A risk factor is anything that increases a person’s chance of developing a tumor. Although risk factors can influence the development of a tumor, most do not directly cause the disease. Some people with several risk factors never develop a tumor, while others with no known risk factors do.

The majority of GISTs develop for no known reason, called sporadic. There are no known environmental or behavioural risk factors contributing to GIST. Therefore, patients should not worry that their diet or lifestyle choices contributed to GIST.

Random genetic mutations are the apparent cause of GISTs. The majority of GISTs show identified mutations in cell-surface proteins called tyrosine kinase receptors. Most GISTs show mutations in a gene that produces a growth factor receptor called KIT.

However, there are rare examples of GIST running in families due to an inheritable germline mutation. In addition, people affected by neurofibromatosis type 1 (NF1) have an increased chance of developing GIST.