While it is virtually impossible to tell what caused a specific person to develop pancreatic cancer, cancer biology principles and population-based studies can help us understand why pancreatic cancer develops.

What causes pancreatic cancer?

Pancreatic cancer is fundamentally a disease caused by damage (or "mutations") to the DNA. These DNA mutations can occur in one of three ways: they can be inherited, they can be caused by behaviors such as smoking, or they can occur by chance.

Inherited Mutations   

Gene mutation

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 we inherit from our father. Most individuals with an inherited cancer syndrome inherit one mutant copy (let us say from dad) and one 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.

Not everyone with an inherited predisposition will get cancer. Rather, 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.

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Our Behavior   

Smoking bona kim

Our behavior can damage our DNA. For example, if the carcinogens (cancer-causing chemicals) in cigarette smoke 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!

Caused By Chance   

Genetics

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.

If there is pancreas cancer in your family, we need your help.

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Risk Factors for Pancreatic Cancer

The major risk factors for pancreatic cancer include:

Cigarette smoking   

Cigarette smoking doubles the risk of pancreatic cancer, and the more cigarettes a person smokes during their life, the greater the risk. 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, after ten years, the risk of pancreatic cancer drops close to normal in people who quit smoking. Switching from non-filtered to filtered cigarettes does not appear to decrease risk. Simply put, cigarette smoking is the leading preventable cause of pancreatic cancer.

Age   

Age is one of the biggest risk factors for pancreatic cancer. The risk of developing pancreatic cancer increases with age. Over 80% of pancreatic cancers develop between the ages of 60 and 80 years. When pancreatic cancer occurs in younger people, it is sometimes because the person has a specific risk factor, such as having received radiation therapy during childhood.

Race   

Studies in the United States have shown that pancreatic cancer is more common in the Black population than it is in the White population. The reasons for this are not clear. Some of this increased risk may be due to socioeconomic factors, obesity and cigarette smoking. There have not been enough detailed genetic studies to determine if there is also an underlying genetic (inherited) explanation. Not only is pancreatic cancer more common in Blacks than it is in Whites, but studies have reported that Black patients do worse when they are diagnosed with pancreatic cancer. The reported survival of White patients is longer than the survival of Black patients, on average Black patients present at an earlier age than White patients, and Black patients tend to have more advanced disease at presentation.

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Gender   

Cancer of the pancreas is more common in men than in women. This difference is seen across races. White men are more likely to develop pancreatic cancer than are White women, and Black men are more likely to develop pancreatic cancer than are Black women. Some of this may be related to cigarette smoking, as historically men have been more likely to smoke than women.

Ashkenazic Jewish 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. These inherited BRCA2 mutations increase the risk of both breast and pancreatic cancer.

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Chronic Pancreatitis   

Long-term (chronic) inflammation of the pancreas (pancreatitis) has been linked to cancer of the pancreas. It is believed that repeated bouts on injury and repair, as is seen in chronic pancreatitis, together with the inflammatory mediators released during pancreatitis, conspire to increase the risk of cancer. Of note, pancreatitis is not only a risk factor for pancreatic cancer, but, but because cancers can block the pancreatic duct, pancreatic cancer can also cause pancreatitis.

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. The reasons behind these associations are not understood. Several investigators have suggested that older patients with new onset diabetes should be screened to see if they have a pancreatic cancer.

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. Although it hasn't been proven, it is hoped that weight loss will reduce risk in the obese population.

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.

Genetics   

A number of inherited cancer syndromes increase the risk of pancreatic cancer. These include the breast cancer syndrome (caused by inherited variants in the BRCA2, BRCA1 and PALB2 genes), familial atypical multiple mole melanoma syndrome (FAMMM, caused by inherited variants in the CDKN2A gene), Lynch syndrome (also known as hereditary non-polyposis colorectal cancer syndrome), and the Peutz-Jeghers syndrome (caused by inherited variants in the LKB1 gene).

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