DESCRIPTION
There are currently two well-defined types of hereditary colorectal cancer. The types are familial adenomatous polyposis (FAP) and Lynch syndrome (formerly hereditary nonpolyposis colorectal cancer or HNPCC).
Clinical manifestations of FAP usually occur during adolescence, and are typically apparent by 10 years of age. If left untreated, all affected individuals will go on to develop colorectal cancer. Unlike other mutations in the APC gene, which result in an alteration in the protein length, the I1307K mutation is termed a missense mutation. It is hypothesized that the APC I1307K mutation itself does not cause colon cancer; rather this particular mutation appears to create a weak spot in the gene that makes it more susceptible to additional genetic changes that may in turn lead to colon cancer. FAP accounts for 1% of colorectal cancer and may also be associated with other inherited disorders such as Gardner’s syndrome or Peutz-Jeghers syndrome. FAP can be identified by the appearance of characteristic polyps.
Individuals with HNPCC (also known as Lynch syndrome) tend to have early onset colorectal cancer, right-sided tumors, and often multiple cancers. HNPCC is estimated to account for 3% to 5% of colorectal cancer and is often associated with increased risk of other cancers such as endometrial, ovarian, urinary tract, and biliary tract cancer. The lifetime risk of developing colorectal cancer in HNPCC is approximately 80%. The identification of HNPCC is based primarily on family history and related criteria (e.g., Amsterdam II criteria, Bethesda guidelines). HNPCC is associated with mutations in 1 of 5 different genes, located on chromosomes 2, 3 or 7. These genes are known as MLH1, MSH2, MSH6, PMS1 and PMS2. More than 95% of individuals with HNPCC have mutations in either hMLH1 or hMSH2. All of the genes are involved in DNA mismatch repair (MMR) mechanisms. In HNPCC, 1 MMR gene mutation is inherited; errors in microsatellite sequences follow somatic activation of the other MMR gene allele in precancerous and cancerous cells. Thus, detection of alterations in DNA microsatellite sequences (termed microsatellite instability or MSI) reflects a biological consequence of malignancy, rather than just an associated marker. The microsatellite instability test may be used for this detection. Absent or reduced protein expression may be a consequence of an MMR gene mutation. Immunohistochemistry (IHC) assays for the expression of MLH1 and MSH2 may be used to detect loss of expression of these genes and to focus HNPCC mutation testing efforts on a single gene.
POLICY
Genetic testing to determine the carrier status for susceptibility to colon cancer is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Pre- and post-genetic counseling is considered medically necessary as an adjunct to genetic testing.
MEDICAL APPROPRIATENESS
Genetic testing to determine the carrier status is considered medically appropriate if ANY ONE of the following criteria are met:
ANY ONE of the following criteria are met (revised Bethesda Guidelines):
Colorectal cancer diagnosed in an individual younger than 50 years of age
Presence of synchronous, metachronous colorectal, or other Lynch syndrome-associated tumors (i.e., endometrial, stomach, ovarian, pancreas, ureter and renal pelvis, biliary tract, brain tumors, sebaceous gland ademonas and keratoacanthomas, and carcinoma of the small bowel), regardless of age
Colorectal cancer with MSI-high pathologic associate features diagnosis in an individual younger than 60 years of age
Colorectal cancer or Lynch syndrome-associated tumor (i.e., endometrial, stomach, ovarian, pancreas, ureter and renal pelvis, biliary tract, brain tumors, sebaceous gland ademonas and keratoacanthomas, and carcinoma of the small bowel), diagnosed in at least one first-degree relative younger than 50 years
Colorectal cancer or Lynch syndrome-associated tumor (i.e., endometrial, stomach, ovarian, pancreas, ureter and renal pelvis, biliary tract, brain tumors, sebaceous gland ademonas and keratoacanthomas, and carcinoma of the small bowel), diagnosed at any age in two first-degree or second-degree relatives
Family history meeting ALL of the following criteria (revised Amsterdam criteria):
Three or more relatives with a Lynch syndrome-associated cancer (i.e., colorectal cancer, cancer of the endometrium, small bowel, ureter, or renal-pelvis.)
One of the three is a first-degree relative of the other two
Two or more successive generations affected
One relative diagnosed before 50 years of age
Familial adenomatous polyposis (FAP) is excluded
Tumors are verified by pathological examination
Greater than 10 adenomas in the same individual
Multiple gastrointestinal hamartomatous polyps or hyperplastic polyps meeting ANY ONE of the following criteria:
Two or more hamartomatous polyps of the small intestine with ANY ONE of the following:
Mucocutaneous hyperpigmentation of the mouth, lips, nose, eyes, genitalia, or fingers
Family history of Peutz-Jeghers Syndrome
Juvenile polyposis syndrome determined by ANY ONE of the following:
Three or more juvenile polyps of the colon
Multiple juvenile polyps throughout the gastrointestinal tract
Any number of juvenile polyps with a family history of juvenile polyposis syndrome
Five or more histologically diagnosed hyperplastic polyps proximal to the sigmoid colon with 2 greater than 10 mm in diameter
One hyperplastic polyposis occurring proximal to the sigmoid colon with at least one first-degree relative with hyperplastic polyposis
Greater than 20 hyperplastic polyposis distributed throughout the colon
Family history (first- or second-degree relative) of known hereditary syndrome associated with colorectal cancer, with or without known mutation
IMPORTANT REMINDER
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member’s health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
ADDITIONAL INFORMATION
At-risk individual refers to first degree relatives. However, in the case of a small family pedigree, some judgement must be allowed in some cases (i.e., in the case of a small family pedigree, when extended family members may need to be included in the testing strategy).
It is recommended that, when possible, initial genetic testing for FAP or Lynch syndrome is performed in an affected family member so that testing in unaffected family members can focus on the mutation found in the affected family member.
Laboratories that conduct genetic testing must comply with the provisions of the Clinical Laboratory Improvement Act (CLIA), which is administered by the Health Care Financing Administration (HCFA) and the Centers for Disease Control and Prevention (CDC).
Genetic counselors must be licensed, certified, or eligible for board certification in their profession, and must have specific training in cancer genetics. They must also be a member of a national genetics society or a national oncology society (NCI requirements).
SOURCES
American Cancer Society. (2011, March). Can colorectal polyps and cancer be found early? Retrieved March 15, 2011 from http://www.cancer.org/Cancer/ColonandRectumCancer/DetailedGuide/colorectal-cancer-detection.
American College of Gastroenterology. (2008, December). American College of Gastroenterology Guidelines for colorectal cancer screening 2008. Retrieved March 17, 2011 from http://www.acg.gi.org/physicians/pdfs/CCSJournalPublicationFebruary2009.pdf.
American Society of Clinical Onology. (2010, February). Policy statement update: Genetic and genomic testing for cancer susceptibility. Retrieved March 14, 2011 from http://www.jco.ascopubs.org/content/28/5/893.full.pdf.
BlueCross BlueShield Association. Medical Policy Reference Manual. (10:2009). Genetic testing for inherited susceptibility to colon cancer, including microsatellite instability testing (2.04.08). Retrieved January 26, 2010 from BlueWeb. (19 articles and/or guidelines reviewed)
Desai, T. K. & Barkel, D. (2008). Syndromic colon cancer: Lynch syndrome and familial adenomatous polyposis. Gastroenterology Clinics of North America (37), 47-72. (Level 5 evidence)
Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group. (2009). Recommendations from the EGAPP Working Group: genetic testing strategies in newly diagnosed individuals with colorectal cancer aimed at reducing morbidity and mortality from Lynch syndrome in relatives. Genetics in Medicine, 11 (1), 35-41.
Levin, B., Lieberman, D. A., McFarland, B., Smith, R. A., Brooks, D., Andrews, K. S., et al. (2008). Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: A joint guideline from the American Cancer Society, the U. S. Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. Retrieved March 15, 2011 from http://caonline.amcancersoc.org/cgi/reprint/58/3/130.pdf.
Mukherjee, A., McGarrity, T. J., Ruggiero, F., Koltun, W., McKenna, K., Poritz, L., et al. (2010). The revised Bethesda guidelines: extent of utilization in a university hospital medical center with a cancer genetics program. Hereditary Cancer in Clinical Practice, 8:9 (Level 2 evidence).
National Comprehensive Cancer Network. (2011). NCCN clinical practice guidelines in oncology™. Colorectal Cancer Screening (V.2.2011). Retrieved March 14, 2011 from http://www.nccn.org/professionals/physician_gls/pdf/colorectal_screening.pdf.
O’Dwyer, P. J., Eckhardt, S. G., Haller, D. G., Tepper, J., Ahnen, D., Hamilton, S., et al. (2007). Priorities in colorectal cancer research: Recommendations from the Gastrointestinal Scientific Leadership Council of the Coaltition of Cancer Cooperative Groups. American Journal of Clinical Oncology, 25 (16), 2313-2319.
U. S. National Institutes of Health. National Cancer Institute. (2011, February). Genetics of Colorectal Cancer (PDQ®) Health Professional Version. Retrieved March 14, 2011 from http://www.cancer.gov/cancertopics/pdq/genetics/colorectal/HealthProfessional/AllPages.
ORIGINAL EFFECTIVE DATE: 6/14/1999
MOST RECENT REVIEW DATE: 5/12/2011
ID_BT
Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.
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