The hereditary condition, Lynch syndrome, makes people more likely to get certain cancers, so it is essential that the condition is diagnosed early. However, current genetic tests don’t pick up all cases of Lynch syndrome. Professor Robyn Ward and her team have discovered new causes of this condition, which could change screening practices around the world.
Lynch syndrome is a hereditary cancer condition that makes people more likely to develop bowel, uterine and other cancers. These tumours develop at a young age, often when a person is under 50. The syndrome is usually caused by the inheritance of sequence mutations, or spelling mistakes, within the code of a certain group of genes called MMR genes. However, about 30% of people with suspected Lynch syndrome do not have these sequence errors. Professor Ward set out to understand what causes Lynch syndrome in this group of people.
Professor Ward and her team have uncovered a number of people with Lynch syndrome who have a different kind of biological defect. This type of defect is not picked up by current genetic tests for Lynch syndrome.
The researchers found that for these people, the sequencing of their genes is completely normal and there are no spelling mistakes, instead, one of their MMR genes has actually been switched off. The effect is the same though, and this type of defect causes a similar increase in cancer risk.
The research team has screened a large number of people with suspected Lynch syndrome to identify those who have these sorts of defects. They have also discovered other genetic changes which may inactivate a person’s MMR genes and lead to Lynch syndrome.
To date, routine genetic testing has only looked at the parts of MMR genes known to be linked with Lynch syndrome. As a result, some people with Lynch syndrome go undetected and miss out on being able to take preventative action to manage their cancer risk.
By identifying several new genetic changes associated with Lynch syndrome, this project has opened up the door to new diagnostic opportunities. People suspected of having Lynch syndrome could undergo additional testing for switched off genes and other defects that explain the existence of cancer in their family. This will then guide clinicians and genetic specialists in how they assess a person’s cancer risk, and how often they screen the person to pick up disease early. Ultimately, these findings could drive changes to routine genetic screening practices around the world to include the early detection of these genetic abnormalities.
Professor Robyn Ward and Dr Megan Hitchins University of New South Wales