Handbook of Genetic Counseling/Pancreatic Cancer

Pancreatic Cancer

Pancreatic Cancer

• Incidence is more than 29,000 new cases/year in US
  • Fifth leading cause of cancer death
  • 4.1% five-year survival rate is lowest of all cancers
  • About 9-10% of pancreatic cancer is familial
• Pancreas is a gland located in the abdomen between the stomach and the spine
  • Responsible for producing insulin, glucagon, and other hormones
  • Releases digestive juices through series of ducts leading to common bile duct
• Risk factors for pancreatic cancer
  • Smoking - increases risk 2-3 times
  • Age - most cancers diagnosed between 60 and 80 years
  • Diabetes
  • Chronic pancreatitis
    • Long-term inflammation of the pancreas
    • Especially inherited form of the condition
  • Family history
    • Risk increases by 4.7% if first degree relative has been diagnosed
    • Increases by 7.3% if diagnosis was made before age 60
    • Increases by 12.3% if multiple primary cancers in family
  • Males and African-Americans may be at increased risk
  • Diets high in fat may increase risk

Diagnosis and Surveillance Options

• Possible symptoms
  • Pain in upper abdomen or upper back
  • Yellowing of skin and eyes, dark urine due to jaundice
  • Weakness
  • Loss of appetite
  • Nausea and vomiting
  • Weight loss
• Physical exam
  • Look for signs of jaundice or changes in area near pancreas
  • Check for ascites (build-up of fluid in abdomen)
• Lab tests
  • Blood, urine, and stool samples
  • Check for bilirubin that may be high if tumor blocking common bile duct prevents its passage
• CT Scan
  • Produces detailed picture of abdomen
  • Can provide information about nature and location of tumors, resectability
• Ultrasonography
  • Transabdominal ultrasound
  • Endoscopic ultrasound (EUS)
    • Pass thin, illuminated optic instrument down mouth into stomach
    • Ultrasound device at tip of endoscope takes images of pancreas and surrounding areas
• Endoscopic Retrograde Cholangiopancreatography (ERCP)
  • Pass endoscope through mouth and stomach into first part of small intestine
  • Inject dye through catheter into ducts
  • Take X-rays to determine if ducts are narrowed or blocked by tumor
• Percutaneous Transhepatic Cholangiography (PTC)
  • Dye injected through needle inserted through skin into liver
  • Dye moves freely through bile ducts unless blocked
  • X-rays can show if dye has moved through ducts
• Biopsy
  • Fine-needle aspiration
  • During EUS or ERCP
  • Open abdomen during operation
• Laparoscopy
  • Uses several small incisions and TV camera to visualize organs in abdomen
  • Usually only used if CT scan shows evidence of metastases

Treatment

• Pancreatic cancer is currently difficult to treat so participation in clinical trials is often recommended
• Surgery
  • May be used alone or in combination with radiation or chemotherapy
  • Whipple procedure
    • If tumor is in head of pancreas
    • Remove head and part of small intestine, bile duct, and stomach
  • Distal pancreatectomy
    • Surgeon removes body and tail of pancreas
    • May also remove the spleen
  • Total pancreatectomy
    • Remove entire pancreas
    • Also remove part of small intestine and stomach, and all of common bile duct, gallbladder, spleen, and nearby lymph nodes
  • Create bypass or insert stent if tumor is blocking common bile duct or duodenum
    • Relives jaundice and pain resulting from blockage
    • Done if cancer cannot be completely removed surgically
  • Side effects of removal of all or part of pancreas
    • Diet control and medication may help with food digestion
    • Diarrhea, pain, cramping, and feelings of fullness are common
• Radiation therapy and chemotherapy often used to destroy cancer cells

Genetic Conditions Associated with Pancreatic Cancer

• Familial Atypical Multiple Mole Melanoma (FAMMM)
  • Due to mutations in p16 tumor suppressor gene
  • TP16 (CKDN2) located at 9p21
  • Affected individuals develop multiple nevi, atypical nevi, melanomas, and pancreatic cancer
• Peutz-Jeghers Syndrome
  • Due to mutations in LKB1 (STK11) gene at 19p13.3
  • Causes multiple hamartomaous polyps of GI tract and pigmented macules on lips, buccal mucosa, and digits
  • Increases risk to develop cancers
    • In women: breast, pancreas, uterus, and ovary
    • In men: colon, pancreas, lung, or testes
• Hereditary Breast-Ovarian Cancer Syndrome
  • Due to mutations in BRCA2 tumor suppressor gene at 13q12
  • Most common inherited predisposition to pancreatic cancer identified to date
  • Mutations in BRCA2 have been identified in individuals with no family history of breast or ovarian cancer
  • Estimated that carriers of 6174delT have 10-fold increased risk of developing pancreatic cancer
  • Increases risk for breast, ovarian, prostate, and colon cancers also
• HNPCC
  • Due to mutations in mismatch repair genes, including MSH2 and MLH1
  • Microsatellite instability has been identified in ~4% of pancreatic cancers
  • Should be considered in patients with family history of colon cancer
  • Increases risk for colon/rectum, endometrium, ovarian, urinary tract, stomach, and small intestine also
• MEN1
  • Due to mutations in menin tumor suppressor gene at 11q13
  • Associated specifically with insulinomas (10%) or gastrinomas (40%)
  • Can cause tumors on parathyroid and pituitary glands also
• Hereditary Pancreatitis
  • Due to mutations in cationic trypsinogen gene on 7q35
  • Block inactivation of trypsin, resulting in autodigestion of pancrease
  • Increase in pancreatic cancer may be secondary to chronic injury and repair
  • Clinical testing available through University of Pittsburgh
  • Penetrance of mutations is only 80%

Psychosocial Issues

• Worry about the future - caring for themselves, family, etc.
• Financial concerns
• Concerns about treatments and side effects
• Concern about necessity of frequent hospital visits, home care, etc.
• Feelings of guilt, anxiety, fear surrounding potential diagnosis of hereditary syndrome

Resources

• The National Familial Pancreas Tumor Registry

Dr. Ralph H. Hruban, Director

Baltimore, MD 21231-2410

Phone: (410) 955-9132

• Hereditary Pancreatitis Registry

Dr. Whitcomb or Dr. Lowenfels

The Midwest Multicenter Pancreatic Study Group

Phone: 888-PITT-DNA

• National Cancer Institute

Phone: 1-800-4-CANCER

http://cancer.gov

References

• Hruban RH, et al. "Familial Pancreatic Cancer." Annals of Oncology (1999) 10:S69-S73.
• "Pancreatic Cancer." Cancer Research UK. www.cancerresearchuk.org/aboutcancer
• Schenk M, et al. "Familial Risk of Pancreatic Cancer." Journal of the National Cancer Institute (2001) 93:640-644.
• "What you Need to Know About Cancer of the Pancreas. National Cancer Institute. www.nci.nih.gov/cancer

Notes

The information in this outline was last updated in June 2002.