Part I – Where does pancreas cancer (adenocarcinoma) come from?

Most of the time, we do not know why an individual develops pancreas cancers. Medically, this is referred to as ‘sporadic’ (unknown cause). To our best knowledge, a poor diet does not cause pancreas cancer, a lack of exercise does not cause pancreas cancer, and we have not identified a single environmental agent or occupational agent that causes pancreas cancer. In this post, we will discuss an overview of 1) how pancreas cancer cells develop from normal pancreas cells, 2) some known inherited genetic conditions, and 3) precancerous cysts.

Pancreas cancer development

There are several kinds of pancreatic cancers. The most common type is a pancreatic adenocarcinoma. These adenocarcinomas develop when the normal cells of the pancreas duct get mutations that make them cancerous. All cells eventually reach the end of their life span and must replicate to create new cells. During this replication process, errors can happen leading to mutations. These errors and mutations can stack up. Sometimes, enough mutations align just perfectly enough that the damaged offspring cells become cancerous. A cancerous cell is one that grows uncontrollably causing destruction to surrounding cells. This process typically requires multiple damages/mutations to occur for a normal cell to go from damaged to cancerous. This process happens more often in older people as the cells have undergone more wear and tear with time and thus are prone to more errors. It also may happen in situations that cause more cell damage and turnover, such as pancreatitis (inflammation of the pancreas).

Inherited genetic conditions

Although most pancreas cancers are sporadic, there are a small number of pancreas cancers that are related to inherited genes. There is no single ‘pancreas cancer gene’, however certain genes that increase the risk of pancreas cancer above normal risk. For those with one of those genes, early screening is recommended. (On a related note – everyone diagnosed with pancreatic cancer should also undergo genetic screening to look for these inheritable genetic mutations)

As shown below, based on the gene mutation, the risk of pancreas cancer varies and so does the recommendation for screening. Screening for pancreas cancer is usually done with the use of an MRI, and sometimes with an endoscopic ultrasound. MRIs provide great images of the pancreas making it a useful test to pick up early pancreas cancers. It’s important to remember that even in the setting of a high-risk genetic condition, the risk of pancreatic cancer is only nominally greater than average risk.

Most major centers will have a pancreas screening program if you have one of these high-risk mutations. Your primary care doctor should be able to tie you into a pancreas screening program or connect you to an oncologist who would have access to the guidelines that guide screening. Below is an example of a reasonable screening strategy.

GenePreconditionScreening StrategyAge of OnsetFrequency
At least >1 first or second-degree relatives with pancreatic cancerMRI/MRCPAge 50 (or 10 years prior to earliest age of onset in the family)Annual
STK11NoneInitial EUS & MRI/MRCP Annual MRI/MRCPAge 30-35 (or 10 years prior to earliest age of onset in the family)Annual
CDKN2ANoneInitial EUS & MRI/MRCP Annual MRI/MRCPAge 40 (or 10 years prior to earliest age of onset in the family)Annual
NoneInitial EUS & MRI/MRCP Annual MRI/MRCPAt onset of pancreatitis, or beginning at age 40Annual

Cysts of the pancreas

Cysts are liquid filled growths on the pancreas. While most cysts are either benign (non-cancerous), or unlikely to ever develop into a cancer, there are some that are precancerous. These concerning cysts ought to be removed or watched closely.

Symptoms, blood work, MRIs and endoscopic ultrasound results can help identify the type of cyst and provide information regarding the risk of that cyst progressing into a cancer. There are very well-developed international guidelines that can guide a physician in figuring out how to manage these cysts. The factors that go into the guidelines include size, the way it looks on MRI, can sometimes analysis of the cyst fluid after a biopsy. If these cysts are found, check with a pancreatic surgeon or a gastroenterologist for follow-up and management.

Concluding thoughts

For most pancreas cancers, a specific cause cannot be identified. As a result, there are few actions that can be taken to prevent the development of pancreas cancer. Related to that is the fact that there isn’t much that a person does that leads to the development of pancreas cancer.

Exceptions are certain genetic mutations and pancreatic cysts. If you have one of these conditions, early screening can help identify a potential pancreas cancer in the pre-cancerous stage or at a very early stage. Reach out to your doctors to learn about whether you qualify for screening.

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