What Causes Pancreatic Cancer?

QuestionsWe are often asked about the causes of 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 (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 mom, the other copy we inherit from dad.  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 they age, some of these people will damage the good copy of the gene (the copy they got from mom) in a cell in their pancreas.  That cell will have two bad copies of the gene, and, as a result, that cell in the pancreas will grow into a cancer.  It doesn’t mean that everyone with an inherited predisposition will get cancer, it means that since they only have one copy of the gene, they are more likely to get cancer.  I like to think of it using the analogy of the space shuttle, with the shuttle standing in for a person, and computers on the space shuttle standing in for genes.  Normally the shuttle goes into space with a computer and a back-up for that computer.  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.  The carcinogens 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 a 23 chromosomes and these 23 chromosomes contain 3 billion base-pairs of DNA.  Every time a cell divides it has to copy all of that DNA (so that it can make a daughter cell 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.  On one hand, this is good from a population or species perspective, because these mistakes allow for evolution to occur (if we copied our DNA perfectly we would not evolve!).  If one of these chance errors in copying (DNA mutations)  damage a key cancer-associated gene in a cell in the pancreas, then that cell may grow into a cancer.

Pancreatic Cancer and DNA

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 mom or dad, we can do something, like smoke, that damages our DNA, or 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: Smoking doubles the risk of pancreatic cancer. Smoking is also associated with early age at diagnosis, and, 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.  In fact, some scientists have estimated that one in four, or one in five cases of pancreatic cancer are caused by smoking cigarettes.
  2. Age: The risk of developing pancreatic cancer increases with age. Over 80% of the cases develop between the ages of 60 and 80.
  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 inflammation of the pancreas (pancreatitis) has been linked to cancer of the pancreas.
  7. Diabetes: Diabetes is both 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.
  9. Diet: Diets high in meats, cholesterol fried foods and nitrosamines may increase risk, while diets high in fruits and vegetables reduce risk. Folate may be protective.
  10. Genetics:  As mentioned earlier, a  number of inherited cancer syndromes increase the risk of pancreatic cancer.  These include inherited mutations in the BRCA2, FAMMM, or Peutz-Jeghers genes.  To learn more about familial pancreatic cancer visit the web site of the National Familial Pancreas Tumor Registry (http://pathology.jhu.edu/pancreas/NFPTR/).

Dr. Ralph H. Hruban

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34 Responses to “What Causes Pancreatic Cancer?”

  1. Susie Says:

    Thanks for this write-up, Dr. Hruban. That was very helpful to read! We struggle with trying to understand why these things happen to our loved ones and I feel like I have a better grasp of the situation now.

  2. Jeanine Says:

    I’ve done a lot of research on pancreatic cancer since my husband was diagnosed with it in March 2006. This is the best and most concise explanation I’ve ever read. Thank you for doing such a good explanation.

  3. Dr. Ralph Hruban Says:

    It sounds like your husband has a strong family history of cancer. I would suggest that he see a trained cancer genetics counselor for clinical discussion of his cancer genetics. He may also wish to join the National Familial Pancreas Tumor Registry at John Hopkins. Emily Palmisano, the coordinator of the NFPTR (http://pathology.jhu.edu/pancreas/NFPTR/) can provide you with more details on how to join the registry. My sincere best wishes to you, your husband and his family.
    Dr. Hruban

  4. Dr. Ralph Hruban Says:

    John: Good question. The link is strongest for cigarette smoking. Some studies have linked passive smoking with pancreatic cancer (growing up in a house in which someone else smoked), but the association there, as you might expect is weaker. The evidence for pipe or cigar smoking is even weaker. Dr. Hruban

  5. john Says:

    thanks, dr. hruban. i think it’s awesome that you guys have a blog and that you even personally respond to everyone. i hope you continue to post regularly.

    also, my mom is being treated for pancreatic cancer at johns hopkins. she’ll be back in a few months, so keep an eye out for her.

  6. Chris Amato Says:

    Dr. Rhuban

    Have you ever seen a patient with long-term (10 years +) chronic pancreatitis who subsequently exhibits irregular cells in the pancreas that are not cancerous – but look a lot like cancer? (and are diagnosed as cancerous)


  7. Helen Says:

    I have a family history of pancreatic cancer….two aunts and one cousin…all three succumbed to this cancer.

    I saw the TV special about Randy Pausch, the professor at Carnegie Mellon who died in July 2008 of pancreatic cancer. He cited one of his symptoms–stools that float in the toilet.

    My stools have floated for as long as I can remember. Is this a concern? Thanking you in advance for your time Dr. Hruban.

  8. Dr. Ralph Hruban Says:

    Chris- I am not too sure I know what you mean by “exhibits irregular cells in the pancreas,” but let me give it a try. Sometimes when there is lots of inflammation (something that occurs with pancreatitis), the cells in the pancreas can look “reactive” under the microscope. These cells are not cancerous, but exhibit some of the microscopic changes associated with cancer, but they are not cancer. Perhaps this is what you mean. My sincere best wishes to you. RHH

  9. Dr. Ralph Hruban Says:

    Helen- With your family history you may wish to see a trained cancer genetics counselor. Jennifer Axilbund is the cancer genetics counselor here at Johns Hopkins (solleje@jhmi.edu). You may also wish to join the National Familial Pancreas Tumor Registry. This is a research registry (not clinical care). Emily Palmisano can help you register (http://pathology.jhu.edu/pancreas/NFPTR/index.php). As to your question about floating stools. A lot of things can cause this, not only tumors. For example, chronic pancreatitis can decrease the digestive enzymes released by the pancreas. As a result, foods in our intestine are digested differently, and the stools may float. I would not be alarmed since you have had this for ten years, but certainly something to discuss with your primary care provider. RHH

  10. Quit Smoking Says:

    This is a great article. My grand daddy is terminal with cancer and he was a smoker for many years, and I guess to some extent obese as well. Although nothing can save him now, it helps a little to understand more about the disease.

  11. nancy amato Says:

    dr. hruban,
    i was diagnosed in sept. 2006 with adeno. before surgery they biopsied a lesion on my liver and the frozen section was negative, so they proceeded with the whipple. the final path report came back positive in the liver. so i don’t “fit in any category…stage 4 with a whipple.
    had gemzar, cisplatin, xeloda for 3 months followed by radiation. i am now in the vaccine trial at hopkins and being followed by that awesome dan laheru!
    i feel great and never quit work thru all this (i’m a CRNA) my question is this…after doing some reading on these sites, so many are treated with chemo for a much longer time than i was. is that because my scans were clean or do you think that was the protocol where i was treated? i was treated (very well, i must add) at university of michigan.
    i’ll be back at JH at the end of february for another vaccine.
    thanks for this chance to ask questions and all the great info on this site.


  12. yatindra nath yadav Says:

    dear sir

    recently i came to know that my mom has an cyst near the portal veian just near to pancreatic gland ,the doctors have taken the ultrasound and city scan and they are diagonising it might be cancer might not be cancer right now ther are not sure so kindly assist me

  13. Dr. Ralph Hruban Says:

    yatindra nath yadav:
    I am sorry to hear of your mother’s illness. Some cysts in the pancreas are harmless (benign) and others can contain a cancer (malignant). A combination of imagining (ultrasound and CT scans) can usually help narrow it down. In some instances a small biopsy can be taken. I would suggest that, if possible, your mother should be evaluated by a physician with experience in this area. If you would like to read more, we have a previous blog post on “intraductal papillary mucinous neoplasms,” one of the tumors of the pancreas that can form a cyst. If your mother would like to be evaluated by one of the experienced pancreas surgeons here at Johns Hopkins, simply directly contact one of the surgeons listed in the For Patients section of this web page. My sincere best wishes to you and to your mother. Dr. Hruban

  14. Tami Says:

    Thank you so much for the article and also for the blog. It is very helpful. My mother was recently diagnosed with pancreatic cancer, and is currently going through chemo at JH, in hopes to shrink the tumor enough to make it operable. I was curious about the vacine. Is this a last resort if the tumor is inoperable, I am a little confused about this.

  15. Dr. Ralph Hruban Says:

    Tami- I am sorry to hear of your mother’s illness. I certainly wish your mother and your family the best. The vaccine is an experimental vaccine used in specific clinical trials. Dr. Laheru and his team here at Hopkins would know best if your mother qualifies for one of these clinical trials. Dr. Hruban

  16. joseane Says:

    Sir doctor

    Minha Mãe era uma pessoa totalmente livre de Doenças até aos 76 anos de idade ,de janeiro a junho de 2008 estava em plena forma,mas apartir de julho de 2008 começou a sentir dores no lado esquerdo da Costela,houve dois meses para os especialistas diagnosticarem como Cancer ,pois eles achavam que era Síndrome do Intestino Irritável,e assim o diagnostico foi tardio,pois o tumor estava em 3 cm.
    Em junho ela usou um medicamento chamado AClasta(reposição para osteoporose),pois ela sempre vivia com acompanhamento Médico com O Geriatra,será que este medicamento fez alguma reação no Pancreas dela?
    pois ,antes de ela tomar esse medicamento ,os exames dela eram todos normais.
    Ela não sobreviveu a este maldito cancer.

  17. Dr. Ralph Hruban Says:

    I am sorry to hear about your mother. It is unlikely that her cancer was caused by the medication she was taking as most cancers take many months if not years to develop. Of not, Dr. Kern here at Johns Hopkins has shown that some anti-malarial drugs effect the p53 gene and we have heard of patients who first developed symptoms after taking one of these drugs (presumably the drug caused the existing cancer to exhibit symptoms). My sincere best wishes to you and your mother. Dr. Hruban

  18. Steve Harold Says:

    Thanks for such a readable article. I help many people to stop smoking and knowing that smoking is the highest cause of pancreatic cancer will form a part my education of patients

  19. Sasha Says:

    My mom was diagnosed with pancreatic cancer 29 months ago. She did chemo for a little bit at first but then decided on quality rather than quantity. Now she went back to St. Louis (2nd time) to see the doctor that origanally diagnosed her and he wants a blood test ran because it could be acute pancreatitis. Is it possible that she was misdiagnosed and after this long there is a chance that it’s pancreatitis? I hate to get my hopes up again!

  20. Dr. Ralph Hruban Says:

    I am sorry to hear about your mother. There is a rare form of pancreatitis called “lymphoplasmacytic sclerosing pancreatitis” that can mimic pancreatic cancer. The blood test for this would be a serum IgG4 test. This would be good news indeed, as some patients with lymphoplasmacytic sclerosing pancreatitis respond to treatment with steroids. Let me know how it goes, Dr. Hruban

  21. Miss Siv Hartvigsen Says:

    Dear Doctor,
    I’m writing to you for advise for my self. I’ve suffered from abdominal discomfort for about a year, to quite badly at times the last 6 months where I’ve had chestpains/upper abdominal pains/back pains, and with investigations they found little exept for an unexpected low density cyst in october on CT scan, this was reim. in december and mes. 5,2×4,8×1,4cm I was scheduled for EUS & biopsy, but they could not reach it as it lays posterior pancreas. Amalyse neg. and CA 19-9 neg. Ideally they want to do an MRI, but because I have a spinal cord stimulator (have RSD/CRPS) I can’t have MRI imaging. The doctor tells me that judging from the CT image it looks bengin, and that a biopsy/surgery is to risky due to its location? I continue to have abdominal symtoms, and I have lost 23 KG since August, however I know that I’ve also stopped started other meds. so I guess that could be the case… but should I be happy with a new CT in 6 months??? I know I’m a young contender for anything maligant re. pancreas, but high rate of cancer in family… I had CIN II many years ago, my dad is currently dying of head/neck cancer, and my grandfather died of cancer of the panceas. I trust your opinion, and in advance,- Thank you. Kind Regards, Siv Woman 37,

  22. Medha Says:

    Hi Dr.
    My father in law was operated was pancreatic cancer a month back. They have removed his drains last week. He has lost a lot of weight. Could you please suggest as to what he should be eating so that he gains weight ?

  23. ron shan Says:

    Dr. How long is a typical pancreatic cancer growing before it is detected or causes noticable symptoms? years? months?

  24. ron Says:

    Dr. Are there any early signs or symptoms of pancreatic cancer that patients have mentioned after being diagnosed, that they noticed in retrospect months or years earlier that may have been connected to their disease.

  25. Cassandra Says:

    Thank you so much for this write up it was very helpful and inportant for me to better understand what i went through. i am a 34 year old woman who was diagnosed with stage 1 pancreatic cancer May of 2006 after chemo treatment was over and test was taken the Oncologist told me that i have a good outlook however i still worry if it will come back and what will be my survival rate. i just think about my daughters which are 9 and 6. I would like to get involved with the community and and speak about what i went through and be there to educate and help others. how do i get started i live in Laurel, MD. THANK YOU

  26. Dr. Hruban Says:

    Ron: You ask good questions. Pancreatic cancers appear to arise from small precancerous lesions called PanIN lesions. Just as colon cancers can arise from colon polyps, so too can pancreatic cancer arise from these precursor lesions. It is not known how long these lesions are there before a cancer develops because they are too small to see using currently available technologies, but they are probably there for years before a cancer develops.
    As to your second question, the symptoms are as listed on this web site. Some people do develop new onset diabetes mellitus (sugar diabetes) before they are recognized to have pancreatic cancer. The challenge is that diabetes is actually fairly common, and clearly only a small minority of adults with new onset diabetes develop cancer. Dr. Hruban

  27. Dr. Hruban Says:

    I am sorry to hear of your diagnosis. You are very young to have pancreatic cancer. I am certainly glad to hear you are doing well. One way you can help is to join research studies such as the National Familial Pancreas Tumor registry (NFPTR) at Johns Hopkins. There is more information on the NFPTR available on this web site (http://pathology.jhu.edu/pancreas/nfptr/index.php). My sincere best wishes to you. Dr. Hruban

  28. Romona Weston Says:

    My father-in-law passed away almost 30 years ago from this. I will bookmark this page for my husband to read.

    Thank you.

  29. Stuart Brown Says:

    Thanks for the interesting article Dr Hruban. I just stumbled across it today. It is fascinating how good diets, keeping trim and raising the amount of fruit and vegetables we eat is linked to helping out with so many different medical conditions.

    I myself have recently completed a book about lowering cholesterol (http://www.cholesterolrevitaliser.com) and reading through the different scientific papers and literature on the subject whilst researching it made a compelling case for heavy focus in public health campaigns on improving diet.

    As you said in the article, there are of course many factors such as genetics, age, race etc that play significant parts with pancreatic cancer and other health conditions. But it is also good to be reminded that there are a many factors that are in our own hands, and that all of us have to actively help ourselves as much as we can when it comes to our own health.

  30. EEWing Says:

    Dear Doctor,
    When being treated with Gemzar chemo, how many treatments are necessary before you can tell if the body is responding? My sister has Stage IV pancreatic cancer that has spread to her liver. And they are saying after one treatment that her body is not responding. I would have thought she would need to have at least one cycle. Am I wrong?


  31. Dr. Hruban Says:

    I am sorry to hear about your sister’s illness. A BLOG is probably not the best forum to answer your questions about her treatment. I would suggest you speak with her oncologist. My sincere best wishes to you both.
    Dr. Hruban

  32. Dr. Ralph Hruban Says:

    I am glad to hear you are doing so well! I am also glad to hear that you want to get involved. There are several ways you can help. You could partner with others in your area, or you could try to launch out on your own. Give me a call when you have a minute and we can discuss more. My sincere best wishes, Dr. Hruban (410-955-2163, rhruban@jhmi.edu, http://pathology.jhu.edu/pancreas)

  33. Dr. Ralph Hruban Says:

    Ron- good question. A few that come to mind are new onset diabetes and unexplained back pain. Remember that these symptoms are common and the vast majority of people with diabetes and back pain do NOT have pancreatic cancer! Dr. Hruban (http://pathology.jhu.edu/pancreas)

  34. backsp4ce Says:

    My father-in-law passed away almost 30 years ago from this. I will bookmark this page for my husband to read.