September 2023 | George M. Pikler, M.D., Ph.D., FACP

Genetic Testing for Cancer Susceptibility

Genes consist of linear sequences of four DNA nucleotides, or bases. In humans, every cell with a nucleus contains a copy of the entire genome—more than 3 billion DNA base pairs. Sequencing, is figuring out the order of DNA bases in a genome and seeing whether any letters are out of order, called a mutation, or variant. Most variants are harmless, but some can put people at higher risk of developing cancer and other diseases. Next generation sequencing (NGS) can scan many millions of base pairs—or the entire genome—for mutations at once. These sequence fragments are then checked against a reference genome to look for mutations. NGS multiple-panel genetic testing requires only 2 to 4 weeks for results and is performed by several large commercial laboratories. Testing is covered by most health insurance entities.

Approximately 10% of patients diagnosed with cancer have a germline variant in a gene that increases susceptibility to cancer. The most common examples include germline pathogenic mutations in BRCA1 and BRCA2, which are associated with an increased risk of breast, ovarian, pancreatic, and prostate cancer, and germline pathogenic mutations in MLH1, MSH2, MSH6, and PMS2 (Lynch syndrome), which are associated with increased risk of colorectal cancer, endometrial cancer, and other cancer types.

In patients diagnosed with cancer, testing for gene mutations associated with increased cancer susceptibility is important for at least 2 reasons. First, testing informs us which treatments may be most effective for that patient. Second, such testing may also help identify people whose family members should be offered testing for potential cancer-causing gene changes.

Clinicians must be familiar with practice guidelines indicating when cancer susceptibility genetic testing is indicated. They should recommend testing to their patients and provide them with the information necessary to make informed decisions about whether to undergo testing. Patients must have access to clear, reliable, and convenient sources of information to inform their decision to undergo testing and understand and manage test results. An individual visit with a genetic counselor should not be a prerequisite to testing.

JAMA.2023; 330 (1): 30-32

Erica Cross, PA


Erica is a board certified Physician Assistant. She obtained her Master’s degree in Physician Assistant studies from Our Lady of the Lake College in Baton Rouge, LA. She began practicing in 2011 and has worked clinically in Orthopedics and Dermatology. The majority of her career has been spent in a Dermatology practice where she assisted in Mohs surgery, treating various types of skin cancer. She also teaches in the medical simulation department at the University of South Alabama and enjoys every aspect of medical education.