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.