Researchers find cause of rare gastric disease

An international study – led by QIMR Berghofer Medical Research Institute – has discovered the genetic cause of a rare gastric condition that can lead to stomach cancer.

The international study was led by Professor Georgia Chenevix-Trench, the head of the Genetics and Computational Biology Department at QIMR Berghofer, and included researchers from the University of Adelaide; the Genetic Services of Western Australia; the University of British Columbia, Canada; the University of Porto; and several institutions in the United States. It has been published in The American Journal of Human Genetics.

Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is an extremely rare condition in which the upper part of the stomach becomes carpeted with hundreds or thousands of benign growths, known as polyps. In some patients, the polyps can become cancerous over time. Some patients with GAPPS therefore opt to have their stomachs removed as a precaution.

After eight years of investigation, Professor Chenevix-Trench and her colleagues have discovered three extremely rare genetic mutations that cause the condition.

“We studied six different extended families around the world that all have members who suffer from this condition,” Professor Chenevix-Trench said.

“After much investigation, we found that members of each family carry one of these three extremely rare genetic mutations. These mutations sit right on top of each other near a gene known as APC and they all appear to do the same thing.”

The discovery means that in future individuals who have a family member with GAPPS will be able to have a DNA test to determine whether they will develop the condition.

“Those who do carry the mutation can be closely screened and can decide whether they want to consider surgery, and those who do not carry the mutation will no longer have to have regular screening,” Professor Chenevix-Trench said.

Professor Chenevix-Trench and her colleagues first began studying the genetic causes of GAPPS nearly 10 years ago after learning about a large, Australian extended family in which more than 30 people suffered from the condition.

“Because this was such a large family with so many members affected, we knew that this condition must have a genetic cause,” Professor Chenevix-Trench said.

“We fairly quickly found out which chromosome was involved. We thought it would be straightforward to then find the genetic mutation involved, but that ended up being much more difficult than we expected.

“We used the latest technology as it became available, but eventually we found the mutations using an old-fashioned technology.

“The reason the new technology didn’t find these mutations is because, unlike most mutations, these ones don’t work by changing a protein. Instead, we think they work by regulating the amount of protein that’s made.

“We don’t yet know how that process causes the polyps to form in the upper stomach.”