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Young Adults With Cancer May Benefit From Germline Genetic Testing


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According to the National Cancer Institute, each year, about 70,000 adolescents and young adults (AYA)—those between the ages of 15 and 39—are diagnosed with cancer. Evidence suggests that some cancers found in AYA patients may have unique genetic and biologic features.

Zsofia K. Stadler, MD

Zsofia K. Stadler, MD

A study that investigated the prevalence of germline susceptibility in patients with cancer between the ages of 18 and 39 found that 21% of the patients with “early-onset” cancer and 13% of those with “young adult” cancer had an inherited genetic mutation. The study by Zsofia K. Stadler, MD, and colleagues is being presented during the American Association for Cancer Research Virtual Annual Meeting II (Abstract 1122).

Study Methodology

The researchers performed germline analysis on 1,201 patients aged 18 to 39 years with a variety of solid tumors. They used a germline genetic testing protocol of MSK-IMPACT in their analysis, which utilizes a next-generation sequencing panel consisting of up to 88 genes previously implicated in cancer predisposition.

Based on Surveillance, Epidemiology, and End Results Program data, the researchers divided the patients into categories, including those with early-onset cancer (877 patients) and those with young adult cancer (324 patients). Early-onset cancer was defined as cancer wherein age 39 is > 1 standard deviation below the mean age of diagnosis for that cancer type, and young adult cancer was defined as cancer wherein age 39 is < 1 standard deviation below the mean age at cancer diagnosis. 

Study Findings

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

KEY POINTS

  • 21% of patients with early-onset cancer and 13% of patients with young adult cancer had an inherited genetic mutation.
  • Among patients with early-onset cancers, the highest rates of genetic mutations were found in those with cancer in the pancreas, breast, or kidney, with the most frequent mutations in the BRCA1, BRCA2, ATM, CHEK2 genes, and the Lynch syndrome-associated genes. Among patients with young-adult cancers, germline TP53 mutations were more common, which is consistent with Li-Fraumeni syndrome.
  • Among patients with early-onset cancers, the increased prevalence of germline mutations support a role for genetic testing regardless of tumor type.

Germline prevalence of likely pathogenic or pathogenic variants was 21% in the early-onset cancer cohort vs 13% in the young adult cancer cohort (P = .002), with an enrichment of high- and moderate-penetrance pathogenic variants in the early-onset group (15% vs 10%, P = .01). Among patients 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 cancer cohort, TP53 and SDHA mutations were the most common. Among young adult patients with sarcoma, the 18.1% mutation prevalence was similar to the prevalence in the early-onset group.

Conclusion

“Our study demonstrates that the prevalence of inherited cancer susceptibility syndromes in young adults with cancer is not uniform,” said lead study author Dr. Stadler, a medical oncologist at Memorial Sloan Kettering Cancer Center, during a press briefing. “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, the germline mutation prevalence was lower at 13%…. Our results suggest that among patients with early-onset cancers, the increased prevalence of germline mutations support a role for genetic testing irrespective of tumor type.”

Elaine R. Mardis, PhD, FAACR

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 in Columbus, Ohio, said, “Here, the surprising finding is that the germline prevalence of these mutations is significantly higher than we had previously thought. There are 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 adult patients 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 Memorial Sloan Kettering Cancer Center. For full disclosures of the study authors, visit abstractsonline.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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