New Hereditary Mutation Identified to Increase Pancreatic Cancer Risk

While studying a cancer-prone family, scientists have identified an inherited gene mutation that considerably enhances the risk of pancreatic and other cancers. The previously unknown mutation was defined in Nature Genetics by researchers at Dana-Farber/Brigham and Women’s Cancer Center. The discovery could lead to the routine testing of those with a family history of pancreatic cancers to uncover the mutation known as RABL3. If the mutation is identified, pancreatic cancers may be diagnosed earlier and in a stage that is much more treatable.

Because about 10% of pancreatic cancers reveal some type of genetic pattern, relatives of those carrying the variation may also choose to be tested. Other mutations have been identified in the past, but in most cases the cause of these cancers is unknown.

The recently identified RABL3 mutation dramatically increases the likelihood that cancer will develop at some point in a person’s life. Treatment options for pancreatic cancers are limited and the discovery of these anomalies may give the insight to establish new preventive measures as well as avenues to treat active cancers.

The discovery was made while investigating a family in which five members suffered from pancreatic cancer and multiple members had been diagnosed with other cancers. The pattern suggested a genetic mutation was being passed through the family. Not only was the mutation identified in several family members who had been previously diagnosed with cancer, but also in one who has not been diagnosed with any form.

Researchers then moved their focus to zebrafish. The genetic mutation was then recapitulated in large populations of zebrafish so that studies could be performed more rapidly to assess the impact on cancer risk. The zebrafish with the RABL3 mutation had much higher rates of cancer.

The RABL3 is a susceptibility gene mutation that individuals are born with, unlike somatic mutations that occur during a lifetime and can cause cells to become malignant. The mutation accelerates the movement of the KRAS protein within the affected cell. This increased movement helps the protein to take hold and trigger events that support the growth of cancer.

While the mutation is rare in the general population, testing for it in other families could reveal the cause for patterns of predisposition. The identification of the mutation in families would shine more light on which members should consider screenings. Testing for this mutation is expected to be recommended in the future for any person with a strong family history of pancreatic cancer.