London: A typical Western-style diet that is rich in fat and low in fibre, vitamin D and folic acid is likely to play a major role in the development of colorectal cancer, reveals a new study. Colorectal cancer, the second most common cause of cancer-related deaths, is due to the abnormal growth of cells that have the ability to invade or spread to other parts of the body. The earliest changes in normal colonic mucosa — the first layer of the intestines where nutrients, fats and proteins are absorbed from the foods we eat — has the potential to lead to the early detection and prevention of cancer development, the researchers said.
“We wanted to be able to spot cancer-predicting events in the colon mucosa before tumours developed,” said Marjaa Pussila, doctoral student at the University of Helsinki in Finland.
For the study, the team carried out a long-term diet experiment on genetically engineered mice model affected with Lynch syndrome — the most common form of inherited colon cancer.
The mouse with Lynch syndrome carries a mutation in MIh1, a mismatch repair gene, which is one of the main susceptibility genes in the disease.
Each time cells divide, D replicates itself. It is during this process that mistakes can be made, leading to genomic instability and potentially to cancer.
The findings 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.
“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 percent of cancers were detected in such mice,” Pussila added.
Further, 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.
This suggests that a decrease in MIh1 gene expression may be sufficient to prompt the development of tumours, even where the D mismatch repair mechanism that recognises and corrects mistakes in D replication is still operating well enough to avoid microsatellite instability.
It has been generally assumed that the development of cancer in Lynch syndrome carriers needs an ictivation of both the mismatch repair genes or pairs, involved, thus causing microsatellite instability.
However, “our studies have shown that this is not necessarily the case, since a severely decreased amount of MIh1 without loss of the mismatch repair gene and without microsatellite instability appears to be enough to provoke the development of tumours,” Pussila explained.
“Now, by studying the gene expression profiles of Mlh1 low mucosa we hope to be able to further identify cancer predisposing changes which may help in the early detection of tumours,” Pussila noted. (IANS)