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  • Test code: 01709
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
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Invitae Familial Adenomatous Polyposis Test

Test description

This test analyzes the APC gene. Pathogenic variants in this gene can cause APC-associated polyposis conditions, which include familial adenomatous polyposis (FAP), attenuated FAP (AFAP), and gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). These disorders are primarily associated with the development of numerous colon polyps and colon 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.

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Primary panel (1 gene)

Alternative tests to consider

APC can also be ordered as part of a broader panel to test for different types of hereditary cancer, including colorectal and pancreatic cancers. Depending on the individual’s clinical and family history, one of these broader panels may be appropriate. Any of these broader panels can be ordered at no additional charge.

  • Familial adenomatous polyposis (FAP)
  • Attenuated familial adenomatous polyposis (AFAP)
  • Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS)

Familial adenomatous polyposis (FAP) is a colorectal cancer predisposition syndrome characterized by the development of hundreds to thousands of precancerous (adenomatous) polyps, typically beginning in adolescence or early adulthood. Without a prophylactic colectomy, individuals with FAP have a lifetime risk of nearly 100% for developing colorectal cancer. AFAP has a later age of onset than classic FAP, presents with fewer adenomatous polyps (<100), and has an overall lower lifetime risk of developing cancer (approximately 70%).

GAPPS is characterized by fundic gland polyposis and an increased risk of gastric cancer (gastric adenocarcinoma). Polyps are often associated with low-grade and focally high-grade dysplasia. Unlike other pathogenic variants in APC, the risk of colorectal polyposis and cancer appears to be lower. GAPPS is caused by pathogenic variants in promoter 1B of the APC gene, which this test analyzes.

FAP was previously divided into subtypes including Turcot and Gardner syndromes. These subtypes were defined by the presence of certain extracolonic findings such as desmoid tumors, sebaceous cysts, osteomas, supernumerary teeth, and cancers of the duodenum, exocrine pancreas, thyroid (papillary adenocarcinoma), liver (hepatoblastomas), and central nervous system (medulloblastomas). It is now recognized that these subtypes are part of the clinical spectrum of APC-associated polyposis conditions.

FAP is a highly penetrant condition. If it is left untreated, affected individuals have a lifetime risk of nearly 100% of developing colorectal cancer. For AFAP, the lifetime risk for colorectal cancer is 70%. GAPPS-associated cancer risks are currently unknown. See the table below for FAP-associated cancer risks:

Cancer typeCancer risk
ColonUp to 100% (70% for attenuated FAP)
SarcomaUp to 25%
Duodenal4%-12%
Thyroid1%-2%
Brain1%-2%
Hepatoblastoma (up to age 5)1%-2%
GastricUp to 0.5%
PancreaticElevated

Analysis of the APC gene detects pathogenic variants in up to 90% of individuals with clinical FAP. The clinical sensitivity for GAPPS is currently uncertain.

APC-associated polyposis conditions are inherited in an autosomal dominant pattern. Most cases are inherited from a parent; however, up to 25% of cases are due to a spontaneous de novo mutation.

APC-associated polyposis conditions historically accounted for approximately 0.5% of all colorectal cancer, but this number is decreasing with increased awareness, early detection, and intervention. Collectively, the APC-associated polyposis conditions have a prevalence of approximately 2-3 in 100,000 individuals.

Clinical testing for FAP should be considered in individuals with:

  • 10 or more adenomatous colon polyps with or without a colorectal or other FAP-associated cancer
  • cribriform morular variant of papillary thyroid cancer
  • a desmoid tumor
  • hepatoblastoma diagnosed before the age of 5

Clinical testing for GAPPS should be considered in individuals with:

  • gastric polyps
  • fundic gland polyps
  • >100 polyps in the proximal stomach, or more than 30 polyps in a first-degree relative of an individual with GAPPS
  • relative with gastric polyps, fundic gland polyps or gastric adenocarcinoma

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  2. Bianchi, LK, et al. Fundic gland polyp dysplasia is common in familial adenomatous polyposis. Clin. Gastroenterol. Hepatol. 2008; 6(2):180-5. doi: 10.1016/j.cgh.2007.11.018. PMID: 18237868
  3. Biasco, G, et al. Risk of duodenal cancer in patients with familial adenomatous polyposis. Gut. 2004; 53(10):1547; author reply 1547. doi: 10.1136/gut.2003.027771. http://ncbi.nlm.nih.gov/pubmed/15361514 PMID: 15361514
  4. Bisgaard, ML, et al. Familial adenomatous polyposis (FAP): frequency, penetrance, and mutation rate. Hum. Mutat. 1994; 3(2):121-5. PMID: 8199592
  5. Burt, RW, et al. Genetic testing and phenotype in a large kindred with attenuated familial adenomatous polyposis. Gastroenterology. 2004; 127(2):444-51. PMID: 15300576
  6. Giardiello, FM, et al. Hepatoblastoma and APC gene mutation in familial adenomatous polyposis. Gut. 1996; 39(6):867-9. doi: 10.1136/gut.39.6.867. http://ncbi.nlm.nih.gov/pubmed/9038672 PMID: 9038672
  7. Giardiello, FM, et al. Increased risk of thyroid and pancreatic carcinoma in familial adenomatous polyposis. Gut. 1993; 34(10):1394-6. doi: 10.1136/gut.34.10.1394. PMID: 8244108
  8. Giardiello, FM, et al. The use and interpretation of commercial APC gene testing for familial adenomatous polyposis. N. Engl. J. Med. 1997; 336(12):823-7. doi: 10.1056/NEJM199703203361202. PMID: 9062090
  9. Groen, EJ, et al. Extra-intestinal manifestations of familial adenomatous polyposis. Ann. Surg. Oncol. 2008; 15(9):2439-50. doi: 10.1245/s10434-008-9981-3. PMID: 18612695
  10. Groves, CJ, et al. Duodenal cancer in patients with familial adenomatous polyposis (FAP): results of a 10 year prospective study. Gut. 2002; 50(5):636-41. doi: 10.1136/gut.50.5.636. http://ncbi.nlm.nih.gov/pubmed/11950808 PMID: 11950808
  11. Gurbuz, AK, et al. Desmoid tumours in familial adenomatous polyposis. Gut. 1994; 35(3):377-81. doi: 10.1016/0959-8049(94)90655-6. PMID: 8150351
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  13. Hamilton, SR, et al. The molecular basis of Turcot's syndrome. N. Engl. J. Med. 1995; 332(13):839-47. doi: 10.1056/NEJM199503303321302. http://ncbi.nlm.nih.gov/pubmed/7661930 PMID: 7661930
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  22. Li, J, et al. Point Mutations in Exon 1B of APC Reveal Gastric Adenocarcinoma and Proximal Polyposis of the Stomach as a Familial Adenomatous Polyposis Variant. Am. J. Hum. Genet. 2016; 98(5):830-42. PMID: 27087319
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  24. Lin, Y, et al. Novel APC promoter and exon 1B deletion and allelic silencing in three mutation-negative classic familial adenomatous polyposis families. Genome Med. 2015; 7(1):42. PMID: 25941542
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  32. Repak, R, et al. The first European family with gastric adenocarcinoma and proximal polyposis of the stomach: case report and review of the literature. Gastrointest. Endosc. 2016; 84(4):718-25. PMID: 27343414
  33. Robson, ME, et al. American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility. J. Clin. Oncol. 2010; 28(5):893-901. PMID: 20065170
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  35. Sieber, OM, et al. Disease severity and genetic pathways in attenuated familial adenomatous polyposis vary greatly but depend on the site of the germline mutation. Gut. 2006; 55(10):1440-8. PMID: 16461775
  36. Snow, AK, et al. APC promoter 1B deletion in seven American families with familial adenomatous polyposis. Clin. Genet. 2015; 88(4):360-5. PMID: 25243319
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Assay and technical information

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* NM_000038.5

APC: The 1B promoter region is covered by both sequencing and deletion/duplication analysis. The 1A promoter region is covered by deletion/duplication analysis.