. To test the functional importance of these findings, they performed in vivo investigations of the impact of iron levels on intestinal tumor development. Strikingly, depletion of luminal (but not systemic) iron strongly suppressed tumor development in intestines of the mice, whereas increased luminal iron strongly promoted tumor development.

Bowel cancers were two to three times more likely to develop in mice with a faulty APC gene that were fed high amounts of iron compared to mice with a fully functioning APC gene. In contrast, mice with a faulty APC gene fed a diet low in iron did not develop bowel cancer at all.

Senior author Dr. Owen Sansom, deputy director of the for cancer research at the Beatson Institute for Cancer Research, said, "We have made a huge step in understanding how bowel cancer develops. The APC gene is faulty in around eight out of 10 bowel cancers but until now we have not known how this causes the disease. It is 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 do not cause cancer by itself, but rely on the APC gene."

Results obtained during this study could explain why foods such as red meat, which have high levels of iron, are linked to an increased risk of bowel cancer.

Related Links:
University of Birmingham
Beatson Institute for Cancer Research