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

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