London | A Western-style diet rich in fat and low in fibre, vitamin D and folate may lead to the development of colorectal cancer, a new study has warned. Colorectal cancer is the second most common cause of cancer-related deaths in the western world, mainly because it is usually diagnosed too late, researchers said.
Interactions between genetic and environmental factors, including diet, are thought to play a crucial role in its development, but the earliest changes in normal colonic mucosa that could lead to early detection and prevention of cancer development remains to be made clear, they said.
Using a mouse model of Lynch syndrome, the most common form of inherited colon cancer, researchers from University of Helsinki in Finland carried out a long-term diet experiment. The Lynch syndrome mouse carries a mutation in MIh1, a mismatch repair gene, which is one of the main susceptibility genes in the disease.
Each time cells divide, DNA has to replicate itself. It is during this process that mistakes can be made, leading to genomic instability and potentially to cancer, researchers said. Lynch syndrome carriers have inherited one healthy and one mutated mismatch repair gene, and about an 80 per cent risk of developing cancer, researchers said.
We wanted to be able to spot cancer-predicting events in the colon mucosa before tumours developed, said Marjaana Pussila from University of Helsinki. For this reason, we decided to use a mouse model which was already known to have a susceptibility to colon cancer, said Pussila.
We reasoned that in mutation carriers requiring just a second hit of the inherited susceptibility gene for malignant transformation, it might be possible to detect the earliest changes, perhaps even preceding the second hit and distinguish these from alterations occurring later in cancer development, she added.
The results showed that the gene expression profiles of normal mucosa in those mice that developed colon cancer were very different from those of the mice that did not, researchers said. This seems to indicate that there is a colon-wide effect of events that predispose to cancer.
And the Western-style diet seemed to be a severe risk factor, since 80 per cent of cancers were detected in Western-style fed mice, said Pussila. No typical Lynch syndrome tumour characteristics, such as lack of MIh1 protein or microsatellite instability – a kind of genetic hyper-mutability – were detected, although MIh1 gene expression was already severely decreased in the mucosa, researchers said.
This suggests that a decrease in MIh1 gene expression may be sufficient to induce the development of tumours, even where the DNA mismatch repair mechanism that recognises and corrects mistakes in DNA replication is still operating well enough to avoid microsatellite instability, they said.
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