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All the cells in the body contain DNA (deoxyribonucleic acid). DNAisthe molecule in the cell nucleus that carries the instructions for making living organisms. 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.
The DNA mutations that cause pancreatic cancer may be either inherited from a parent or acquired. Inherited mutations are carried in the DNA of aperson’s reproductive cells and can be passed on to that person’s children. Not everyone who has an inherited mutation will develop pancreatic cancer.
Acquired mutations are ones that develop during a person’s lifetime, either as random mutations in DNA or in response to injuries from harmful environmental factors such as exposure to radiation or chemicals.2,4 Scientists believethat most cancers result from complex processes that occur both among many different genesand between genes and outside factors.Some of these outside factors are called risk factors. Not everyone who has an acquired mutation will develop pancreatic carcinoma.
CAUSES RISK FACTORS FOR PANCREATIC CANCER
• 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
There is a long list of risk factors for pancreatic cancer (Box 2-1). Risk factorsarecharacteristics, habits, or environmental exposures that have been shown to increase the odds of developing a disease.
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 section 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.
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.
Diet. Adiet 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.
Obesity. People who are significantly overweight are 20 times more likely to develop pancreatic cancer compared with those who are not overweight.
Age. As people age, their risk of pancreatic cancer increases. Pancreatic cancer mostly affects people 55 years of age and older.
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.
Medical Factors.The incidence of pancreatic cancer is higher in people who have any of the following medical conditions:
• 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.
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. Incontrast, some people who do not haverisk 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.
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.8Not everyone with a family history of pancreatic cancer will develop the disease.
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. Researchers in the United States have set up national pancreatic cancer registries to study the hereditary factors that influence pancreatic cancer. (See the Appendix for more information and a list of registries.)
Relatives of patients with pancreatic cancer havean 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. Not everyone who has one of these mutations will develop pancreatic cancer.
The hereditary syndromes listed below may be associated with the development of pancreatic cancer.
Familial Breast Cancer Syndrome. People who havethe breast cancer 2gene (BRCA2)mutation have an increased risk of several cancers, among them pancreatic adenocarcinoma. The BRCA2gene 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 areasymmetrical and raised.
Peutz-Jeghers Syndrome (PJS). In people with PJS, the risks of gastrointestinal tumors such as esophageal, small bowel, colorectal, and pancreatic cancer areincreased. Polyps in the small intestine and dark spots on the mouth and fingers characterize the disease.
Hereditary Pancreatitis. Hereditary pancreatitis is a rare disease in which patients develop recurrent episodes of severechronic pancreatitis at an early age.3This 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.
Multiple Endocrine Neoplasia Type 1 Syndrome (MEN1; Wermer’s Syndrome). 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.
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 BRCA2gene, which is found in about one percent of Ashkenazi Jews, is responsible for a 10-fold increased risk of developing pancreatic cancer. Adefect in the BRCA1gene, which is found in 1.5 percent of Ashkenazi Jews, is responsible for a twofold increased risk.Doctors can test for the presence of these genetic mutations. Not everyone who has one of these inherited genetic mutations will develop cancer.
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