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What Causes Pancreatic Cancer?
GENES AND PANCREATIC CANCER | Risk Factors | Family History
All the cells in the body contain DNA (deoxyribonucleic acid). DNA is the molecule in the cell nucleus that carries the instructions
for making living organisms. 1 When cells grow and divide, they also copy DNA. Sometimes mistakes, called mutations, occur during this copying process.
Mutations in DNA occur frequently, especially when cells divide. Cells have an exceptional ability to repair these changes
in DNA. However, the DNA repair mechanisms also can fail. When they do, these mistakes in DNA can be passed along to future
copies of the altered cell. More abnormal cells then can be produced. When these abnormal cells continue to grow unchecked,
cancer may develop. 2
The DNA mutations that cause pancreatic cancer may be either inherited from a parent or acquired. 3 Inherited mutations are carried in the DNA of a person’s reproductive cells and can be passed on to that person’s children. 2 Not everyone who has an inherited mutation will develop pancreatic cancer.
RISK FACTORS
There is a long list of risk factors for pancreatic cancer (Box 2-1). Risk factors are characteristics, habits, or environmental exposures that have been shown to increase the odds of developing
a disease.
| Box 2-1 |
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RISK FACTORS FOR PANCREATIC CANCER 3-5
- Smoking
- Diet
- Obesity
- Age
- Race
- Family history
- Medical factors
- Chronic pancreatitis
- Diabetes
- History of stomach surgery (partial gastrectomy)
- Environmental exposure to certain chemicals
Not everyone with one or even more than one of these risk factors will develop pancreatic cancer.
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Research conducted by Theresa Pluth Yeo, PhD, MPH, ACNP, Program Director of the Advanced Practice Oncology Nursing Program at Jefferson, suggests that, in addition to the risk
factors outlined above in Box 2-1, exposure to second hand smoke, occupational asbestos, and environmental radon may increase the risk of pancreatic cancer.
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You can decrease some of your risk by maintaining a healthy body weight, eating a healthy diet that is high in fruits and
vegetables and low in processed meats, and not smoking. Some risk factors that you cannot influence are your age and family
history. Not everyone who has one or more of these risk factors will develop pancreatic cancer.
Risk Factors You Can Influence
Smoking. Smoking is a direct risk factor because people who smoke have two to three times the chance of getting pancreatic cancer
compared with people who do not smoke. 4
Diet. A diet high in cholesterol, fried foods, and processed meats, such as bacon and sausage, may increase the risk of pancreatic
cancer. A diet high in fruits and vegetables may reduce the risk of pancreatic cancer. 3,4
Obesity. People who are significantly overweight are 20 times more likely to develop pancreatic cancer compared with those who are
not overweight. 4
Other Risk Factors
Age. As people age, their risk of pancreatic cancer increases. Pancreatic cancer mostly affects people 55 years of age and older. 4
Race. In the United States, pancreatic cancer is more common in African Americans than in whites. The reasons are not clear. Differences
in dietary habits, the rates of obesity and diabetes, and the frequency of cigarette smoking exist between these groups. Genetic
or other unknown factors may also explain the higher incidence in African Americans. 5
Medical Factors.The incidence of pancreatic cancer is higher in people who have any of the following medical conditions 3,4:
- Chronic pancreatitis (inflammation that causes irreversible damage)
- Long-standing diabetes mellitus (high blood sugar)
- History of stomach surgery (partial gastrectomy)
Environmental Factors. Occupational exposure to some chemicals, such as pesticides, dyes, or chemicals related to gasoline, may increase the risk
for pancreatic cancer. 4
Presence of Risk Factors
When a person has any one or even more than one of these risk factors, it does not mean that the person is certain to develop
pancreatic cancer. In contrast, some people who do not have risk factors will still get pancreatic cancer. Researchers do not know the reasons
for these differences but are working to understand how lifestyle and environmental risks interact with individual genetic
makeup to influence the chances of developing pancreatic cancer. 4,6
FAMILY HISTORY AND PANCREATIC CANCER
Pancreatic cancer may be inherited because it tends to run in families. 4 This means that relatives of patients with pancreatic cancer may have an increased risk of developing the disease. One recent
study done in Iceland found that people who had one first-degree relative (parent, sibling, or child) with pancreatic cancer had two to three times the risk of developing pancreatic cancer compared
with people with no family history. 8 Not everyone with a family history of pancreatic cancer will develop the disease.
| FAMILIAL PANCREATIC CANCER |
Relatives of patients with pancreatic cancer have an increased risk of developing it. Inherited mutations in known cancer-causing
genes have been shown to be the cause of familial pancreatic cancer in some families. 7
Not everyone who has one of these mutations will develop pancreatic cancer.
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From 5 to 10 percent of pancreatic cancers result from hereditary factors. 2 Researchers believe that studying specific cancer genes may provide a better understanding of the causes of pancreatic cancer.
In turn, a better understanding of the causes may lead to more effective screening methods. 9,10 Researchers in the United States have set up national pancreatic cancer registries to study the hereditary factors that influence
pancreatic cancer.
See Services & Resources for more information and a list of registries
HEREDITARY SYNDROMES
The hereditary syndromes listed below may be associated with the development of pancreatic cancer. 11
Familial Breast Cancer Syndrome. People who have the breast cancer 2 gene (BRCA2)mutation have an increased risk of several cancers, among them pancreatic
adenocarcinoma. 12 The BRCA2 gene is particularly common in the Ashkenazi Jewish population.
Familial Atypical Multiple Mole Melanoma (FAMMM) Syndrome. People with FAMMM syndrome have many different-sized skin moles that are asymmetrical and raised. 11
Peutz-Jeghers Syndrome (PJS).In people with PJS, the risks of gastrointestinal tumors such as esophageal, small bowel, colorectal, and pancreatic cancer
areincreased. 13 Polyps in the small intestine and dark spots on the mouth and fingers characterize the disease.14
Hereditary Pancreatitis. Hereditary pancreatitis is a rare disease in which patients develop recurrent episodes of severe chronic pancreatitis at
an early age. 3 This is not the same as chronic pancreatitis.
Hereditary Nonpolyposis Colon Cancer (HNPCC; Lynch Syndrome). People with HNPCC have a higher than normal chance of developing colon, pancreatic, uterine, stomach, or ovarian cancer. 3
Multiple Endocrine Neoplasia Type 1 Syndrome (MEN1; Wermer’sSyndrome).MEN1 is a rare, inherited disorder that affects the endocrine glands and can cause tumors in the pancreas and other organs,
which usually are not cancerous. 11
| ASHKENAZI JEWS: ARE THEY AT RISK FOR PANCREATIC CANCER? |
Pancreatic cancer is more common in people of Ashkenazi Jewish ancestry. Researchers believe there is a genetic basis for
this increased risk. A defect in the BRCA2 gene,which is found in about one percent of Ashkenazi Jews, is responsible for
a 10-fold increased risk of developing pancreatic cancer. A defect in the BRCA1 gene,which is found in 1.5 percent of Ashkenazi Jews, is responsible for a twofold increased risk. 15 Doctors can test for the presence of these genetic mutations. Not everyone who has one of these inherited genetic mutations will develop cancer. |
REFERENCES ! Click reference number to return to text.
1. National Human Genome Research Institute. National Institutes of Health. Talking glossary of genetic terms. www.genome.gov/glossary.cfm.
Accessed April 13, 2007.
2. National Cancer Institute. Understanding cancer series: gene testing. www.cancer.gov/ cancertopics/understandingcancer/ genetesting.
Accessed April 13, 2007.
3. Johns Hopkins Pathology. Pancreatic cancer. http://pathology2.jhu.edu/ pancreas/causespc.cfm. Accessed April 11, 2007.
4. American Cancer Society. Pancreatic cancer. http://documents.cancer.org/ 116.00. Accessed April 14, 2007.
5. emedicine. Pancreatic cancer. www.emedicine.com/med/topic1712htm. Accessed May 14, 2007.
6. Familial pancreatic cancer. Ask an Expert. 2004;2:1-3.
7. Hruban RH, Petersen GM, Goggins M, et al. Familial pancreatic cancer. Ann Oncol. 1999;10(Suppl 4):69-7.
8. Amundadottir LT, Thorvaldsson S, Gudbjartsson DF, et al. Cancer as a complex phenotype: pattern of cancer distribution within
and beyond the nuclear family. PLoS Medicine. 2004: 1:229-36.
9. Hruban RH, Iocobuzio-Donahue C, Wilentz RE, et al. Molecular pathology of pancreatic cancer. Cancer J. 2001; 7:251-8.
10. Li D, Xie K, Wolff R, Abbruzzese JL. Pancreatic cancer. Lancet. 2004; 363:1049-57.
11. National Cancer Institute. Pancreatic cancer. 2005.
www.cancer.gov/ cancertopics/types/pancreatic. Accessed April 1, 2007.
12. Arnold MA, Goggins M. BRCA2 and predisposition to pancreatic and other cancers. Exp Rev Mol Med. 2001; www.expertreviews.org/0100309Xh.htm.
Accessed April 14, 2007.
13. Hearle N, Schumacher V, Menko FH, et al. Frequency and spectrum of cancers in the Peutz-Jeghers syndrome. Clin Cancer Res.
2006;12:3209-15.
14. National Cancer Institute. Dictionary of cancer terms. www.cancer.gov. Accessed April 13, 2007.
15. Johns Hopkins Pathology. Pancreatic cancer in individuals of Ashkenazi Jewish ancestry. http://pathology2.jhu.edu/ PANCREAS/ashkenazi_jewish_ancestry.cfm.
Accessed April 6, 2007.
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