Study develops clearer picture for bowel cancer risk

Dec 23 2013

Professor Rodney Scott

Patients with a high hereditary risk of developing colorectal cancer will benefit from a new international study involving Hunter Medical Research Institute geneticist Professor Rodney Scott which refines the global database of genetic information.

The research, published today in the prestigious international journal Nature Genetics, focused on genetic faults responsible for Lynch Syndrome, an inherited condition affecting around five per cent of the 15,000 people diagnosed with colorectal cancer in Australia each year.

Doctors will now be able to give patients a more accurate picture of their familial risk and, if necessary, offer early screening.

“We were one of the main contributors to the study because we have the largest collection of hereditary colorectal cancer cases of any single institute in the country, if not the world,” Professor Scott, co-leader of HMRI’s Information Based Medicine Program, said. “The study was locus-specific to a particular disorder with a restricted number of genes, and we were looking for variants in those genes.

“With genetic screening you get three options – either positive results that are obviously pathogenic, clear results, or you get variants of unknown significance. With those variants we did additional studies and compiled a list of around 200 gene changes and we also helped classify some of the remainders.”

Patients previously tested for Lynch Syndrome were sometimes told they had variants of unknown significance, leaving them unsure whether they or family members faced the higher risk. Professor Scott said the study was the first to systematically characterise the variants and reduce the uncertainty.

“We can now characterise many of the variants as either pathogenic or non-pathogenic, which means we can define who should get additional screening procedures, or alternatively we can reassure people they don’t have additional risk.”

The risk factor ranges from 20- to 80 per cent for those carrying an inherited mutation in one of the four genes associated with colorectal cancer. These people need to be monitored considerably earlier than those commonly screened once turning 50, Professor Scott added.

He advises those with a familial history to see their GP and obtain a referral to a family cancer clinic.

The research team was coordinated by Professor Maurizio Genuardi from the University of Florence along with Professor Finlay Macrae from Royal Melbourne Hospital. The International Society for Gastrointestinal Tumours (InSiGHT) committee compiled data from around the world.

The findings in Nature Genetics can be viewed at

HMRI is a partnership between the University of Newcastle, Hunter New England Health and the community.