Hereditary Cancer Spotlight: Importance of Germline Testing
Hereditary Cancer Spotlight
Importance of Germline Testing
Approximately 10% of adult cancers result from a pathogenic variant in DNA that contributes to hereditary cancer. These variants can be detected by germline testing. Unfortunately, germline testing is severely under-utilized. The actual rate of genetic testing ordered is only 6.8% (Allison W. Kurian, JAMA, 2023), which serves as a disadvantage for cancer patient care, potentially contributing to increased morbidity and mortality.
Germline cancer testing identifies inherited gene changes in DNA that are typically present in every cell of the body and can be passed from a parent to a child. This is different from somatic testing which looks for changes that occur in a specific tumor tissue or blood cells after birth. Performing germline testing can identify inherited variants present at birth that cause increased cancer risks; leading to personalized or more frequent cancer surveillance; specific treatment options for germline variants; and the opportunity for relatives to undergo preventative screening and risk-reducing strategies. This testing can result in earlier detection of cancers and guide current therapeutic decisions by revealing which treatments may be effective for an individual’s specific genetic profile. Additionally, germline testing should be distinguished from biomarker testing, which looks for somatic variations that are not inherited but are acquired through different biological methods.
The risk and presentation of hereditary cancers vary by sex, age, race, family history and ethnicity. Moreover, different types of cancers have different inherited risks and prevalence in the population. Some of the most common hereditary cancer types include breast, ovarian, colon, endometrial, pancreatic, prostate, gastrointestinal, and lung. Therefore, implementing early detection with germline testing can help better define the implications of a specific cancer and may be able to lower the cancer mortality rates based on these demographics.
Challenges in germline cancer testing include: when to consider testing, which panel to use, and how to interpret the results. Most third-party labs that perform germline testing offer genetic counseling and guidance to providers and patients to better assist in the appropriate test and interpretation of results.
In general, genetic testing for hereditary cancer syndromes should be considered in the following cases:
- Having a family member with a known inherited pathogenic genetic change that increases cancer risk
- Cancer diagnoses under the age of 50
- Several different types of cancer diagnosed in the same individual
- Multiple family members diagnosed with cancer with the following patterns:
- First-degree relatives (mother, father, siblings) with the same type of cancer
- Family members with breast or ovarian cancer
- Family members with colon or endometrial cancer
- Bilateral cancer in both organs such as kidneys or breasts
- Rare types of cancer (for example, male breast cancer)
Additional information on germline genetic testing can be found at:
The FCS Geneticists are available for clinical support: Dr. Jennifer Gass, Dr. Katy Phelan, Dr. Jeanine Ruggeri
References
- Kurian AW, Abrahamse P, Furgal A, et al. Germline Genetic Testing After Cancer Diagnosis. JAMA. 2023;330(1):43–51. doi:10.1001/jama.2023.9526
- Nadine Tung et al. Selection of Germline Genetic Testing Panels in Patients with Cancer: ASCO Guideline. J Clin Oncol42, 2599-2615(2024). DOI:1200/JCO.24.00662
- Link to NCI fact sheet https://www.cancer.gov/about-cancer/causes-prevention/genetics/genetic-testing-fact-sheet
