Ms Fabienne Grieu loading samples into
the instrument used for genotyping in the
study.
Image: University of Western Australia

Researchers from the University of Western Australia have identified a genetic variation in the MTHFR gene that increases the risk of developing tumours on one side of the large bowel.

Importantly, the research also identified increasing dietary consumption of folate reduces the risk of developing these tumours.

Previous research findings by Professor Barry Iacopetta from the School of Surgery at the University of WA showed that tumours that arose on one side of the large bowel responded differently in therapy to tumours that arose on the other side.

In light of this finding, Professor Iacopetta with Associate Professor Lin Fritschi from the Western Australian Institute for Medical Research, hypothesised that cancers that developed on one side of the large bowel might have different risk factors from the other side because they followed different molecular pathways.

To test the genetic risk factors, Professor Iacopetta and his research group examined polymorphisms (genetic variations) in the methylenetetrahydrofolate reductase (MTHFR) gene that is known to be involved in the methylator phenotype – a major molecular pathway implicated in bowel cancer.

“The hypothesis was that tumours from the left and right side of the large bowel would have different dietary and genetic risk factors,” says Professor Iacopetta.

“We also had to look at these risk factors in relation to dietary intake of folate because folate is a carrier of methyl groups and it was the methylation pathway we were looking at.

“We found that a polymorphism in the MTHFR gene was a risk factor for tumours on one side of the large bowel but not the other, particularly for older people and people with low folate intake.

“But once these people increased their folate intake, the risk disappeared, it would go back to normal levels.”

According to Professor Iacopetta, a diet consisting of folate-rich foods such as fresh green vegetables could help to reduce the risk of bowel cancer.

Professor Iacopetta and his research group also identified another polymorphism in the delta DNMT3b gene, which was found to be a risk factor for tumours on one side of the large bowel.

“Again we showed that it was a risk factor for tumours on one side of the large bowel but not the other,” he says.

“When you’re looking at genetic factors of risk you have to be very careful to delineate where the tumours arise in the large bowel because there’s more than one pathway.

“That also holds for various tumour types, for example, breast cancer or gastric cancer.”
 
The research was funded by the National Health and Medical Research Council of Australia, and was published in the International Journal of Cancer, July 1 2009.