How Genetics Plays a Role
in Pancreatic Cancer

A Guide For Patients

Table of Contents


Pancreatic cancer has traditionally been very difficult to detect in early stages. Recent discoveries have uncovered new insights to help predict whether an individual may be at a higher risk for pancreatic cancer and should be routinely screened for early detection. 

Pancreatic cancer is one of the deadliest cancers in the United States with an average 5-year survival rate below 11% [1]. Why is this? Well, there are 2 main reasons. Because of the location of the pancreas in the body, pancreatic cancer can be difficult to detect in its early stages. Additionally, pancreatic cancer symptoms tend to be vague and similar to other gastrointestinal issues. Therefore, a healthcare provider may perform several diagnostic tests for other conditions before evaluating for pancreatic cancer.

Experts agree that knowing what risk factors can increase a person’s chances of developing pancreatic cancer and getting tested for certain risk factors (if appropriate), is currently the best way to reduce pancreatic cancer risk until more effective preventative strategies are developed [2]. 

In this guide, we’ll take a look at the basics of pancreatic cancer, what are some of the established risk factors, and if you should be evaluated for certain risk factors.

The Pancreas

The pancreas is an organ located behind the stomach and it provides two critical functions for your body:

  1. It makes and releases digestive enzymes to break down food in your digestive tract.
  2. It regulates your blood sugar by releasing insulin and other hormones.

Pancreatic cancer starts when cells in the pancreas grow out of control and form a tumor.

Types, Symptoms, & Causes of Pancreatic Cancer

Types of Pancreatic Cancer

There are 2 main types of pancreatic cancer.

1. Exocrine Pancreatic Cancers

Exocrine pancreatic cancers make up more than 95% of all pancreatic cancer diagnoses [3]. Exocrine pancreatic cancer begins when abnormal changes occur in the exocrine cells of the pancreas. The two major cell types of the exocrine pancreas are duct cells and acinar cells. Duct cells form the lining of the ducts of the pancreas. Acinar cells release digestive enzymes to help break down your food into digestible forms of sugars, proteins and fats. 



The following are types of exocrine pancreatic cancer:


More than 90% of pancreatic cancer diagnoses are adenocarcinoma [4]. The majority of adenocarcinomas begin in the lining of the ducts of the pancreas. This type of cancer is commonly referred to as pancreatic ductal adenocarcinoma (PDAC). Less frequently, it can develop in cells that make pancreatic enzymes. When the cancer forms in the acinar cells, it is known as acinar cell carcinoma.

Adenosquamous Carcinoma

About 1-4% of exocrine pancreatic cancers are adenosquamous carcinoma [4]. Although rare, it is a very aggressive cancer and tends to have less favorable outcomes than other exocrine pancreatic cancers.

Colloid Carcinoma

Colloid carcinoma accounts for about 1-3% of exocrine pancreatic cancers [4]. This cancer typically starts from a cyst, also known as an intraductal papillary mucinous neoplasm (IPMN). Colloid carcinoma is easier to treat than other pancreatic cancers because it is slow to metastasize.

Squamous Cell Carcinoma

This form of cancer is extremely rare and not well understood with respect to its cause, risk factors, biologic behavior, and response to treatments [5]. Squamous cell carcinoma has been reported to be aggressive and metastasizes quickly.

2. Pancreatic Neuroendocrine Tumors (NET)

Pancreatic Neuroendocrine Tumors (NETs) account for less than 5% of pancreatic cancers [6]. This type of cancer develops in the endocrine or islet cells of the pancreas. These cells are responsible for producing insulin and other hormones that help regulate blood sugar. Pancreatic NETs can be cancerous or not cancerous, but they can cause serious health problems either way.

Gastrinoma is known as a tumor that forms in gastrin (a hormone that helps to digest food)-producing cells.


Glucagoma is known as a tumor that forms in glucagon (a hormone that helps breakdown glycogen to glucose in the liver)- producing cells.


Insulinoma is known as a tumor that forms in insulin-producing cells. 

Other Islet Cell Tumors

These types of cancers affect cells that produce hormones to help the body regulate sugars, water, and salt.

Symptoms of Pancreatic Cancer

  • Nausea
  • Jaundice
  • Diarrhea
  • Indigestion
  • Loss of appetite
  • Pain in abdomen/ back
  • Unexplained weight loss
  • Fatigue
  • Gallstones
  • Vomiting
  • Abdominal bloating or swelling
  • Diabetes

Causes of Pancreatic Cancer

Pancreatic cancer is caused by changes in DNA.

These changes can be inherited, exacerbated by environmental stressors like smoking or drinking, or acquired by chance over the course of an individual’s life. The general population lifetime risk for developing pancreatic cancer is approximately 1.7% [1]. However, there are a number of factors that can increase or decrease your overall risk for developing pancreatic cancer.

Risk Factors

A number of risk factors have been associated with an increased occurrence of pancreatic cancer. These risk factors include:

  • Inherited genetic variant(s)
  • Family history
  • Smoking
  • Alcohol
  • Obesity
  • Age: 60 years and older
  • Diabetes
  • Pancreatitis
  • African American and Ashkenazi Jewish ancestry
  • Diet
  • Males have a slightly higher prevalence


Note: having one or more of these risk factors does not guarantee you will get pancreatic cancer. Most individuals with these risk factors do not develop pancreatic cancer.

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Pancreatitis & Pancreatic Cancer

What is your risk of developing pancreatic cancer if you have pancreatitis?

As described above, your pancreas makes enzymes to aid in digesting your food. In order to protect your pancreas from these enzymes, they are created and released in an inactive, harmless form. They travel from the pancreas to the small intestine, where they are activated and digest your meals.

Pancreatitis can develop when those pancreatic enzymes become active while still in the pancreas. Rather than breaking down food, these enzymes break down or digest the pancreas, leading to inflammation and organ damage.

Pancreatitis can be caused by a number of things including genetics, surgery, cystic fibrosis, heavy alcohol consumption, medications, and gallstones. 

It is clinically classified as acute or chronic.

Acute Pancreatitis

Acute pancreatitis occurs suddenly. Patients with acute pancreatitis typically present with severe abdominal pain and usually require emergency medical treatment. Some people who have had one attack of acute pancreatitis can go on to have several more attacks. Recurrent attacks of acute pancreatitis can lead to chronic pancreatitis. 

Patients with pancreatitis have an increased risk for developing pancreatic cancer after their first acute pancreatitis episode. 

The associated risk remains highest < 2 years from the initial episode and gradually decreases over time. A Danish study published in Gastroenterology in 2018, found that “within the first 2 years after admission for acute pancreatitis, the risk for these patients compared with the general population was increased 20-fold. From 2 to 5 years after the initial acute episode, the risk of pancreatic cancer was more than twice as high, and beyond 5 years, the risk remained double that of the general population” [7]. 

The association between acute pancreatitis and pancreatitis cancer may be due to acute pancreatitis being a presenting sign of the pancreatic cancer, rather than an isolated episode of acute pancreatitis rapidly leading to the development of pancreatitis. This association is most commonly seen in older patients.

Chronic Pancreatitis

Chronic pancreatitis is a long-lasting condition where the health of the pancreas worsens over time. Patients with chronic pancreatitis may have chronic pain, trouble digesting their food, and can develop diabetes. It is diagnosed by specific changes to the pancreas on imaging studies. Acute, chronic, and hereditary pancreatitis can increase a patient’s risk for developing pancreatic cancer.

According to a study published in Clinical Gastroenterology and Hepatology by Ariel Precision Medicine’s Co-Founder and Chief Scientific Officer, Dr. David Whitcomb, the prolonged inflammation and damage to the pancreas caused by chronic pancreatitis can increase one’s risk for pancreatic cancer. Based on his review, chronic pancreatitis can accelerate pancreatic cell injury and DNA damage, which may increase the risk for pancreatic cancer. Most individuals with chronic pancreatitis will not develop pancreatic cancer. The risk has been estimated to be ~5% over 20 years from the onset of most forms of chronic pancreatitis [8].

Hereditary Pancreatitis

Hereditary pancreatitis is a genetic condition that typically begins in late adolescence causing recurrent acute pancreatitis episodes that may eventually progress to chronic pancreatitis. Original studies suggested that patients with hereditary pancreatitis have up to a 40% lifetime risk for pancreatic cancer [9]. However, a more recent study indicates that the risk may be as low as 7.2% by age 70 years [10]. This lower estimate may reflect successful counseling of families with hereditary pancreatitis to avoid tobacco. As described by the National Pancreas Foundation, “this increased risk is heavily dependent upon the duration of chronic pancreatitis and environmental exposures to alcohol and smoking” [11].

For More Information on Pancreatitis

Genetic Risk for Pancreatic Cancer

Can pancreatic cancer be inherited?

About 10% of all pancreatic cancer cases are hereditary [12].

A hereditary disease is caused by harmful genetic variants (mutations). Genetic variants are passed down from a parent to offspring which increases their risk for developing the disease. Every person has two copies of a gene; one they inherit from their mother and the other from their father. Most individuals with a hereditary cancer predisposition syndrome inherit one normal copy of a gene from one parent and one abnormal copy from the other. As these individuals get older, the normal gene may get damaged due to environmental exposures like smoking or drinking. Eventually, some of these individuals may have two copies of a damaged gene in certain organs or tissues, which can cause a cell to grow abnormally and form a cancerous tumor.

Certain genetic variants can increase your risk for developing several different cancers. For example, variants in BRCA1 and BRCA2 genes are associated with hereditary breast, ovarian, pancreatic, melanoma and prostate cancers [13]. Additionally, several pancreatic diseases that can be hereditary, such as some forms of pancreatitis and diabetes, can increase your risk for pancreatic cancer. 


Knowing your family’s health history is very important when considering your own cancer risk.

The National Comprehensive Cancer Network (NCCN) recommends genetic testing for a hereditary cancer predisposition if you have a first-degree blood relative with exocrine pancreatic cancer [14]. Additional indications include a personal or close family history of multiple cancers, early-onset cancer, multiple closely related individuals with cancer, specific uncommon cancers (e.g., male breast cancer), or an identified pathogenic (harmful) genetic variant in a family member.

The NCCN also recommends genetic testing if you have or have had pancreatic cancer even if you have no family history of it. A breakthrough study published in the Journal of American Medical Association (JAMA) suggests that genetic variants are more prevalent in patients with pancreatic cancer who may have no known family history, than previously thought [15]. A genetic counselor can help you determine if you are eligible for genetic testing, identify the type of genetic testing that is appropriate for you, discuss the benefits and limitations of genetic testing, and guide you through the genetic testing process should you choose to move forward.

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Detection & Screening 

How can pancreatic cancer be diagnosed early?

Pancreatic cancer is difficult to diagnose in early stages because it typically has vague symptoms that are often overlooked or attributed to another condition. The majority of pancreatic cancer diagnoses are diagnosed at stage 4 and have about a 1% five-year survival rate [8].  Although there is no standard diagnostic tools available to screen for pancreatic cancer in the general public, there are screening and detection programs, called surveillance programs, available for individuals who meet eligibility criteria for being at a high risk.
The earlier pancreatic cancer is diagnosed the better the overall prognosis will be. Cancer that is detected early has more treatment and surgical options. This is why it is incredibly important to determine if you are at a higher risk so that your healthcare team can implement appropriate early survalience strategies into your care plan.

Early detection and screening strategies include:

  • Genetic counseling and testing
  • Imaging tests
  • Computed tomography (CT) scan
  • Magnetic resonance imaging (MRI)
  • Ultrasound
  • Cholangiopancreatography
  • Positron emission tomography (PET) scan
  • Angiography
  • Blood tests
  • Biopsy

Genetic Testing

There are two types of genetic testing available for pancreatic cancer. Both types of testing are typically ordered by a licensed healthcare professional.

Germline Testing

Germline testing evaluates your genetic risk for pancreatic adenocarcinoma (the most common form of pancreatic cancer) before or after a diagnosis. This type of testing assesses genetic variants (mutations) you may have inherited that increase your lifetime risk for developing pancreatic, breast, colon, prostate, and melanoma. Germline testing is done using a blood or saliva sample. 

There are several germline tests for pancreatic cancer available but many of them are lacking in relevancy and actionability. Many evaluate an array of genes that have little or undefined evidence to support their risk for pancreatic and other cancers.  These findings may be uninformative and can have a higher likelihood of identifying a genetic variant of uncertain significance, which increases the risk of misinterpretation and patient mismanagement.  Additionally, these findings will have no accompanying clinical guidance to help direct your future care. 


ArielDx® Pancreatic Cancer

This is why it is important to choose a germline test, like ArielDx Pancreatic Cancer, that will provide accurate and actionable insights the first time.

ArielDx Pancreatic Cancer® evaluates 14 genes that have the most clinical evidence for cancer risk. When relevant, the report contains personalized clinical guidance to help you and your healthcare provider determine appropriate next-steps. Ariel’s clinical guidance is supported by the most current scientific evidence from the world’s leading pancreatologists so you and your healthcare provider will be equipped with the most up-to-date findings.

ArielDx Pancreatic Cancer uses a non-invasive and simple testing process. Once your healthcare provider has planned an order, you will receive an email invitation to complete registration for testing. Once you complete registration, Ariel will get in touch with you to review your insurance eligibility and benefits, so you will know upfront what the out-of-pocket costs may be and then you can decide whether you’d like to proceed with testing. Ariel will send you an easy-to-use DNA collection kit to your home where you will collect your saliva sample and send it back to Ariel’s lab for analysis. Your results will be released to your healthcare provider first so they can go over the findings with you. To further support you and your care, Ariel also offers genetic counseling services so you can meet one-on-one with a genetic counselor to answer any of your questions about the test and what it can mean for you and your family.

Somatic Testing

Somatic testing is done after a diagnosis of a tumor or cancer. This type of testing analyzes genetic variants within the cells of the tumor itself. Somatic testing provides insight to help confirm a diagnosis, the prognosis of the cancer, and specific treatments that may be available. Since somatic testing only evaluates cancer cells in a particular region of the body, it cannot be used to evaluate a genetic risk for developing cancer.

Eligibility for Pancreatic Cancer Surveillance Programs

How can you get checked for pancreatic cancer early?

Since pancreatic cancer is hard to detect and is often diagnosed late, it is important to know whether you may be eligible for early detection and screening programs, also known as surveillance programs.

You may be eligible if you have a:

  • Genetic variant that carries a higher risk for pancreatic cancer
  • Family history of pancreatic cancer
  • History of pancreatitis
  • Pancreatic cyst

Talk to your healthcare provider to determine your eligibility. 

pancreatitis patient talking to his provider about his care

Additional Resources

Pancreatic Cancer Discussion Guide

Get our pancreatic cancer discussion guide to have a more informed discussion about genetic testing with your healthcare provider.

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10. Shelton CA, Umapathy C, Stello K, Yadav D, Whitcomb DC. Hereditary Pancreatitis in the United States: Survival and Rates of Pancreatic Cancer. Am J Gastroenterol. 2018;113(9):1376. doi:10.1038/s41395-018-0194-5. PMID: 30018304.

11. Hereditary Pancreatitis. The National Pancreas Foundation.,exposures%20to%20alcohol%20and%20smoking. Accessed November 3, 2021.

12. Genetics and Hereditary Factors of Pancreatic Cancer. Pancreatic Cancer Action Network. Accessed November 3, 2021.

13. The Genetics of Cancer. National Cancer Institute. Updated October 12, 2017. Accessed November 3, 2021.

14. National Comprehensive Cancer Network. Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic. (Version 1.2022). Updated August 11, 2021. Accessed November 3, 2021.

15. Hu C, Hart SN, Polley EC, et al. Association Between Inherited Germline Mutations in Cancer Predisposition Genes and Risk of Pancreatic Cancer. JAMA. 2018;319(23):2401–2409. doi:10.1001/jama.2018.6228.