Handbook of Genetic Counseling/Familial Adenomatous Polyposis

Familial Adenomatous Polyposis

Contracting

• Introductions
• Assess main concerns of patient
  • How did the referral to the Hereditary Cancer Program come about?
  • What do they hope to gain from the session?
• Assess knowledge of diagnosis
  • What do they already know about FAP?
  • What do they already know about hereditary cancer?
• Overview of today's agenda
  • Restate patient's concerns
  • Medical history, family history, genetics of hereditary cancer, inheritance pattern and recurrence risks, testing options and limitations

Review Medical and Family History

• Medical History
  • Any major health concerns?
  • Surgeries or hospitalizations?
  • Colon cancer screening?
• Family History
  • Other individuals with any type of cancer?
  • Focus on colorectal cancers, pancreatic cancer, thyroid cancer, brain cancer, as well as desmoid tumor cysts in the mandible
  • Screening practices of other family members?
  • Family thoughts about the cause of cancer?
  • Family experiences with cancer?

General Cancer Information

• All cancer is caused by a mixture of genes and environment
  • All cancer is genetic, but not all cancer is hereditary
  • Most cancers (90-95%) are sporadic
• Cancer Genetics
  • cells in our bodies are constantly growing and dividing
  • certain genes control/regulate cell growth
  • a change in these genes will result in a cell that grows out of control = cancer
    • the changes occur due to damage to the genetic material
    • DNA, genes, chromosomes
    • DNA contains the instructions for making proteins, which determine what cells do and regulate how we develop
    • the DNA must be copied each time a cell divides
    • sometimes a copying mistake, a typo, can occur
  • Hereditary forms of cancer involve a person inheriting one non-working copy of a gene
    • one step closer to developing cancer than a person with two working copies (therefore it is called an inherited predisposition)
    • features of hereditary cancer include:
      • earlier than expected age of onset
      • multiple generations affected
      • bilateral or multiple primary cancers
      • siblings affected

General Colorectal Cancer Information

• Statistics
  • third most common form of cancer
  • most colorectal cancers are sporadic
  • 6% (1/16) lifetime risk for colon cancer in the general population
  • most individuals diagnosed over the age of 50
    • average age of diagnosis is 67
  • risk factors include aging, diet, previous history of adenoma, colorectal cancer, or inflammatory bowel disease
  • about 5% of colon cancer is due to a hereditary predisposition
    • HNPCC (4%) and FAP (1%) are the two known forms
    • more likely to occur before the age of 50

FAP-specific information

• Clinical Characteristics
  • hundreds to thousands of adenomatous polyps in the colon and rectum at an early age
    • 90% of carriers will have polyps by the age of 20
    • virtually all carriers will have polyposis by the age of 35
    • malignancy will occur in virtually 100% of carriers by the age of 40-50
  • Classic FAP diagnosis requires a minimum of 100 polyps
  • Attenuated FAP generally has polyps developing at a later age and occurring proximally (though they may be found throughout the colon and rectum)
  • Gardner Syndrome (a phenotypic variant of FAP) is characterized by polyposis plus soft tissue tumors of the skin (epidermal cysts), osteomas, desmoid tumors, and supernumerary teeth
  • Colon cancer (average age of onset = 39 in FAP patients) is virtually inevitable if the colon is not removed prophylactically
• Genetics
  • due to mutations in the adenomatous polyposis coli (APC) gene
    • on chromosome 5q
    • autosomal dominant inheritance
    • a tumor suppressor gene
    • both alleles must be mutated for function to be lost
    • more than 700 mutations have been reported
    • most lead to truncation of the APC gene
    • most families have separate and distinct mutations
    • de novo mutations account for about 30% of FAP cases
    • mutations in the germ cell of a parent
• Screening and Management
  • annual flexible sigmoidoscopy or colonoscopy beginning at age 10-12
    • if polyps are found, they should be removed and a colectomy considered
  • routine upper GI endoscopy
  • if no polyps found by the age of 25, reduce screening frequency to once every two years until age 35, then every three years until age 50, then every 3-5 years after age 50
  • even if a colectomy is performed, life-long surveillance is required due to the association with extracolonic primary malignancies
  • the effectiveness of chemoprevention is not well established
    • the possibility of NSAID's are currently being evaluated in trials
• Associated Risks
  • primary adenomas and carcinomas of the duodenum
  • desmoid tumors (in 10% of FAP patients)
  • osteomas
  • thyroid carcinoma
  • brain tumors
  • hepatoblastoma
  • hepatopancreatic tumors
  • gastric fundic gland polyps
  • CHRPE (congenital hypertrophy of the retinal pigment epithelium)
• Risk Assessment
  • autosomal dominant inheritance (50% chance of inheriting it from an affected parent)
  • 30% are de novo mutations
  • penetrance is virtually 100% by the age of 40

Genetic Testing for FAP

• Two indications:
  • testing an individual who has a clinical diagnosis of FAP
  • testing an individual who is a relative of an established mutation carrier
    • testing an unaffected family member in the absence of an established mutation has a significant risk of a false negative result
    • since each family tends to have a unique mutation
• Protein Truncation Assay
  • the most common commercial test
  • able to identify most classical FAP mutations
  • once a mutation is identified, PTA is virtually 100% accurate in classifying carriers
• Denaturing Gradient Gel Electrophoresis (DGGE)
  • an alternative method that may be informative when PTA is not
  • involves direct sequencing of a region in which truncation is identified in an affected family member
• Gene Sequencing
  • maybe used when no other tests are informative
  • uses linkage analysis or flanking polymorphic genetic markers
  • requires a firm diagnosis of FAP in multiple family members
    • is therefore useless in the 30% of cases which are de novo

Resources

• American Cancer Society

800-227-2345

www.cancer.org

• CancerCare

800-813-4673

www.cancercare.org

References

• www.geneclinics.org
• www.cancer.org
• FAP background and screening macros (B.C. Hereditary Cancer Program)
• Module 6: "Hereditary Colorectal Cancer Syndromes" p 43-55
• "Hereditary Colorectal Cancer: A Guide for Patients and Their Families" by The Steve Atanas Stavro Familial Gastrointestinal Cancer Registry (Mount Sinai Hospital, Toronto, Canada)

FAP resources

• Colon Cancer Alliance

175 Ninth Avenue

New York, NY 10011

Phone: 212-627-7451; toll-free helpline 1-877-422-2030

Fax: 425-940-6147

Email: kelly@ccalliance.org

www.ccalliance.org

• Colorectal Cancer Network

PO Box 182

Kensington, MD 20895-0182

Phone: 301-879-1500

Fax: 301-942-7145

Email: semicolonclub@yahoo.com

www.colorectal-cancer.net

• Genetics of Colorectal Cancer (PDQ)

A service of the National Cancer Institute

www.cancer.gov/cancer_information

• Hereditary Colon Cancer Association (HCCA)

3601 N 4th Ave, Suite 201

Sioux Falls, SD 57104

Phone: 800-264-6783; 605-373-2067

Fax: 605-336-6699

Email: hcca@dtnet.com

www.hereditarycc.org

• IMPACC (Intestinal Multiple Polyposis and Colorectal Cancer)

PO Box 11

Conyngham, PA 18219

Email: impacc@epix.net

• American Cancer Society

1599 Clifton Rd NE

Atlanta, GA 30329

Phone: 800-227-2345

www.cancer.org/index.html

• Collaborative Group of the Americas for Inherited Colorectal Cancer

www.fascrs.org/ascrs-cancer-reg.html

Notes

The information in this outline was last updated in 2002.