Germline pathogenic variants (PVs) in CHEK2 are associated with similar cancer phenotypes, regardless of the variant type, according to a study published in JAMA Oncology.

With few exceptions, CHEK2 PVs were associated with breast, kidney, and thyroid cancers, but not colorectal cancer, researchers found. 

For this study, the researchers retrospectively examined lab results from 3783 patients with CHEK2 PVs identified using multigene cancer panel testing (MGPT). Of these patients, 92% were women, and most self-reported White race.

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Looking at specific variants, breast cancer was less frequent in patients with p.I157T (odds ratio [OR], 0.66; 95% CI, 0.56-0.78; P <.001), p.S428F (OR, 0.59; 95% CI, 0.46-0.76; P <.001), and p.T476M (OR, 0.74; 95% CI, 0.56-0.98; P =.04) PVs compared with other identified PVs. 

Among patients with breast cancer, those with PVs were more likely to have bilateral breast cancers, more estrogen- and/or progesterone receptor-positive disease, and more ERBB2-positive disease.

After excluding p.I157T, p.S428F, and p.T476M, patients with monoallelic CHEK2 PVs were younger at first cancer diagnosis (P <.001) and were more likely to have breast (OR, 1.83), thyroid (OR, 1.63), or kidney cancer (OR, 2.57), compared with patients who had negative MGPT. 

Patients with CHEK2 PVs were less likely to develop colorectal cancer (OR, 0.62), compared with those who had negative MGPT. Endometrial cancer and pancreatic cancer were also less frequent in the PV cohort than in patients with negative MGPT.

The researchers concluded that these results should “inform genetic counseling and risk assessment of patients with CHEK2 PVs.”

Disclosures: The study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Bychkovsky BL, Agaoglu NB, Horton C, et al. Differences in cancer phenotypes among frequent chek2 variants and implications for clinical care — checking CHEK2. JAMA Oncol. Published online September 22, 2022. doi:10.1001/jamaoncol.2022.4071