by Dr. C.H. Weaver M.D. updated 9/2020
Information about the prevention of pancreatic cancer and the science of screening appropriate individuals at high risk of developing cancer is gaining interest. Physicians and individuals alike recognize that the best “treatment” of cancer is preventing its occurrence in the first place or detecting it early when it may be most treatable. (2)
Over the past several decades, the incidence of pancreatic cancer has been increasing and the disease is now the fifth leading cause of cancer death in the United States. Pancreatic cancer accounts for approximately 2% of all newly diagnosed cancers in the United States each year, but 5% of all cancer deaths. Pancreatic cancer is often called a silent killer because it usually does not cause any recognizable symptoms until it is advanced and has spread outside the pancreas. As a result, the majority of pancreatic cancers are not diagnosed until they have reached advanced stages and are considered incurable.
The chance of an individual developing cancer depends on both genetic and non-genetic factors. A genetic factor is an inherited, unchangeable trait, while a non-genetic factor is a variable in a person’s environment, which can often be changed. Non-genetic factors may include diet, exercise, or exposure to other substances present in our surroundings. These non-genetic factors are often referred to as environmental factors. Some non-genetic factors play a role in facilitating the process of healthy cells turning cancerous (i.e. the correlation between smoking and lung cancer) while other cancers have no known environmental correlation but are known to have a genetic predisposition, meaning a person may be at higher risk for a certain cancer if a family member has that type of cancer.
Heredity or Genetic Factors
Hereditary associations account for a small fraction of the total number of cases of pancreatic cancer. Only 7 to 8% of patients with pancreatic cancer have one or more family members with pancreatic cancer. Some other inherited syndromes are associated with an increased incidence of pancreatic cancer, including familial adenomatous polyposis, familial atypical multiple mole melanoma and hereditary pancreatitis. Forty percent of patients with hereditary pancreatitis develop pancreatic cancer by the age of 70. The risk of developing pancreatic cancer is approximately 75% if the pattern of inheritance is through the father. Researchers have identified two gene mutations in families with hereditary pancreatitis. This discovery has helped to allow for screening in families with a history of familial pancreatitis. (2)
Lynch Syndrome, an inherited cause of colorectal cancer that also increases the risk of several types of cancer including pancreatic cancer. It results from inherited mutations in genes involved in DNA mismatch repair. These mutations greatly increase the risk of developing colorectal cancer and also increase the risk of several other cancers.
The risk of pancreatic cancer in families with Lynch Syndrome was 1.31% by the age of 50 and 3.68% by the age of 70. This risk is more than eight times higher than the risk in the general U.S. population. (8)
Environmental or Non-Genetic Factors
Although the causes of pancreatic cancer remain ambiguous, researchers have identified some risk factors that are associated with pancreatic cancer; however, these environmental factors do not account for the majority of cases.
Cigarette Smoking: The most consistent risk factor associated with pancreatic cancer is cigarette smoking. Cigarette smokers are two to three times more likely to develop pancreatic cancer than nonsmokers. Approximately 30% of pancreatic cancers are believed to directly result from smoking.
Age: Research indicates that the risk of pancreatic cancer increases with age. The average age at diagnosis is 70. People under 40 rarely develop pancreatic cancer.
Diet: The results of several clinical studies indicate that individuals who consume a diet high in fat and low in fruits and vegetables and dietary folate may be at an increased risk of pancreatic cancer. Some researchers have reported an association between meat and fish consumption and the risk of pancreatic cancer. This may be related to the carcinogenic and mutagenic effects of heterocyclic aromatic amines present in cooked meat and fish. (5)
Obesity: Research indicates that individuals who are obese are at an increased risk for developing pancreatic cancer. Researchers used data from two United States cohort studies to evaluate the relationship between obesity, physical activity and the risk of pancreatic cancer. The study involved 46,648 men ages 40 to 75 and 117,041 women ages 30 to 55, with10-20 years of follow-up. The results indicated that individuals with a higher body mass index (BMI) had an increased risk of pancreatic cancer compared with individuals with a lower BMI. Furthermore, moderate activity reduced the risk of pancreatic cancer, especially among individuals with a high BMI.
Occupational exposure: Some studies suggest that exposure to petroleum and other chemicals might increase the risk of pancreatic cancer. Petrochemical workers, hairdressers and rubber workers appear to be at an increased risk of pancreatic cancer.
Pancreatitis: Chronic pancreatitis refers to a long-term inflammation of the pancreas. Patients with non-hereditary chronic pancreatitis appear to have an increased incidence of pancreatic cancer; however, the majority of individuals with chronic pancreatitis never develop pancreatic cancer.
Diabetes: There is an increased incidence of pancreatic cancer among patients with diabetes. Individuals with diabetes develop pancreatic cancer twice as often as those who do not have diabetes. Onset of diabetes may herald the appearance of pancreatic cancer, particularly if the diabetes occurs during or beyond age 50. Diabetes is present in 60-80% of patients with pancreatic cancer and the majority of patients were diagnosed within 2 years of the cancer. Patients with diabetes and cancer more often do not have a family history of diabetes. It appears that a subgroup of patients with late onset diabetes who have no family history of diabetes may be at an increased risk. Abnormalities of glucose metabolism in individuals who do not have diabetes are also associated with an increase in pancreatic cancer.
Screening and Early Detection of Pancreatic Cancer
For many types of cancer, progress in the areas of cancer screening and treatment has offered promise for earlier detection and higher cure rates. The term screening refers to the regular use of certain examinations or tests in individuals who do not have any symptoms of a cancer but are at high risk for that cancer. When individuals are at high risk for a type of cancer, this means that they have certain characteristics or exposures, called risk factors that make them more likely to develop that type of cancer than those who do not have these risk factors. The risk factors are different for different types of cancer. An awareness of these risk factors is important because 1) some risk factors can be changed (such as smoking or dietary intake), thus decreasing the risk for developing the associated cancer; and 2) persons who are at high risk for developing a cancer can often undergo regular screening measures that are recommended for that cancer type. (2)
Pancreatic cancer has a high mortality rate because it is difficult to find the disease early. Pancreatic cancer usually does not cause any recognizable symptoms until it is advanced and has spread outside the body. Since the pancreas is deep inside the body, it is difficult to detect tumors during a routine check-up. Currently, there are no screening tests to find this disease early in individuals who have no symptoms.
For other types of cancer like breast or prostate cancer, significant progress in the areas of cancer screening has offered promise for earlier detection and higher cure rates. The term screening refers to the regular use of certain examinations or tests in individuals who do not have any symptoms of a cancer but are at high risk factors for developing that cancer which makes them more likely to develop that type of cancer than those who do not have these risk factors.
Pancreatic Cancer Early Detection and Prevention Center at NYU-Langone
NYU in partnership with the University of Michigan Rogel Cancer Center have developed a tool that includes questions about an individual’s health and family history that can help determine if they have genetic risk factors for pancreatic cancer. At risk individuals can undergo additional testing to define their risk and determine if routine screening can be beneficial.
The pancreatic cancer risk assessment tool.
What are the risk factors for Pancreatic Cancer?
Individuals with two or more family members with pancreatic cancer are considered to be a higher risk of developing pancreatic cancer and genetic testing may be an important tool for cancer screening and early detection. In addition, if at least one person in a family has had pancreatic cancer, additional risk factors include the following:
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- a family member with breast cancer before age 50 or multiple family members with breast cancer at any age
- a family member with ovarian cancer
- a family member with colon or uterine cancer before age 50, or multiple family members with colon or uterine cancer
- more than one family member with malignant melanoma.
Individuals are also considered at higher risk if a genetic test shows a genetic mutation for a disease that is associated with pancreatic cancer, especially if a family member had pancreatic cancer. These gene mutations include the following:
- BRCA1, BRCA2 (breast and ovarian cancer)
- ATM, PALB2 (breast cancer)
- CDKN2A (melanoma)
- MLH1, MSH2, MSH6, PMS2, EPCAM (Lynch syndrome)
- STK11 (Peutz-Jeghers syndrome)
For people at an increased risk of pancreatic cancer, based on family history or genetic test results, doctors may perform annual tests to detect developing cancers earlier when they are more treatable.
Currently, computerized tomography (CT) scans are the best way to detect small pancreatic cancers. Endoscopic ultrasound will detect small pancreatic cancers not detected by CT scans, and the cancer marker CA 19-9 is sometimes elevated in early cases of pancreatic cancer. There are however no specific recommendations for screening people who are at a high risk for pancreatic cancer. However, one strategy would be to perform a screening CT for persons with familial syndromes associated with an increased risk of pancreatic cancer.
Doctors have constructed a panel of biomarkers to detect pancreatic cancer combing extracellular vesicles, cell-free DNA (cfDNA) and the CA19-9 protein, all of which can be obtained with a blood sample.
- Extracellular vesicles recently were discovered to be shed from tumor and other tissue in the bodies of patients with cancer. They circulate in blood and thus are easily obtainable with a simple blood draw. Importantly, they have been shown to provide a means for cells to communicate with each other and may play a functional role in the development and progression of small tumors. Extracellular vesicles are known to contain RNA, DNA and proteins that are representative of the tumor cells from which they were shed, meaning they provide a way of “sampling” the tumor without having to perform an invasive biopsy.
- Cell-free DNA (cfDNA) circulating in a patient’s blood by extracting the DNA and measuring its concentration. This simple measure of the amount of total cfDNA in blood often correlates with a patient with cancer’s disease burden, as well as prognosis. Next, we performed a droplet digital PCR (ddPCR) analysis on the cfDNA to identify mutations in the gene KRAS that are found in most pancreatic tumors. We then used the ddPCR results to measure the proportion of the total cfDNA that likely came from the tumor, also known as KRAS allele fraction. This also has been correlated with disease burden and worse outcome.
- CA19-9, which typically is measured in clinical blood work for patients with pancreatic cancer. However, one of the limitations of the CA19-9 test is that not all patients with pancreatic cancer will have detectable amounts of the protein. We reasoned that a multi-analytic approach, combining extracellular vesicles, DNA, and CA19-9, would provide a more comprehensive and accurate picture of the patient’s disease than any one analysis alone.
- Endoscopic Ultrasound During an endoscopic ultrasound, sound waves are used to create images of the pancreas that are viewed on a computer monitor. In this test, an echoendoscope, which is a thin tube attached to an ultrasound probe, is placed in a person’s mouth after sedation and advanced to the small intestine where the pancreas is viewed.
- Magnetic Resonance Cholangiopancreatography Magnetic resonance cholangiopancreatography, magnetic fields and radio waves produce detailed, three-dimensional images of the pancreas and bile ducts. These MRI scans are usually performed in an enclosed machine.
Prevention of Pancreatic Cancer
Cancer is largely a preventable illness. Two-thirds of cancer deaths in the U.S. can be linked to tobacco use, poor diet, obesity, and lack of exercise. All of these factors can be modified. Nevertheless, an awareness of the opportunity to prevent cancer through changes in lifestyle is still under-appreciated. (2)
Since the development of pancreatic cancer is poorly understood, it is difficult to make recommendations for prevention. Currently, the best approach is to avoid the risk factors for this disease and modify diet and lifestyle.
Avoid Smoking: Since cigarette smoking is responsible for 30% of pancreatic cancers, it would be wise to avoid or quit smoking.
Diet: Diet is a fertile area for immediate individual and societal intervention to decrease the risk of developing certain cancers. Numerous studies have provided a wealth of often-contradictory information about the detrimental and protective factors of different foods.
There is convincing evidence that excess body fat substantially increases the risk for many types of cancer. While much of the cancer-related nutrition information cautions against a high-fat diet, the real culprit may be an excess of calories. Studies indicate that there is little, if any, relationship between body fat and fat composition of the diet. These studies show that excessive caloric intake from both fats and carbohydrates lead to the same result of excess body fat. The ideal way to avoid excess body fat is to limit caloric intake and/or balance caloric death in men in the United intake with ample exercise.
It is still important, however, to limit fat intake, as evidence still supports a relationship between cancer and polyunsaturated, saturated and animal fats. Specifically, studies show that high consumption of red meat and dairy products can increase the risk of certain cancers. One strategy for positive dietary change is to replace red meat with chicken, fish, nuts and legumes.
High fruit and vegetable consumption has been associated with a reduced risk for developing at least 10 different cancers. This may be a result of potentially protective factors such as carotenoids, folic acid, vitamin C, flavonoids, phytoestrogens and isothiocyanates. These are often referred to as antioxidants.
There is strong evidence that moderate to high alcohol consumption also increases the risk of certain cancers. One reason for this relationship may be that alcohol interferes with the availability of folic acid. Alcohol in combination with tobacco creates an even greater risk of certain types of cancer.
While researchers have long evaluated the link between diet and all cancers, there also has been research to investigate the link between diet and pancreatic cancer. Recent studies have indicated that reducing intake of well-cooked meat and fish and increasing the intake of fruit and vegetables might be important for preventing pancreatic cancer. In addition, the results of a recent clinical study indicate that a high intake of dietary folate significantly reduces the risk of pancreatic cancer. Some rich sources of dietary folate are leafy greens, turnip greens, dry beans, peas and some fruits and vegetables.
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Exercise: Higher levels of physical activity may reduce the incidence of some cancers. According to researchers at Harvard, if the entire population increased their level of physical activity by 30 minutes of brisk walking per day (or the equivalent energy expenditure in other activities), we would observe a 15% reduction in the incidence of colon cancer.
- American Cancer Society: Cancer Facts and Figures 2017. Atlanta, Ga: American Cancer Society, 2017.
- NCNN Guidelines for Pancreatic Cancer
- Silverman DT, Schiffman M, Everhart J, et al.: Diabetes mellitus, other medical conditions and familial history of cancer as risk factors for pancreatic cancer. Br J Cancer 80 (11): 1830-7, 1999.**]**National failure to operate on early stage pancreatic cancer. Annals of Surgery. 2007;246:173-180.
- Tersmette AC, Petersen GM, Offerhaus GJ, et al.: Increased risk of incident pancreatic cancer among first-degree relatives of patients with familial pancreatic cancer. Clin Cancer Res 7 (3): 738-44, 2001.
- Nöthlings U, Wilkens LR, Murphy SP, et al.: Meat and fat intake as risk factors for pancreatic cancer: the multiethnic cohort study. J Natl Cancer Inst 97 (19): 1458-65, 2005.
- World Cancer Research Fund International. Pancreatic cancer statistics. Accessed February 2019 from here
- Lynparza First Promising New Drug to Treat Pancreatic Cancer in Years
- Kastrinos F, Mukherjee B, Tayob N et al. Risk of pancreatic cancer in families with Lynch Syndrome. Journal of the American Medical Association. 2009;302:1790-1795.