New genetic cancer risk uncovered

Updated: Aug 16, 2011, 12:58 PM IST

Melbourne: Scientists in Australia have claimed to have made a vital discovery about cancer being passed on in some families.

According to AAP report, the scientists have found that subtle changes to the outside of an anti-cancer gene attract a paralysing biochemical which stops the gene working,
significantly increasing a person`s risk of developing the life-threatening disease.

Until recently, it was known changes inside the cancer prevention gene MLH1 could be passed from one generation to the next and increase the risk of developing bowel, uterine
and other cancers by up to 80 per cent.

However, it was revealed that about why around 30 percent of families with a history of cancer did not show any changes inside their MLH1 genes.

The discovery about the crucial impact that external changes to MLH1 can have in passing on cancer was based on a study of a large family by scientists from University of New South Wales (UNSW) and University of Western Australia.

The West Australian family`s grandmother was diagnosed with uterine cancer and two types of bowel cancer, while two of her five children had colorectal cancer.

While genetic tests couldn`t find any common changes within their MLH1 genes to suggest why the disease was passed on, the scientists fond their MLH1 genes had instead undergone a tiny external chemical change which was passed on and increased the cancer risk across three generations.

The change involved a single letter in the DNA sequence at the start of the MLH1 gene, which essentially amounted to a "spelling mistake", the report said adding that mistake made the gene attract a biochemical tag known as methylation, which sat on top of the DNA and switched off the gene and its ability to prevent cancer.

"What we found was that a subtle change near the gene was acting like a magnet to attract methylation," study co-leader Dr Megan Hitchins, from UNSW`s Lowy Cancer Research Centre, said.

"So it was not the methylation itself that was being passed from parent to child but rather
the DNA change, and this acted as a methyl magnet.

"In families with a history of cancer due to changes in the MLH1 gene, all members are offered regular medical checks such as colonoscopies to detect early signs of the disease
because doctors don`t know who carries the genetic abnormality.

However, now that scientists know that external changes to the MLH1 gene can flag a cancer risk, only family members with the genetic change will need regular checks.

"It`s very important for us as clinicians to identify who is at risk and who isn`t," Dr Hitchins` colleague at the Lowy centre and co-author of the study Professor Robyn Ward said.

"Having done this study we can now discharge some family members from screening because we can pick up which ones have the change and which ones don`t, so not as many have to have invasive screening tests.

"The study was published in the international scientific journal Cancer Cell.

PTI