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We don’t know what causes pancreatic cancer. But we do know many of the risk factors for this cancer (see Pancreatic Cancer Risk Factors) and how some of them cause cells to become cancerous.

Gene changes that may lead to pancreatic cancer

Genes contain the instructions for making for proteins, which have many different functions within our bodies. Genes are made up of DNA. Alteration (mutations) in certain genes can lead normal cells to become cancerous. These genes control when 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 or cause cells to die at the right time are called tumor suppressor genes.

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

Inherited gene mutations

Some people inherit gene changes from their parents that raise their risk of pancreatic cancer. Sometimes these gene changes are part of syndromes that include increased risks of other health problems as well. These syndromes, which cause a small portion of all pancreatic cancers, are discussed in Risk Factors for Pancreatic Cancer.

Acquired gene mutations

Most gene mutations related to cancers of the pancreas occur after a person is born, rather than having been inherited. 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. Many gene changes are probably just random events that sometimes happen inside a cell, without having an outside cause.

Some of the DNA changes often seen in sporadic (non-inherited) cases of pancreatic cancer are the same as those seen in inherited cases, while others are different. For example, many sporadic cases of pancreatic cancer have changes in the p16 and TP53 genes, which can also be seen in some genetic syndromes. But many pancreatic cancers also have changes in genes such as KRAS, BRAF, and DPC4 (SMAD4), which are not part of inherited syndromes. Other gene changes can be found in pancreatic cancers, although often it’s not clear what has caused these changes.