Pancreatic cancer and genetics

ALSO KNOWN AS: Cancer of the pancreas

DEFINITION Pancreatic cancer is the growth of cancer cells in the pancreas. The pancreas is a long, flattened, pear-shaped organ in the abdomen. It makes digestive enzymes and hormones, including insulin.

Cancer occurs when cells in the body divide without control or order. If cells keep dividing uncontrollably, a mass of tissue forms. This is called a growth or tumor. The term cancer refers to malignant tumors. They can invade nearby tissue and spread to other parts of the body.

Risk Factors

Males and people who are forty years of age or older are at an increased risk for pancreatic cancer. Other risk factors include smoking and using smokeless tobacco, such as chewing tobacco; having diabetes; having chronic pancreatitis, hereditary pancreatitis, or familial nonpolyposis colon cancer syndrome; having a family or personal history of certain types of colon polyps or colon cancer; having a family history of pancreatic cancer, especially in Ashkenazi Jews with the BRCA2 (breast cancer associated) gene; and eating a high-fat diet.

Etiology and Genetics

While there is a substantial genetic component to the development of pancreatic cancer, the majority of new cases of the disease occur in families where there is no previous family history. However, several genes have been identified that are associated with an increased risk of pancreatic cancer. For example, mutations in the PRSS1 gene, found on the long arm of chromosome 7 at position 7q35, can cause hereditary pancreatitis, a condition that involves inflammation and swelling of the pancreas and severe abdominal pain. Affected individuals also have about a 40 percent risk of developing pancreatic cancer at some point in their adult years.

Most other cases of inherited pancreatic cancer result from mutations in any of several genes called tumor-suppressor genes, and these mutations can be inherited from either the male or female parent. Tumor-suppressor genes encode proteins that normally function in a variety of ways to limit or prevent cell growth and division. Mutations in these genes can lead to a loss in the ability to restrict tumor formation due to uncontrolled cell growth. When mutations occur in tumor-suppressor genes, it is not unusual to find that there is an increased risk for several different types of cancer to develop.

Peutz-Jeghers syndrome (PJS) is a rare condition in which affected individuals have multiple polyps in the digestive tract. People with PJS have about a 35 percent risk of developing pancreatic cancer, as well as an increased risk for skin, uterine, ovarian, breast, and lung cancers. Mutations in a single gene called STK11 (at position 19p13.3) are responsible for this condition.

The two genes most commonly associated with an increased risk of breast and ovarian cancer are BRCA1, found on the long arm of chromosome 17 at position 17q21, and BRCA2 (at position 13q12.3), yet mutations in these same two genes have also been linked to an increased risk of pancreatic cancer—about ten times greater than the average risk. These mutations are inherited in an autosomal dominant fashion, meaning that a single copy of the mutation is sufficient to cause the increased cancer risk. An affected individual has a 50 percent chance of transmitting the mutation to each of his or her children.

Individuals carrying a mutation that predisposes them to familial nonpolyposis colon cancer syndrome (Lynch syndrome) have been shown to have about an 8 to 10 percent risk of developing pancreatic cancer, a 20 to 50 percent risk of developing uterine cancer, and a 10 percent increased risk for ovarian cancer. Four different genes have been identified in which such mutations might occur: MLH1 (at position 3p21.3), MSH2 (at position 2p22-p21), MSH6 (at position 2p16), and PMS2 (at position 7p22).

Finally, there is a condition known as familial atypical multiple mole melanoma and pancreatic cancer (FAMMM-PC), which is associated with mutations in the CDKN2A gene (at position 9p21). Affected individuals have a 15 to 17 percent risk of developing pancreatic cancer and as much as a 70 percent risk of developing melanoma skin cancer.

Symptoms

Pancreatic cancer does not cause symptoms in its early stages. The cancer may grow for some time before it causes symptoms. When symptoms do appear, they may be very vague. In many cases, the cancer has spread outside the pancreas by the time it is discovered.

Symptoms will vary depending on the location and size of the tumor. Symptoms include nausea; loss of appetite; unexplained weight loss; pain in the upper abdomen, sometimes spreading to the back (a result of the cancer growing and spreading); jaundice—yellowness of skin and whites of the eyes; dark urine (if the tumor blocks the common bile duct); tan stool or stool that floats to the top of the bowl; and weakness, dizziness, chills, muscle spasms, and diarrhea (especially if the cancer involves the islet cells that make insulin and other hormones). These symptoms may also be caused by other, less serious health conditions. Anyone experiencing these symptoms should see a doctor.

Screening and Diagnosis

The doctor will ask about a patient’s symptoms and medical history, and a physical exam may be done. The doctor may order blood and urine tests and may also check for hidden blood in bowel movements.

Tests may include an upper GI (gastrointestinal) series, a series of X-rays of the upper digestive system taken after drinking a barium solution; a computed tomography (CT) scan, a type of X-ray that uses a computer to make pictures of structures inside the abdomen; a magnetic resonance imaging (MRI) scan, a test that uses magnetic waves to make pictures of structures inside the abdomen; and ultrasonography, a test that uses sound waves to find tumors. Other tests may include an endoscopic retrograde cholangiopancreatography (ERCP), a type of X-ray that shows the pancreatic ductal system after dye has been sent through a tube down the throat and into the pancreas; percutaneous transhepatic cholangiography (PTC), a type of X-ray test that shows blockages in the bile ducts of the liver; angiography, X-rays of blood vessels taken after an injection of dye that makes the blood vessels show up on the X-rays; and a biopsy, the removal of a sample of pancreatic tissue to test for cancer cells.

Treatment and Therapy

Once cancer of the pancreas is found, staging tests are performed. These tests help to find out if the cancer has spread and, if so, to what extent. Treatments for pancreatic cancer depend on the stage of the cancer.

Treatments include surgery to remove the cancerous tumor and nearby tissue. Nearby lymph nodes may also need to be removed. Surgery may also be performed to relieve symptoms of pancreatic cancer. Surgeries include the Whipple procedure, which is the removal of the head of the pancreas, part of the small intestine, and some of the tissues around it; a total pancreatectomy, which is the removal of the whole pancreas, part of the small intestine, part of the stomach, the bile duct, the gallbladder, the spleen, and most of the lymph nodes in the area; and a distal pancreatectomy, which is the removal of the body and tail of the pancreas.

Radiation therapy (radiotherapy) uses radiation to kill cancer cells and shrink tumors. In external radiation therapy, radiation is directed at the tumor from a source outside the body; in internal radiation therapy, radioactive materials are placed into the body in or near the cancer cells.

Chemotherapy is the use of drugs to kill cancer cells. It may be given in many forms, including pill, injection, and via a catheter. The drugs enter the bloodstream and travel through the body, killing mostly cancer cells. Some healthy cells are also killed.

Biological therapy is the use of medications or substances made by the body in order to increase or restore the body’s natural defenses against cancer. It is also called biologic response modifier (BRM) therapy.

Most times, pancreatic cancer is discovered at an advanced stage. Surgery may not be appropriate in this case. If surgery cannot be done, then chemotherapy and radiation are offered together to prolong survival.

Surgery would be appropriate in only 25 percent of patients with this disease in the early stage. In these cases, the patient would benefit from surgery. After surgery, follow-up chemotherapy and radiation therapy have been found to prolong survival in some cases.

Prevention and Outcomes

There are no guidelines for preventing this disease. Early-onset pancreatic cancer has been associated with five risk factors: cigarette smoking, diabetes, height, obesity, and non-O blood group. Individuals who think they are at risk for pancreatic cancer should talk to their doctors about ways to reduce their risk factors. Patients and doctors can work together to make an appropriate schedule for checkups.

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