# 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.