# 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.