The Invitae Hereditary Polyposis Panel analyzes the APC and MUTYH genes, which are associated with familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP). These conditions are associated with an increased risk of developing adenomatous polyps and colorectal cancer.
Genetic testing of this gene may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.
These genes can also be ordered individually or as part of broader multi-gene panels. Depending on the individual’s clinical and family history, a broader panel may be appropriate. Any of these broader panels can be ordered at no additional charge.
Colorectal cancer (CRC) is the third-most-common cancer diagnosis in the United States. Most cases are sporadic and not inherited; however, approximately 5%-10% of colorectal cancer is hereditary and due to an identifiable pathogenic variant.
Hereditary colorectal cancer syndromes that are covered by this test include familial adenomatous polyposis (FAP), attenuated familial adenomatous polyposis (AFAP), and MUTYH-associated polyposis (MAP). These disorders are associated with an increased lifetime risk of developing colorectal cancer.
Familial adenomatous polyposis (FAP) is a colorectal cancer syndrome characterized by the development of hundreds to thousands of precancerous (adenomatous) polyps, typically beginning in adolescence or early adulthood. Without a prophylactic colectomy, there can be up to a 100% lifetime risk of developing colon cancer.
Several clinical subtypes of FAP have been described. Gardner syndrome has the same disease progression and risk of colon cancer as classic FAP, but is also associated with the development of other extracolonic findings, both benign and malignant. These include desmoid tumors, sebaceous cysts, osteomas, supernumerary teeth, liver (hepatoblastomas) and central nervous system tumors (medulloblastomas), and cancers of the duodenum, exocrine pancreas, and thyroid (papillary adenocarcinoma). Turcot syndrome is a subtype of FAP that is characterized by numerous colon adenomas and medulloblastoma. Another subtype, attenuated familial adenomatous polyposis (AFAP), has a later age of onset and presents with fewer adenomatous polyps (<100). AFAP has an overall lower lifetime risk of developing colorectal cancer—approximately 70%.
MUTYH-associated polyposis (MAP) is a colorectal cancer predisposition syndrome characterized by the growth of tens to hundreds of adenomatous colorectal polyps. MAP generally has a less severe clinical presentation than FAP. Individuals with MAP have a 43%-100% lifetime risk of developing colorectal cancer. Occasionally, affected individuals will develop colon cancer in the absence of polyposis. MAP is also associated with an increased risk of developing upper gastrointestinal tract cancers, including duodenal adenomas and possibly other cancers.
Individuals affected with MAP have two pathogenic variants, one in each copy of their MUTYH genes. There is some evidence to suggest that individuals who have a single pathogenic variant in MUTYH may also be at slightly increased risk for colorectal cancer.
Individuals with a pathogenic variant in one of these genes have an increased risk of malignancy compared to the average person, but not everyone with such a variant will actually develoip cancer. Further, the same variant can present differently, even among family members. Because we cannot predict which cancers may develop, additional medical management strategies focused on cancer prevention and early detection may benefit most patients who are found to have a pathogenic variant. For gene-associated cancer risks, see the tables below.
|Cancer type||Cancer risk|
|Colon||Up to 100% (70% for attenuated FAP)|
|Sarcoma||Up to 25%|
|Hepatoblastoma (up to age 5)||1%-2%|
|Gastric||Up to 0.5%|
|Cancer type||Lifetime cancer risk|
FAP has autosomal dominant inheritance. Most cases of FAP are inherited; however, up to 25% of cases are due to a spontaneous de novo mutation.
MAP is autosomal recessive, though some literature suggests that individuals who carry a single pathogenic variant may have an increased risk for colorectal cancer.
Colorectal cancer occurs in approximately 1 in 22 individuals in the general population.
APC-associated polyposis conditions historically accounted for approximately 0.5% of all colon cancer, but this number is decreasing with greater awareness, early detection, and intervention. Collectively, the APC-associated polyposis conditions have a prevalence of approximately 2-3 in 100,000 individuals.
Approximately 1%-2% of individuals of northern European ancestry are carriers of a MUTYH variant. The prevalence of MAP in this population is estimated at 1 in 20,000 to 1 in 40,000. It is difficult to determine the prevalence of this condition in other ethnicities because the carrier frequency can vary significantly.
The Invitae Hereditary Polyposis Panel may be considered for individuals with a personal and/or family history of:
For management recommendations, please refer to:
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Genetic/Familial High-Risk Assessment: Colorectal 3.2017. ©National Comprehensive Cancer Network, Inc 2016. All rights reserved. Accessed November 16, 2017.
To view the most recent and complete version of the guideline, go online to NCCN.org.
National Comprehensive Cancer Network®, NCCN®, NCCN Guidelines®, and all other NCCN content are trademarks owned by the National Comprehensive Cancer Network, Inc.
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.
Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|
APC: The 1B promoter region is covered by both sequencing and deletion/duplication analysis. The 1A promoter region is covered by deletion/duplication analysis.