Genetic Testing for Cancer Susceptibility

Abstract

Approximately 10% of patients diagnosed with cancer have a germline variant in a gene that increases susceptibility to cancer. 1 The most common examples include germline pathogenic variants (mutations) in BRCA1 and BRCA2, which are associated with an increased risk of breast, ovarian, pancreatic, and prostate cancer, and germline pathogenic variants in MLH1, MSH2, MSH6, and PMS2 (Lynch syndrome), which are associated with increased risk of colorectal cancer, endometrial cancer, and other cancer types.More than 100 genes that increase susceptibility to cancer (with varied levels of penetrance and association with cancer susceptibility) have been described. 2 The prevalence of these germline genetic variants varies by cancer type, ranging from 4% to 6% in patients with lung cancer, esophageal cancer, and head and neck cancer to 30% for male patients with breast cancer. 3 In patients diagnosed with cancer, testing for gene variants associated with increased cancer susceptibility is important for at least 2 reasons. First, testing informs the most optimal treatment for a patient with cancer. Second, testing helps identify relatives who may have inherited genes that increase their cancer susceptibility. Identifying these genes could improve outcomes by increasing cancer screening and riskreducing measures such as preventive surgery. With the advent of next-generation sequencing technologies, genetic testing for cancer risk has shifted from sequential, singlegene testing to multiple-panel genetic testing using blood or saliva. These tests require only 2 to 4 weeks for results and are performed by several large commercial laboratories.For patients diagnosed with cancer for whom practice guidelines recommend genetic susceptibility testing, multiplepanel genetic testing is covered by most health insurance entities. Practice guidelines now recommend testing for inherited cancer susceptibility genes for all patients with ovarian, male breast, and pancreatic cancer. 4 For other cancer types, including female breast, prostate, and colorectal, the criteria for testing have expanded, with more practice guidelines now advocating for genetic susceptibility testing for all patients or increasing subsets of patients. [4][5][6] Genetic testing for inherited cancer syndromes has become an integral component of cancer care because it directly affects management and therapy. 1,7 In 2014, the first poly (adenosine diphosphate-ribose) polymerase inhibitor was approved by the US Food and Drug Administration for BRCAassociated ovarian cancer, and more recently approval has been expanded to include treatment for BRCA-associated breast cancer, pancreatic cancer, and prostate cancer. 8 At the time of Related articleOpinion EDITORIAL