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What are the risk factors for pancreatic cancer?

A risk factor is anything that affects your chance of getting a disease such as cancer. Different cancers have different risk factors. Some risk factors, like smoking, can be changed. Others, like a person's age or family history, can't be changed. But risk factors don't tell us everything. Having a risk factor, or even several risk factors, does not mean that you will get the disease. And many people who get the disease may not have had any known risk factors. Researchers have found several factors that affect a person's chance of getting cancer of the pancreas. Most of these are risk factors for exocrine pancreatic cancer.

The risk of developing pancreatic cancer increases as people age. Almost all patients are older than 45. Nearly 90% are older than 55 and more than 70% are older than 65. The average age at the time of diagnosis is 72.

Men are slightly more likely to develop pancreatic cancer than women. This may be due, at least in part, to increased tobacco use in men. The difference in pancreatic cancer risk was more pronounced in the past (when tobacco use was much more common among men than women), but the gap has closed in recent years.

African Americans are more likely to develop pancreatic cancer than whites. The reasons for this are not clear, but it may be due in part to higher rates of smoking and diabetes in men and being overweight in women.

Cigarette smoking
The risk of getting pancreatic cancer is 2 to 3 times higher among smokers. Scientists think this may be due to cancer-causing chemicals in cigarette smoke that enter the blood and damage the pancreas. About 20% to 30% of exocrine pancreatic cancer cases are thought to be caused by cigarette smoking.  People who use smokeless tobacco are also more likely to get exocrine pancreatic cancer.

Obesity and physical activity
Very overweight (obese) people are more likely to develop exocrine pancreatic cancer, as are people who don't get much physical activity. Exercise lowers the risk of this cancer.

Exocrine pancreatic cancer is more common in people with this disease. The reason for this link is not known. Most of the risk is found in people with type 2 diabetes. This type of diabetes most often starts in adulthood. It is often related to being overweight or obese. It is not clear if people with type 1 (juvenile) diabetes have a higher than average risk. In some patients, though, the cancer seems to have caused the diabetes (not the other way around).

Chronic Pancreatitis
Chronic Pancreatitis is a long-term inflammation of the pancreas. This condition is linked with an increased risk of pancreatic cancer, but most patients with Pancreatitis never develop pancreatic cancer. The link between chronic Pancreatitis and pancreatic cancer is strongest in smokers.
A small number of cases of chronic Pancreatitis appear to be due to an inherited gene mutation (see "Family history"). People with this inherited form of chronic Pancreatitis seem to have a high lifetime risk for developing pancreatic cancer (about 40% to 75%).

Cirrhosis of the liver
Cirrhosis is a scarring of the liver. It develops in people with liver damage from things like hepatitis and alcohol use. People with cirrhosis seem to have an increased risk of pancreatic cancer.

Occupational exposure
Heavy exposure at work to certain pesticides, dyes, and chemicals used in metal refining may increase the risk of developing pancreatic cancer.

Family history
Pancreatic cancer seems to run in some families. In some of these families, the high risk is due to an inherited syndrome (explained in the next section, "Genetic syndromes"). In other families, the gene causing the increased risk of pancreatic cancer is not known.

Genetic syndromes
Inherited gene mutations are abnormal copies of certain genes that can be passed from parent to child. These abnormal genes may cause as many as 10% of pancreatic cancers and can cause other problems as well. Examples of the genetic syndromes that can cause exocrine pancreatic cancer include:
1.Hereditary breast and ovarian cancer syndrome, caused by mutations in the gene BRCA2
1.Familial melanoma, caused by mutations in the gene p16
2.Familial pancreatitis, caused by mutations in the gene PRSS1
3.Hereditary non-polyposis colorectal cancer (HNPCC), most often caused by a defect in either the gene MLH1 or the gene MSH2. At least 5 other genes can also cause HNPCC: MLH3, MSH6, TGBR2, PMS1, and PMS2. This disorder is also known as Lynch syndrome.
4.Peutz-Jeghers syndrome (PJS), caused by defects in the gene STK1. This syndrome is also linked with polyps in the digestive tract and several other cancers
5.Von Hippel-Lindau syndrome, caused by mutations in the gene VHL, can lead to an increased risk of pancreatic cancer and carcinoma of the ampulla of Vater

Pancreatic neuroendocrine tumors and cancers can also be caused by a genetic syndrome, such as:

1.Neurofibromatosis, type 1, which is caused by mutations in the gene NF1. This syndrome leads to an increased risk of many tumors, including somatostatinomas.
2.Multiple endocrine neoplasia, type 1, caused by mutations in the gene MEN1, leads to an increased risk of tumors of the parathyroid gland, the pituitary gland, and the islet cells of the pancreas.

Scientists have found the genes that cause the syndromes listed above and they can be recognized by genetic testing. For more information on genetic testing, see the section, “Can pancreatic cancer be found early?”

Stomach problems
Infection of the stomach with the ulcer-causing bacteria Helicobacter pylori (H. pylori) may increase the risk of getting pancreatic cancer. Some researchers believe that excess stomach acid may also increase the risk.

Some studies linked pancreatic cancer and diets high in fat, or those that include a lot of red meat, pork, and processed meat (such as sausage and bacon). Others have found that diets high in fruits and vegetables may help reduce the risk of pancreatic cancer. But not all studies have found such links, and the exact role of diet in relation to pancreatic cancer is still being studied.

Some older studies have suggested that drinking coffee might increase the risk of pancreatic cancer, but more recent studies have not confirmed this.

Most studies have not found a link between alcohol use and pancreatic cancer. But heavy alcohol use can raise the risk of diabetes, liver cirrhosis, an

What are the key statistics about pancreatic cancer?

The American Cancer Society's most recent estimates for pancreatic cancer in the United States are for 2012:
1.About 43,920 people (22,090 men and 21,830 women) will be diagnosed with pancreatic cancer.
2.About 37,390 people (18,850 men and 18,540 women) will die of pancreatic cancer
Since 2004, rates of pancreatic cancer have increased about 1.5% per year.
The lifetime risk of developing pancreatic cancer is about 1 in 71 (1.41%). This is about the same for men and women. A person's risk may be altered by certain risk factors.

The Normal Pancreas
The pancreas is an organ located behind the stomach. It is shaped a little bit like a fish with a wide head, a tapering body, and a narrow, pointed tail. It is about 6 inches long but less than 2 inches wide and extends horizontally across the abdomen. The head of the pancreas is on the right side of the abdomen (belly), behind the place where the stomach meets the duodenum (the first part of the small intestine). The body of the pancreas is located behind the stomach and the tail of the pancreas is on the left side of the abdomen next to the spleen.

The pancreas contains 2 different types of glands: exocrine and endocrine.
The exocrine glands make pancreatic "juice," which is released into the intestines. This juice contains enzymes that help you digest fats, proteins, and carbohydrates in the food you eat. Without these, some of the food you eat would just pass through your intestines without being absorbed. The enzymes are released into tiny tubes called ducts. These tiny ducts merge to form larger ducts that empty into the pancreatic duct. The pancreatic duct merges with the common bile duct (the duct that carries bile from the liver), and empties the pancreatic juice into the duodenum (the first part of the small intestine) at the ampulla of Vater. More than 95% of the cells in the pancreas are exocrine glands and ducts.

A small percentage of the cells in the pancreas are endocrine cells. These cells are arranged in small clusters called islets (or islets of Langerhans). The islets release important hormones, such as insulin and glucagon, directly into the blood. Insulin reduces the amount of sugar in the blood, while glucagon increases it. Diabetes results from a defect in insulin production.

Types of pancreatic tumors
The exocrine cells and endocrine cells of the pancreas form completely different types of tumors.

Exocrine tumors
Exocrine tumors are by far the most common type of pancreas cancer. When someone says that they have pancreatic cancer, they usually mean an exocrine pancreatic cancer. Benign (non-cancerous) cysts and benign tumors called cystadenomas can occur, but most pancreatic exocrine tumors are malignant (cancerous).

An adenocarcinoma is a cancer that starts in gland cells. About 95% of cancers of the exocrine pancreas are adenocarcinomas. These cancers usually begin in the ducts of the pancreas, but they sometimes develop from the cells that make the pancreatic enzymes (acinar cell carcinomas).
Less common types of ductal cancers of the exocrine pancreas include adenosquamous carcinomas, squamous cell carcinomas, and giant cell carcinomas. These types are distinguished from one another based on how they look under the microscope.

The treatment of an exocrine pancreatic cancer is mostly based on the stage of the cancer, not its exact type. The stage of the cancer describes how large the tumor is and how far it has spread. Pancreatic cancer staging is described later in this document.

A special type of cancer, called ampullary cancer (or carcinoma of the ampulla of Vater) deserves mention here. The place where the bile duct and pancreatic duct come together and empty into the duodenum is called the ampulla of Vater. Cancers that start here are called ampullary cancers. These cancers often block the bile duct while they are still small and have not spread far. This blockage causes bile to build up in the body, which leads to yellowing of the skin and eyes (jaundice) and can turn the urine dark. This is an easily recognized sign that something is wrong. This is why ampullary cancers are usually found at an earlier stage than most pancreatic cancers, which means they usually have a better prognosis (outlook) than typical pancreatic cancers.
Ampullary cancers are included with pancreatic cancer in this document because their treatments are very similar.

Endocrine tumors
Tumors of the endocrine pancreas are uncommon. As a group, they are known as pancreatic neuroendocrine tumors (NETs), or sometimes as islet cell tumors. There are several subtypes of islet cell tumors. Each is named according to the type of hormone-making cell it starts in:
1.Insulinomas come from cells that make insulin.
2.Glucagonomas come from cells that make glucagon.
3.Gastrinomas come from cells that make gastrin.
4.Somatostatinomas come from cells that make somatostatin.
5.VIPomas come from cells that make vasoactive intestinal peptide (VIP).
6.PPomas come from cells that make pancreatic polypeptide.

Carcinoid tumors are another type of pancreatic NET. These tumors often make serotonin (also called 5-HT) or its precursor, 5-HTP.

About half of pancreatic NETs make hormones that are released into the blood and so are called functioning tumors. Tumors that do not make hormones are called non-functioning.
Islet cell tumors can be benign or malignant. Benign tumors are called pancreatic neuroendocrine tumors, while malignant tumors are called pancreatic neuroendocrine cancers or carcinomas. Malignant and benign tumors can look very similar under the microscope, so it isn't always clear at the time of diagnosis whether or not a NET is cancer. Sometimes the diagnosis only becomes clear when the tumor has spread outside of the pancreas.

Pancreatic neuroendocrine cancers make up less than 4% of all pancreatic cancers diagnosed. Treatment and prognosis depend on the specific tumor type and the stage (extent) of the tumor but the prognosis is generally better than that of pancreatic exocrine cancers. The most common types of pancreatic endocrine tumors are gastrinomas and insulinomas. The other types occur very rarely.

It is very important to distinguish between exocrine and endocrine cancers of the pancreas. They have distinct risk factors and causes, have different signs and symptoms, are diagnosed using different tests, are treated in different ways, and have different prognoses. In this document, the term pancreatic neuroendocrine tumor is used for both benign and malignant endocrine pancreatic tumors.



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