Adenomatous Polyposis Coli (APC) - Jewish Genetic Disease

Description
Familial Adenomatous Polyposis is an autosomal dominant genetically inherited condition that is caused by mutations in the Adenomatous Polyposis Coli tumor suppression gene. These mutations affect the cell’s ability to maintain normal function and growth. Proliferation of colon polyps results from the overgrowth of the cell, and often leads to colon cancer. In classical familial adenomatous polyposis the development of multiple noncancerous polyps may begin as early as teenage years. Unless the colon is removed the polyps will become malignant. The average age of individuals with FAP who develop colon cancer is 39.

The I1307K is one particular APC mutation that is present in 6% of the Ashkenazi Jewish population and 1-2% of Sephardi Jews. These individuals have a 10-20% risk of developing colorectal cancer which is slightly more than double then in the general population. They however do not develop the hundreds of polyps present in those with classic FAP.

Symptoms
Though polyps in the colon often do not cause any symptoms some of the following may be present:
   • Diarrhea
   • Change in bowel habits
   • Rectal Bleeding
   • Abdominal Pain

Incidence and Carriers
The reported incidence of familial adenomatous polyposis varies from 1 in 7,000 to 1 in 22,000 individuals in the general population.

The I1307K mutation in the Adenomatous Polyposis Coli gene, is found in 6% of Ashkenazi Jewish population and 1-2% of Sephardi Jewish population. Ten to twelve percent of Ashkenazi Jews who carry this mutation and have no family history develop colorectal cancer. However, 28% of Ashkenazi Jews who have colorectal cancer and a family history of the disease have been found to carry this mutation.

Treatment
It is crucial for people, who test positive for the APC I1307 gene mutation, to commit to a routine screening schedule for polyps and cancer. If these individuals do not already have polyps or colon cancer they should have a routine colonoscopy every two years staring at age 35 or five to ten years prior to the age colon cancer was identified in a one of the members of the family (whichever is younger).

It is highly recommended that individuals, who have family members who tested positive for the I1307K gene mutation, be screened for colon cancer and undergo genetic counseling.

Testing
Genetic testing for the I1307K gene mutation is recommended to any Jewish person of Ashkenazi descent who has personal or family history of colon polyps or colon cancer

Laboratories and Screening
The following laboratories offer genetic testing for APC with I1307K Mutation:
• United States
• Israel

UNITED STATES
Huntington Medical Research Institutes
Cancer Genetics Laboratory
Pasadena, CA
Phone: (626) 795-4343
Fax: (626) 795-5774
Email: eggerding@hmri.org
***Target Mutational Analysis Only

John Hopkins Pathology Molecular Diagnostic Laboratories
Barbara Kurgansky
(for genetic risk and oncology)
600 North Wolfe Street, Park SB202
Baltimore,Maryland 21287
Phone: (410) 614-1997 (8am-5pm EST)
Email: bkurgan@jhmi.edu
***Target Mutational Analysis Only

ISRAEL
GGA –Galil Genetic Analysis Ltd
P.O.B. 3664
Kazerin, Hatzafon, Israel 12900
Phone: (+972) 4-9007100
Fax: (+972) 4-9007111
Email: gga@gga.org.il

Pronto Diagnostic Ltd.
19A Habarzel Street
Ramat Hachayal
Tel Aviv, Israel 69710
Phone: (+972) 73-3126155
Fax: (+972) 73-2126144
Email: info@prontodiagnostics.com

Rabin Medical Center
Molecular Genetics
Petah Tikva, Israel
Director: Mordechai Shohat, MD
Genetic Counselor: Inbal Kedar, MSc
Phone: (+972) 39377659
Fax: (+972) 39377660
Email: inbalkd@clalit.org.il

Rambam Medical Center, Molecular Genetics Laboratory
PO Box 9602 Haifa 31096 Israel
Phone: (+972) 4-8542456
Prof. Ruth Gershoni -Baruch
Email: rgershoni@rambam.health.gov.il

Sheba Medical Center
The Danek Gertner Institute Human Genetics
Molecular diagnosis Laboratory
Tel Hashomer; Ramat Gan . 52621, Israel
Phone: (+972) 3-5303060
Web: http://www.eng.sheba.co.il/

Support Groups
Colon Cancer Alliance http://www.ccalliance.org/about/index.html

In the UK: Polyposis Registry at St Mark's Hospital, London: http://www.polyposisregistry.org.uk

IMPACC (Intestinal Multiple Polyposis and Colorectal Cancer)
Address: P.O. Box 11
Conyngham, Pennsylvania 18219
Phone: (570)788-1818 or (570) 788-3712
Fax: (570) 788-4046
Email: impacc@epix.net
Description: IMPACC is a support group for families with FAP and/or hereditary colon cancer.

Title: UOA (United Ostomy Association)
URL: http://uoa.org
Address: National Headquarters
19772 MacArthur Blvd., Suite 200
Irvine, California 92612-2405
Phone: (800) 826-0826
Email: info@uoa.org
Description: The UOA is a national volunteer-based organization. More than 500 chapters are made up of people with ostomies whose goal is to provide mutual aid, moral support, and education to those who have had colostomy or ileostomy surgery. Check the telephone directory for your local chapter.