According to the National Cancer Institute, each year, about 70,000 adolescents and young adults (AYAs)—those between the ages of 15 and39—are diagnosed with cancer.¹ Evidence suggests that some cancers found in AYAs may have unique genetic and biologic features. The findings of a recent study by researchers at Memorial Sloan Kettering Cancer Center (MSK) investigating the prevalence of germline susceptibility in young adults with cancer add to that evidence.

Zsofia K. Stadler, MD

Lead study author Zsofia K. Stadler, MD, a medical oncologist at MSK, and colleagues found that 21% of patients with early-onset cancer and 13% of patients with young-adult cancer had an inherited genetic mutation. The study’s findings support a role for genetic testing in young adults regardless of tumor type, according to the authors.² The study findings were presented during the 2020 American Association for Cancer (AACR) Virtual Annual Meeting II.

Study Methodology and Key Findings

The researchers performed germline analysis on 1,201 young adults between the ages of 18 and 39 with diverse solid tumors. They used a germline genetic testing protocol of MSK-IMPACT, which utilizes a next-generation sequencing panel consisting of up to 88 genes previously implicated in cancer predisposition, in their analysis. Based on Surveillance, Epidemiology, and End Results (SEER) Program data, the researchers divided the young adults into the following categories: early-onset cancer, defined as cancer wherein age 39 is at least 1 standard deviation (STD) below the mean age of diagnosis for that cancer type, which included 877 patients; and young-adult cancer, defined as cancer wherein age 39 is less than 1 standard below the mean age at cancer diagnosis, which included 324 patients.

The researchers found that among the patients with early-onset cancer, the most common cancers were colorectal, breast, kidney, pancreatic, and ovarian. Among those with young-adult cancer, the most common cancers were sarcoma, brain, testicular, and thyroid.

Germline prevalence of likely pathogenic or pathogenic variants was 21% in the early-onset patients vs 13% in young-adult patients (P = .002), with an enrichment of high- and moderate-penetrance pathogenic variants in the early-onset cohort (15% vs 10%; P = .01). Among those with early-onset cancers, the most commonly mutated genes were BRCA2, BRCA1, CHEK2, and ATM, with pancreatic, breast, and kidney cancers harboring the highest rates of germline pathogenic variants. In contrast, in the young-adult cohort, TP53 and SDHA mutations predominated. Among young-adult patients with sarcoma, the 18.1% mutation prevalence was similar to the prevalence in early-onset patients.

“Our study demonstrates that the prevalence of inherited cancer susceptibility syndromes in young adults with cancer is not uniform,” said Dr. Stadler, during a press briefing on her study. “We found a very high prevalence of germline mutations in young patients with cancer types that typically present at later ages, which we categorize as early-onset cancers. Indeed, 21% of these patients harbor the germline variance. On the other hand, in the remainder of young adult patients with cancer, the germline mutation prevalence was lower at 13%…. Our results suggest that among patients with early-onset cancers, the increased prevalence of germline mutations supports a role for genetic testing irrespective of tumor type.”

Additional Commentary

Elaine R. Mardis, PhD, FAACR

In a commentary following the press briefing, moderator of the briefing, Elaine R. Mardis, PhD, FAACR, Co-Executive Director of the Steve and Cindy Rasmussen Institute for Genomic Medicine at Nationwide Children’s Hospital, Columbus, Ohio, said: “Here the surprising finding is that the germline prevalence of these mutations is significantly higher than we had previously thought. About 21% of the early-onset patients, those patients developing tumor types more commonly diagnosed in older adults, have germline susceptibility, pathogenic or likely pathogenic variance. And 13% of the young adults developing sarcomas, brain, testicular, or thyroid cancers have germline pathogenic or likely pathogenic variance.” 

DISCLOSURE: Funding for the study was provided by the Precision, Interception, and Prevention Program; the Marie-Josée and Henry R. Kravis Center for Molecular Oncology; and the Robert and Kate Niehaus Center for Inherited Cancer Genomics, all at MSK. For full disclosures of the study authors, visit abstractsonline.com.

REFERENCES

1. National Cancer Institute: Adolescents and Young Adults With Cancer. Available at https://www.cancer.gov/types/aya. Accessed June 22, 2020.

2. Stadler ZK, Maio A, Padunan A, et al: Germline mutation prevalence in young adults with cancer. 2020 AACR Virtual Annual Meeting II. Abstract 1122/4.