Colorectal cancer is the second most common cause of cancer-related deaths in the western world. This is mainly due to a late diagnosis.
Therefore, finding ways to identify those who are at an increased risk of developed colon cancer is crucial.
Researchers’ work in genetically-engineered mice has helped to reveal the role played by a Western-style diet, rich in fat and low in fiber, vitamin D and folate, in the development of colorectal cancer.
Researchers believe that interactions between genetic and environmental factors play a crucial role in the development of colorectal cancer.
The earliest changes in normal colonic mucosa that could lead to early detection and prevention of cancer development remain a mystery.
Using a mouse model of Lynch syndrome, researcher carried out a long-term diet experiment. Lynch syndrome is the most common form of inherited colon cancer.
The Lynch syndrome mouse carries a mutation in MIh1 which is one of the main susceptibility genes in the disease. Each time cells divide, DNA has to replicate itself. During this process mistakes can be made, leading to genomic instability and potentially to cancer.
Lynch syndrome carriers have inherited one healthy and one mutated mismatch repair gene and about an 80% risk of developing cancer.
The results of the study showed that the gene expression profiles of normal mucosa int hose mice that developed colon cancer were very different from those of the mice that did not. This indicates that there is a colon-wide effect of events that predispose to cancer.
According to researchers, the Western-style diet seemed to be a severe risk factor, since 80% of cancer were detected in Western-style diet fed mice.
It has been generally assumed that the development of cancer in Lynch syndrome carriers needs an inactivation of both the mismatch repair gene alleles, thus causing microsatellite instability. However, this study shows that this is not necessarily the case, since a severely decreased amount of NIh1 without loss of the second allele and without microsatellite instability appears to be enough to provoke the development of tumors.
Researchers how to be able to further identify cancer predisposing changes which could help in the early detection of tumors.
