Germline Variants in Colorectal Cancer Susceptibility Genes by Race/Ethnicity in Patients With Early-Onset Colorectal Cancer

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In a study reported in the Journal of Clinical Oncology, Seagle et al identified the prevalence of germline colorectal cancer susceptibility gene variants according to race and ethnicity among patients with early-onset colorectal cancer.

Study Details

The study involved patients aged 15 to 49 years at diagnosis of first primary colorectal cancer who underwent germline testing of 14 colorectal cancer susceptibility genes between March 2012 and December 2016 at a clinical testing laboratory (Ambry Genetics). Patients identified as Ashkenazi Jewish, Asian, Black, Hispanic, or White.

Key Findings

Among a total of 3,980 patients with early-onset colorectal cancer, 530 germline pathogenic/likely pathogenic variants were identified in 485 (12.2%).

The prevalence of germline variants was 12.7% in Ashkenazim patients, 9.5% in Asian patients, 10.3% in Black patients, 14.0% in Hispanic patients, and 12.4% in White patients (overall P = .46).

The prevalence of Lynch syndrome varied significantly by race/ethnicity (overall P = .037), ranging from 3.2% in Ashkenazim patients to 9.9% in Hispanic patients.

Significant variation by race/ethnicity was found for prevalence of variants in:

  • APC (overall P < .001), ranging from 0.5% in Asian patients to 7.1% in Ashkenazim patients
  • CHEK2 (overall P = .005), ranging from 0.3% in Black patients to 2.6% in White patients
  • MLH1 (overall P = .008), ranging from 0.8% in Ashkenazim patients to 5.5% in Hispanic patients
  • Monoallelic MUTYH (overall P = .0009), ranging from 0% in Black, Asian, and Ashkenazim patients to 2.4% in White patients
  • PTEN (overall P = .019), ranging from 0% in all groups except Black patients to 0.3% in Black patients.

In adjusted models, Ashkenazim patients were significantly more likely vs White patients to have APC variants (odds ratio [OR] = 8.69, P = .0003) and Hispanic patients were significantly more likely vs White patients to have MLH1 variants (OR = 2.67, P = .007).

The investigators concluded, “Germline genetic features differed by race/ethnicity in young patients with colorectal cancer, suggesting that current multigene panel tests may not be representative of [early-onset] colorectal cancer risk in diverse populations. Further study is needed to optimize genes selected for genetic testing in [early-onset] colorectal cancer via ancestry-specific gene and variant discovery to yield equitable clinical benefits for all patients and to mitigate inequities in disease burden.”

Andreana N. Holowatyj, PhD, MS, of Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the National Institutes of Health, National Human Genome Research Institute, and National Cancer Institute. For full disclosures of the study authors, visit

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®.