The Sol Goldman Pancreatic Cancer Research Center

What causes pancreatic cancer?

While it is virtually impossible to tell what caused a specific person to develop pancreatic cancer, there are some important principles of cancer biology that can help us understand why pancreatic cancer develops, and large population-based studies help us understand the many risk factors for this disease.

Pancreatic cancer is fundamentally a disease caused by damage to the DNA. This damage is often referred to as mutations. These mutations can be inherited from mom or dad, or they can be acquired as we age. First, let us look at the inherited mutations. Remember that we have two copies of each gene - one copy we inherit from our mother, the other copy we inherit from our father. Most individuals with an inherited cancer syndrome inherit one mutant copy (let us say from dad) and one intact (normal) copy (let us say from mom) of a cancer associated gene. As these individuals with an inherited cancer syndrome age, some of will sustain damage the good copy of the gene (the copy they got from mom) in a cell in their pancreas. That cell will then have two damaged copies of the gene (one inherited and one acquired during life), and, as a result, that cell in the pancreas will begin to grow abnormally and will eventually form a cancer.

From this understanding it should be clear that not everyone with an inherited predisposition will get cancer. Instead, since individuals with an inherited cancer syndrome are born with only one good copy of the cancer associated gene, they are more likely to get cancer. We like to think of it using the analogy of the space shuttle, with the shuttle representing a person, and computers on the space shuttle representing genes. Normally the shuttle goes into space with a computer and a back-up for that computer (we have two copies of each gene). Only if both computers break is there a problem. For people with a genetic predisposition to pancreatic cancer, it is like going up into space with one good computer and one bad computer. If something goes wrong with the one good computer, they are in trouble.

The second way we can damage our DNA is with our behavior. For example, the carcinogens (cancer causing chemicals) in cigarette smoke can damage our DNA. If the carcinogens damage a key cancer-associated gene in a cell in the pancreas, then that cell may grow into a cancer. Simply put, don’t smoke!

The third way our DNA gets damaged is by chance. This is probably the least satisfying explanation, but it is true. Every cell in our body (and there are trillions of them!) contains two copies of each of the 23 chromosomes and these 46 chromosomes contain billions of base-pairs (letters) of DNA. Every time a cell divides it has to copy all of that DNA (so that it can make daughter cells with a full complement of DNA). The DNA copying machinery in cells is pretty darn good, but it is not perfect. Occasionally mistakes are made copying DNA. On one hand, this is good from the perspective of a population or species, because these mistakes allow for evolution to occur (if we copied our DNA perfectly we would not evolve!). On the other hand, if one of these chance mistakes in copying (DNA mutations) damages a key cancer-associated gene in a cell in the pancreas, then that cell may grow into a cancer.

genetics

To summarize, pancreatic cancer is caused by DNA mutations, and there are three ways that we can damage our DNA. We can be born with a DNA mutation inherited from our mother or father, we can do something, like smoking, that damages our DNA, or finally our DNA can be damaged by chance.

The second way to answer the question about what causes pancreatic cancer is to ask what are the risk factors for pancreatic cancer? Some of the risk factors include:

  1. Cigarette smoking:illustration of person smokingCigarette smoking doubles the risk of pancreatic cancer. In fact, some scientists have estimated that one in four, or one in five cases of pancreatic cancer are caused by smoking cigarettes. Smoking is also associated with early age at diagnosis. Very importantly, the risk of pancreatic cancer drops close to normal in people who quit smoking. Simply put, cigarette smoking is the leading preventable cause of pancreatic cancer.
  2. Age: The risk of developing pancreatic cancer increases with age. Over 80% of pancreatic cancers develop between the ages of 60 and 80 years.
  3. Race: Studies in the United States have shown that pancreatic cancer is more common in the African American population than it is in the white population. Some of this increased risk may be due to socioeconomic factors and to cigarette smoking.
  4. Gender: Cancer of the pancreas is more common in men than in women. Men are more likely to smoke than women.
  5. Religious background: Pancreatic cancer is proportionally more common in Ashkenazi Jews than the rest of the population. This may be because of a particular inherited mutation in the breast cancer gene (BRCA2) which runs in some Ashkenazi Jewish families.
  6. Chronic pancreatitis: Long-term (chronic) inflammation of the pancreas (pancreatitis) has been linked to cancer of the pancreas.
  7. Diabetes mellitus: Diabetes mellitus (sugar diabetes) can be a symptom of pancreatic cancer, and long-standing adult-onset diabetes also increases the risk of pancreatic cancer.
  8. Obesity: Obesity significantly increases the risk of pancreatic cancer. Believe it or not, it has been estimated that 8% of cancers are related to obesity.
  9. Diet: Diets high in meats, cholesterol, fried foods and nitrosamines may increase risk, while diets high in fruits and vegetables reduce risk. The vitamin folate may be protective.
  10. Genetics: As mentioned earlier, a number of inherited cancer syndromes increase the risk of pancreatic cancer. These include the breast cancer syndrome (BRCA2 and PALB2), familial atypical multiple mole melanoma syndrome (FAMMM), Lynch syndrome (also known as hereditary non-polyposis colorectal cancer syndrome), and the Peutz-Jeghers syndrome. More information about these syndromes is provided in the genetics section of this web page and on the web site of the National Familial Pancreas Tumor Registry.