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Scientists don’t know exactly what causes most pancreatic neuroendocrine tumors (pNETs), but they have found several risk factors that can make a person more likely to get this disease. Some of these risk factors affect the DNA of cells in the neuroendocrine system in the pancreas, which can result in abnormal cell growth and may cause cancers to form.

DNA is the chemical in our cells that carries our genes, which control how our cells function. We look like our parents because they are the source of our DNA. But DNA affects more than just how we look.

Some genes control when our cells grow, divide into new cells, and die:

• Genes that help cells grow, divide, and stay alive are called oncogenes.
• Genes that help keep cell division under control, repair mistakes in DNA, or cause cells to die at the right time are called tumor suppressor genes.

Cancers can be caused by DNA changes (mutations) that turn on oncogenes or turn off tumor suppressor genes.

Inherited gene mutations and pancreatic neuroendocrine tumors (pNETs)

Although 90% of pNETs are sporadic (random), some people inherit gene changes from their parents that raise their risk of pancreatic NET. Sometimes these gene changes are part of syndromes that increase risks for other health problems, as well.

Syndromes related to changes in three tumor suppressor genes are responsible for many inherited cases of pNETs:

• Multiple Endocrine Neoplasia Type 1 (MEN1) syndrome: Most inherited cases of pNETs are due to changes in the MEN1 gene. This syndrome can cause cancer in the pancreas, parathyroid glands, and pituitary glands. These tumors usually happen at younger ages and tend to be non-functioning. Screening people with the MEN1 gene or their family members can sometimes help find pancreatic NET before symptoms appear.
• Von Hippel-Lindau (VHL) syndrome: Changes in the VHL gene cause a small number of pNETs, usually developing at earlier ages (sometimes as early as the 20s). These tumors tend to be non-functioning and slow growing.
• Neurofibromatosis type 1 (NF1) syndrome: A small number of pNETs (usually somatostatinomas) are caused by changes in the NF1 gene. Other cancers are also associated with this syndrome, including brain tumors or benign tumors that form in nerves under the skin (neurofibromas),

The treatment for a pNET caused by a genetic syndrome might be slightly different compared with treatment for a pNET in someone without a gene mutation.

Acquired gene mutations in pancreatic neuroendocrine tumors (pNETs)

Most gene mutations related to neuroendocrine tumors of the pancreas are random. If these random mutations occur after a person is born, they are called acquired. These acquired gene mutations sometimes result from exposure to cancer-causing chemicals (like those found in tobacco smoke). But often what causes these changes is not known.