Diet could play a major role in colorectal cancer, leading geneticists will hear today (23 May, 2016).
Marjaana Pussila, a doctoral researcher at the University of Helsinki, Finland, will tell delegates at the annual conference of the European Society of Human Genetics, Barcelona, Spain, that there appears to be an association between the Western-style diet, which is rich in fat and low in fibre, vitamin D and folate, and the disease.
Using a mouse model, she and her team found that very early changes in normal colonic mucosa suggested a “colon-wide effect of events that predispose to cancer”, she said.
The team carried out a long-term diet experiment, using genetically engineered mice with Lynch syndrome and a mutation in MIh1, a mismatch repair gene. Lynch syndrome carriers have inherited one healthy and one mutated mismatch repair gene, and about an 80% risk of developing cancer.
Ms Pussila said: “We wanted to be able to spot cancer-predicting events in the colon mucosa before tumours developed. For this reason, we decided to use a mouse model which was already known to have a susceptibility to colon cancer.
“Interestingly, our 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. 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% of cancers were detected in WD fed mice.”
Typical Lynch syndrome tumour characteristics, such as lack of MIh1 protein or microsatellite instability, were not detected.
However, the researchers found that the MIh1 gene expression was already severely decreased in the mucosa, which suggests that a decrease in MIh1 gene expression may be enough to enable the development of tumours.
“It has been generally assumed that the development of cancer in Lynch syndrome carriers needs an inactivation of both the mismatch repair gene alleles, or pairs, involved, thus causing microsatellite instability,” Ms Pussila continued.
“However, our studies have shown that this is not necessarily the case, since a severely decreased amount of MIh1 without loss of the second allele and without microsatellite instability appears to be enough to provoke the development of tumours.
“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.”
Abstract no: C14 – Lynch syndrome mouse: A model for colon carcinogenesis
Leave a Reply