Hereditary Cancer Genetic Testing - Germline Testing for Inherited Cancer Syndromes

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.

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Topics from ARUP Consult

Breast Cancer Biomarkers

Lynch Syndrome - Hereditary Nonpolyposis Colorectal Cancer

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.

Laboratory Testing

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:

Gastrointestinal Cancer

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:

Endocrine Tumors

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:

Hematologic Malignancies

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. The Li-Fraumeni Syndrome Test Fact Sheet includes additional information.

Prostate Cancer

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.

Renal Cancer

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 Sheets also provide information on tests used in related syndromes:

Endometrial Cancer

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 following Test Fact Sheets:

Additional Content from ARUP Laboratories

Topics from ARUP Consult

Breast Cancer Biomarkers

Colorectal Cancer

Lynch Syndrome - Hereditary Nonpolyposis Colorectal Cancer

Multiple Endocrine Neoplasias - MEN 

Ovarian Cancer

Pheochromocytoma - Paraganglioma

Prostate Cancer - PSA

Testing Algorithms from ARUP Consult

Lynch Syndrome (HNPCC) Testing Algorithm

Paraganglioma - Pheochromocytoma Genetic Testing Algorithm

Test Fact Sheets from ARUP Consult

BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer Syndrome

Familial Adenomatous Polyposis and MUTYH-Associated Polyposis

Hereditary Breast and Ovarian Cancer Panel

Hereditary Cancer Panel

Hereditary Gastrointestinal Cancer Panel, Including Lynch Syndrome

Hereditary Myeloid Neoplasms Panel, Sequencing

Hereditary Renal Cancer Panel

Peutz-Jeghers Syndrome

Tuberous Sclerosis Complex

Von Hippel-Lindau Syndrome

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