Inherited cancer syndromes are genetic conditions that cause a predisposition to certain types of cancer. Specific cancer risks vary depending on the gene involved. Laboratory testing is used to determine whether an individual has inherited a familial predisposition to cancer and whether there is a risk of passing the condition to offspring. In some types of cancer, laboratory testing may also be used to screen for, monitor, and assess risk of tumors. This ARUP Consult topic provides an overview of germline genetic testing in hereditary cancer. Links to more information about other laboratory testing used in each type of cancer are provided throughout the text and in the Related Content section.
Topics from ARUP Consult
Indications for Testing
Genetic counseling should be offered to any individual who is considered to be at risk for hereditary cancer. Genetic testing may be recommended in some clinical circumstances and may inform medical management of the tested individual and any at-risk family members.
Initial testing to diagnose a hereditary cancer syndrome in a family may entail a multigene panel or single-gene testing, depending on the differential diagnosis. For family members of individuals with a known pathogenic variant, targeted testing for that familial variant is recommended.
Breast and Ovarian Cancer
Genetic testing for hereditary breast and ovarian cancer may involve single-gene testing for pathogenic variants (mutations) in genes such as BRCA1/2 or multigene panel testing for additional high- and moderate-penetrance genes associated with these cancers. Genes such as ATM, BRCA1/2, CHEK2, PALB2, and TP53 might be included in such a panel. For more information on genetic testing for hereditary breast cancer, see the Familial Risk (Hereditary) Genetic Testing section of the ARUP Consult Breast Cancer Biomarkers topic. For additional details on testing for hereditary ovarian cancer, see the ARUP Consult Ovarian Cancer topic.
The following Test Fact Sheets also provide information on genetic tests used in hereditary breast and ovarian cancer:
- BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer Syndrome
- Hereditary Breast and Ovarian Cancer Panel
Gastrointestinal cancers, including colorectal cancer, are a leading cause of cancer-related death. Lynch syndrome, which predisposes an individual to colorectal, gastric, and other cancers, is the most common type of hereditary gastrointestinal cancer syndrome. Other inherited syndromes, such as familial adenomatous polyposis, can also predispose affected individuals to colorectal cancers and polyps. Identification of hereditary gastrointestinal cancers affects screening recommendations for both the individual and family members. For more information, visit the ARUP Consult Colorectal Cancer and Lynch Syndrome topics and the Lynch Syndrome (HNPCC) Testing Algorithm.
The following Test Fact Sheets also provide information on genetic tests used in hereditary gastrointestinal cancer:
- Hereditary Gastrointestinal Cancer Panel, Including Lynch Syndrome
- Lynch Syndrome Panel, Sequencing and Deletion/Duplication
- Familial Adenomatous Polyposis and MUTYH-Associated Polyposis
Laboratory testing for MEN1 or RET variants is a critical component when assessing patients for multiple endocrine neoplasia syndromes. Testing for multiple endocrine neoplasia type 2 (MEN2) should also be considered if multiple individuals in a family have medullary thyroid cancer, although most thyroid cancers arise spontaneously. The ARUP Consult Multiple Endocrine Neoplasias topic provides an in-depth discussion of this and other relevant laboratory testing.
Other hereditary syndromes that confer a predisposition to endocrine tumors include Von Hippel-Lindau syndrome and hereditary paraganglioma/pheochromocytoma syndrome. See the following resources for more information:
- Pheochromocytoma - Paraganglioma ARUP Consult topic
- Paraganglioma - Pheochromocytoma Genetic Testing Algorithm
A subset of myelodysplastic syndromes, myeloid neoplasms, and other hematologic malignancies may arise due to heritable causes or a genetic predisposition. The Hereditary Myeloid Neoplasms Panel, Sequencing Test Fact Sheet discusses testing for germline variants in these conditions.
Germline genetic testing can provide useful information in prostate cancer, including information to help guide treatment in patients with metastatic disease and in those who may be able to participate in clinical trials. For more information about germline genetic testing in prostate cancer, refer to the ARUP Consult Prostate Cancer topic and the BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer Syndrome Test Fact Sheet.
Several genetic conditions are associated with an increased risk for different types of renal cancer, as well as other cancers or clinical conditions. See the Hereditary Renal Cancer Panel Test Fact Sheet for an overview of genetic testing in hereditary renal cancer.
The following Test Fact Sheet also provide information on tests used in related syndromes: Tuberous Sclerosis Complex
Endometrial (uterine) cancer may be associated with Lynch syndrome. See the ARUP Consult Lynch Syndrome topic for additional information. Benign uterine tumors (leiomyomas) may be observed in women with hereditary leiomyomatosis and renal cell cancer (HLRCC), a condition caused by pathogenic variants in the FH gene. The Hereditary Renal Cancer Panel Test Fact Sheet provides more details.
Other/Multiple Cancer Types
When a family history is suspicious for multiple hereditary cancer syndromes, genetic testing with a multigene panel may be the most efficient and cost-effective way to establish a diagnosis. The Hereditary Cancer Panel Test Fact Sheet includes additional information.
Syndromic Cancer Predisposition
Several hereditary syndromes are associated with a predisposition to cancer or benign tumors, among other distinctive features. These syndromes include Cowden syndrome/PTEN hamartoma tumor syndrome, neurofibromatosis type 1, Peutz-Jeghers syndrome, and tuberous sclerosis complex. Genetic testing may be useful in establishing the diagnosis. For more information, see the Tuberous Sclerosis Complex Test Fact Sheet.
Additional Content from ARUP Laboratories
Topics from ARUP Consult
Testing Algorithms from ARUP Consult
Test Fact Sheets from ARUP Consult
Hampel H, Bennett RL, Buchanan A, et al. A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. Genet Med. 2015;17(1):70-87. Reaffirmed with Addendum: Genet Med. 2019;21(12):2844.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: genetic/familial high-risk assessment—breast and ovarian. Version 1.2020. [Accessed: Aug 2020]
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: genetic/familial high-risk assessment—colorectal. Version 1.2020. [Updated: Jul 2020; Accessed: Feb 2021]
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Prostate cancer. Version 2.2021. [Updated: Feb 2021; Accessed: Aug 2021]