Risk Factors

A risk factor is anything that increases a person’s chance of developing cancer. Some risk factors can be controlled, such as smoking, and some cannot be controlled, such as age and family history. Although risk factors can influence the development of cancer, most do not directly cause cancer. Some people with several risk factors never develop cancer, while others with no known risk factors do. However, knowing your risk factors and communicating them to your doctor may help you make more informed lifestyle and health-care choices.

The only known risk factor for GIST is family history of the disease, when there is a small increase in risk of developing GIST. GIST is frequently associated with mutations in the KIT gene, and less commonly with mutations in a related gene called PDGFRA. The majority of these mutations are found only in the tumor tissue itself and cannot be inherited through a family. However, some families with inherited mutations in the KIT gene have been identified. In addition to multiple occurrences of both benign and malignant GIST, many of these families are also found to have increased skin pigmentation (coloring) under the arms, on the hands and face, and on the perineal skin (the area between the rectum and the genitals). There have also been families described with heritable mutations in the KIT gene that have only GIST and no unusual pigmentation. In all families with KIT mutations, GIST develops in adulthood. It is likely that there are other genes that have not yet been identified that play a role in the development of GIST.

In addition, a new inherited syndrome characterized by multiple gastric (stomach) stromal tumors and multiple paragangliomas (tumors on the nerves; primarily in the neck, chest, and abdominal wall) has been proposed, and research is ongoing. The gene associated with this condition has not yet been identified.

Approximately 7% of people with the hereditary syndrome neurofibromatosis type 1 (NF1) have GIST. The most common features of NF1 are multiple neurofibromas (tumors starting in nerves that cause lumps. These lumps often cause nodules on the skin of affected people), freckling under the arms and in the groin area, multiple café-au-lait spots (areas of light brown pigmentation) on the skin, and a symptom affecting the iris of the eye, called Lisch nodules. The gene associated with NF1 is also called NF1.

The KIT gene mutations, the newly described syndrome of GISTs and paragangliomas, and NF1 all follow an autosomal dominant inheritance pattern, in which a mutation happens in only one copy of the gene. This means that a parent with a mutation may pass on a copy of their working gene or a copy of their altered gene. Therefore, a child who has a parent with a mutation has a 50% chance of inheriting that mutation.

Because no other controllable risk factors have been identified, there is no way to prevent GIST.