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.