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Prevalence of Germline Mutations Surprisingly High in Young Adults with Early-Onset Cancer

October 2020, Vol 11, No 5

Patients with “early-onset cancer”—that is, cancers that typically do not occur in younger adults (aged 18-39)—had a significantly higher rate of germline mutations than patients with the “young adult cancers” that are typically seen in this age-group (21% vs 13%, respectively; P = .002), according to results of a new study. The results were presented at the 2020 AACR virtual annual meeting and were highlighted at a meeting press cast.

In this study, early-onset cancers were defined as cancers that are not typically seen in younger patients; young adult cancers were defined as those likely to occur at younger ages.

Early-onset cancers—such as breast, colon, pancreatic, kidney, prostate, and ovarian—are rarely seen in young adults. Cancers that are often seen in young adults include brain, testicular, and sarcoma.

“Although they only represent about 4% of all cancers, young adults with cancer, defined as those diagnosed with cancer between the ages of 18 and 39, face unique challenges,” stated lead investigator Zsofia K. Stadler, MD, Medical Oncologist, Clinical Genetics Service, Memorial Sloan Kettering Cancer Center, New York City.

“Identifying whether a young patient’s cancer occurred in the setting of an inherited cancer predisposition syndrome is important, as it can result in a substantial change in clinical management, such as increased cancer surveillance aimed at early detection, and risk-reducing surgery to prevent new cancers, and may even have reproductive implications for young families,” Dr Stadler added.

“These results suggest that that there is a role for genetic testing in young adults with early-onset cancer irrespective of tumor type,” she emphasized.

Germline Mutations in Young Adults with Cancer

The study included 1201 young adults diagnosed with cancer between 2015 and 2019 at Memorial Sloan Kettering Cancer Center. The presence of germline mutations was assessed using the MSK-IMPACT next-generation sequencing assay that includes a panel of 88 genes known to be associated with susceptibility to cancer. The investigators analyzed DNA from blood samples of these patients for this study.

The SEER (Surveillance, Epidemiology, and End Results) registry data were used to identify 977 patients with early-onset cancers, as defined in this study.

The analysis showed that the most common early-onset cancers among these patients were colorectal (20%), breast (39%), kidney (6%), pancreatic (6%), and ovarian (6%). In addition, young adult cancers were diagnosed in 324 patients; of these, the most common were sarcoma (36%), brain (23%), testicular (17%), and thyroid (9%) cancers.

Among the early-onset breast, kidney, or pancreatic cancers, the most common germline mutations were BRCA1 or BRCA2 (4.9%), ATM (1.6%), CHEK2 (1.7%), and in genes associated with Lynch syndrome (2.2%). Germline TP53 mutations (2.2%) and SDHA/B (1.9%) were the most common in patients with young adult cancers.

Clinical Implications

“The findings are surprising. The prevalence of these germline mutations is significantly higher [in young adults] than previously thought: 21% of early-onset patients and 13% of patients with young adult cancer had germline pathogenic mutations, which has implications for genetic testing, surveillance, and counseling,” stated AACR Past President Elaine R. Mardis, PhD, FAACR, Co-Executive Director, Institute for Genomic Medicine, Nationwide Children’s Hospital, Columbus, OH, speaking at a premeeting press cast.

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