Adult solid tumours cancer susceptibility

Gene: CHEK2

Green List (high evidence)

Comment on list classification: There are numerous individuals reported with CHEK2 variants and solid tumors e.g., in breast, thyroid, and prostate cancer. Hence, this gene will be suggested for promotion to Green on Adult solid tumours cancer susceptibility, with a request of expert review to determine if the gene fits into panel scope.

Created: 17 Jun 2026, 2:20 p.m. | Last Modified: 17 Jun 2026, 2:41 p.m.

Panel Version: 2.39

PMID: 40335619 Stubbins et al., 2025
Cohort of patients with hereditary hematopoietic malignancies. 57 probands had germline P/LP CHEK2 variants, mostly p.I157T (53%, 30/57). Among CHEK2 p.I157T carriers, 43% (19/44) had myeloid malignancies, 32% (14/44) had lymphoid malignancies, and 2% (1/44) had both. Among those with other germline P/LP CHEK2 alleles, 36% (13/36) had myeloid malignancies, 28% (10/36) had lymphoid malignancies, and 6% (2/36) had both. CHEK2 p.I157T was enriched in HM patients (OR 6.44, 95%CI 3.68–10.73, P < 0.001).
In a solid tumor risk cohort, 36% (15/42) of CHEK2 p.I157T patients had a HM family history.

PMID: 39966186 Weis et al., 2025
Description of 12 patients - Brazilian women with early-stage breast cancer and CHEK2 variants (9/12 with onset before age 50yrs, and 9/12 had family history of breast cancer). 7 patients had intronic CHEK2 variants; the most common variant in this group was CHEK2: c.349A>G, p.Arg117Gly (4 patients).

PMID: 36360192 Kirchner et al., 2022
Study of a cohort of 150 Croatian men with prostate cancer, plus 442 cancer-free controls. 4/150 individuals harboured a P/LP variant in CHEK2, and developed prostate cancer on average almost 9 years earlier than individuals without CHEK2 variants.

PMID: 25798211 Kaczmarek-Rys et al., 2015
Polish cohort of 602 thyroid carcinoma patients and 829 controls. CHEK2 c.470 T > C (p.I157T, rs17879961) variant increases risk of thyroid carcinoma in Greater Poland population: increases the risk of developing differentiated thyroid cancer almost twice (OR = 1.81, p = 0.004), and the risk of papillary thyroid carcinoma in female patients homozygous for the c.470C allele was shown to increase almost 13-fold (OR = 12.81, p = 0.019).

CHEK2 is associated with Tumor predisposition syndrome 4, breast/prostate/colorectal, OMIM:609265 (OMIM accessed 17th Jun 2026. The association between CHEK2 and AD CHEK2-related cancer predisposition was classified as Definitive in ClinGen (Hereditary Cancer GCEP, Nov 2024).

Created: 17 Jun 2026, 2:17 p.m. | Last Modified: 17 Jun 2026, 2:57 p.m.

Panel Version: 2.39

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Tumor predisposition syndrome 4, breast/prostate/colorectal, OMIM:609265

Publications

• 25798211
• 39966186
• 40335619

Comment on list classification: Demoted this gene from Green to Amber due to feedback from Lara Hawkes and Clare Turnbull (Cancer Clinical Team, Genomics England), that this gene confers a moderate risk.

Created: 20 Aug 2018, 11:54 a.m.

Green List (high evidence)

Tumor Suppressor. Biallelic phenotype.

Created: 5 Jul 2017, 12:19 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Breast cancer