Patients with Early-Onset Cancer at Higher Risk for Harboring Germline Mutations

Study presented at the AACR Virtual Annual Meeting II supports an increased role for genetic testing in these patients.

Patients aged 18-39 with early-onset cancer were found to be at a higher risk of harboring germline mutations when compared with patients with young-adult cancers, according to a study presented at the American Association for Cancer Research (AACR) Virtual Annual Meeting II, held online June 22-24.1-2

The investigators found that 21% of patients with early-onset cancer, most typically breast or colorectal cancers, had an inherited genetic mutation, vs 13% of patients with young-adult cancer (P = 0.002).1

“From the genetic perspective, it would appear that young-adult patients with early-inset cancer… have a much higher prevalence of germline mutations than other types of young-adult cancer patients,” said lead investigator Zsofia K. Stadler, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center during a presentation. “Suggesting that young-adults with early-onset cancer should be genetically tested.”

The study looked at germline mutations in 1201 young adult patients who received a cancer diagnosis. Of those, 877 were patients with early-onset cancer, and 324 were patients with young-adult cancer types.

For the purposes of the study, early-onset cancers were classified 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.

The most common early-onset cancer type was breast cancer (39%, n=342) and colorectal cancer (20%, n=179). Additional common cancer types were kidney cancer (6%, n=53), ovarian cancer (6%, n=50) and pancreatic cancer (6%, n=50).

The most frequent mutations occurred in the genes BRCA1, BRCA2, ATM, CHEK2, and the Lynch syndrome-associated genes. The highest rates of genetic mutations were found patients with cancer in the pancreas, breast, or kidney, and patients with early-onset cancer demonstrated a higher prevalence of high- and moderate-penetrance gene mutations when compared with young-adults with cancer (15% vs 10%, respectively; p=0.01).

“This study highlights that genetic susceptibility among young cancer patients is heterogeneous,” said Stadler in a press release.2 “The distinct set of germline variants appear to suggest that patients with early-onset cancers harbor mutations similar to those also found in older individuals with cancer, but at a higher prevalence.”

“In the context of this germline setting, there are now treatment implications for these individuals… if the mutations are such that they preclude or portend a high mutation rate in the incident tumors,” added Elaine Mardis, PhD, past president of the AACR during a press conference after the presentation. “From the standpoint of primary into recurrent disease we would want to do accelerated imaging, and in some cases even liquid biopsy-based assays at specific intervals to understand whether there’s recurrent cancer in play.”

The investigators noted that being a single-institution study was a limitation, leading to the possibility of some cancer types being under- or over-represented. The analysis was also limited to solid tumors only and did not assess the risk in young patients with hematological malignancies.


1. Stadler ZK, Maio A, Padunan A, et al. Germline mutation prevalence in young adults with cancer. Presented at: American Association for Cancer Research Virtual Annual Meeting II; June 22, 2020.

2. Young Adults With Cancer May Harbor Germline Mutations [news release]. Published June 22, 2020.