Genetic counseling: Familial Adenomatous Polyposis

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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 multiple 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.

This material has been imported fom the wikibook "Genetic counseling"[ http://en.wikibooks.org/wiki/Genetic_counseling] under the GNU Free Documentation License.

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