rs17879961
mixedMag 5.5This is a variant in the CHEK2 gene that changes a isoleucine to an threonine.
Key Literature Trait Associations
Lung cancer
The rare A allele at rs17879961 (CHEK2 I157T) is associated with increased lung cancer risk, with the effect most pronounced for squamous cell lung carcinoma. A 2014 Nature Genetics study (11,348 cases, 15,861 controls discovery; 10,246 cases, 38,295 controls replication) reported OR=1.67 (p=3×10⁻¹¹) for overall lung cancer and OR=2.63 (p=1×10⁻¹³) for squamous cell carcinoma. A 2024 multi-ancestry GWAS meta-analysis (42,102 cases, 181,270 controls) independently confirmed the signal at OR=1.55 (p=6×10⁻¹³) for overall lung cancer and OR=2.59 (p=3×10⁻¹⁸) for squamous cell subtype. This is notably a loss-of-function variant increasing cancer susceptibility via reduced CHEK2-mediated DNA damage control.
Breast Cancer Risk
The CHEK2 I157T variant (rs17879961-G) is consistently associated with elevated breast cancer risk across multiple large studies. A 2012 meta-analysis of 19,621 cases and 27,001 controls reported an overall OR of 1.48 (95% CI 1.31–1.66), with substantially higher risk for lobular breast cancer (OR 4.17, 95% CI 2.89–6.03). A broader 2013 multi-cancer meta-analysis confirmed an OR of 1.58 (95% CI 1.42–1.75) for breast cancer specifically. A large 2017 GWAS (>122,000 cases) and a 2019 reanalysis of ~279,000 women of Asian and European ancestry both validated the signal at genome-wide significance. The association is most prominent in European-ancestry populations.
Thyroid cancer
rs17879961-G in CHEK2 is associated with increased thyroid cancer risk, identified in a very large 2026 multi-ancestry GWAS encompassing ~2.9 million genomes across 19 biobanks. The GWAS Catalog reports a beta of 0.7511 (p=7×10⁻¹³) in the multi-ancestry analysis (21,816 cases, 2,895,812 controls) and beta=0.7841 (p=1×10⁻¹³) in the European-only subset (14,764 cases, 2,091,602 controls). These correspond to an OR of approximately 2.1 on the log-odds scale, making this one of the stronger common-variant associations for thyroid cancer. The signal was identified in a study cataloging 883 total loci for thyroid diseases.
Colorectal Cancer Risk
CHEK2 I157T (rs17879961-G) is associated with increased colorectal cancer (CRC) risk, particularly in European populations. A 2012 systematic review and meta-analysis of 7 studies (4,029 cases, 13,844 controls) estimated an overall OR of 1.61 (95% CI 1.40–1.87), with familial CRC showing a stronger effect (OR 1.97, 95% CI 1.41–2.74) compared to sporadic CRC (OR 1.48, 95% CI 1.23–1.77). The broader 2013 I157T meta-analysis likewise found OR 1.67 (95% CI 1.24–2.26) for colorectal cancer. A 2022 clinical genetics framework review supports offering colonoscopy surveillance to I157T carriers with a family history of CRC, reflecting the moderate but clinically relevant penetrance of this allele.
Aerodigestive squamous cell carcinoma
Paradoxically, rs17879961-G (CHEK2 I157T) is associated with reduced risk of aerodigestive squamous cell cancers (head, neck, esophagus) in a large European GWAS meta-analysis. Lesseur et al. (2021) reported OR=0.43 (p=1×10⁻¹⁵) among 13,887 cases and 61,961 controls, with the protective effect attributed to the CHEK2 locus. This inverse relationship—risk-increasing for lung squamous cell carcinoma via the A allele, but risk-decreasing for upper aerodigestive squamous cancers via the G allele—likely reflects tissue-specific differences in how CHEK2 dysfunction interacts with tobacco-related carcinogenesis.
Prostate cancer
CHEK2 I157T (rs17879961-G) is associated with moderately elevated prostate cancer risk in European men. A 2015 systematic review and meta-analysis of 8 studies found OR=1.80 (95% CI 1.51–2.14) for I157T carriers, indicating a roughly 80% increase in relative risk. The broader multi-cancer meta-analysis by Han et al. (2013) also identified prostate cancer as one of the elevated-risk phenotypes for I157T. The variant's effect appears strongest in familial prostate cancer cohorts, consistent with CHEK2's role as a moderate-penetrance cancer predisposition gene.
Myeloproliferative neoplasms
rs17879961-G in CHEK2 is associated with elevated risk of myeloproliferative neoplasms (MPNs), a group of clonal hematopoietic stem cell disorders including polycythemia vera, essential thrombocythemia, and myelofibrosis. A 2020 Nature GWAS (3,797 MPN cases, 1,152,977 controls) identified CHEK2 as one of 17 MPN risk loci (OR=2.23, p=1×10⁻⁷) and demonstrated through functional assays that CHEK2 variants alter hematopoietic stem cell biology. This finding links the DNA damage checkpoint role of CHEK2 to clonal hematopoiesis and MPN pathogenesis.
▶GWAS Catalog Trait Associations (10)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
GWAS Catalog Trait Associations (10)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
polycystic ovary syndrome
squamous cell lung carcinoma
upper aerodigestive tract neoplasm
squamous cell carcinoma
thyroid carcinoma
lung cancer
lung carcinoma
uterine fibroid
female infertility
breast carcinoma
▶ClinVar annotation
Adrenal cortex carcinoma; Bone osteosarcoma; Breast and colorectal cancer, susceptibility to; Breast and/or ovarian cancer; CHEK2-related cancer predisposition; CHEK2-related disorder; Colorectal cancer; Familial cancer of breast; Familial prostate cancer; Gastrointestinal carcinoma; Hereditary cancer-predisposing syndrome; Li-Fraumeni syndrome 2 (TPDS4); Malignant tumor of breast; Malignant tumor of prostate; Predisposition to cancer; TUMOR PREDISPOSITION SYNDROME 4, BREAST/PROSTATE/COLORECTAL; not specified
View on ClinVar →▶Research that mentions this SNP (1)
▶Prevalence and Spectrum of Germline Cancer Susceptibility Gene Mutations Among Patients With Early-Onset Colorectal CancerAssociationN=450Pearlman R. et al.(2017)· JAMA Oncology
A prospective cohort study of 450 patients with early-onset colorectal cancer (diagnosed before age 50) identified 72 patients (16%) with pathogenic mutations in cancer susceptibility genes, including 37 with Lynch syndrome (MLH1, MSH2, MSH6, PMS2). The study found that multigene panel testing identified mutations in 33.3% of patients who did not meet conventional genetic testing criteria, suggesting that broad multigene panel testing should be considered for all early-onset CRC patients.
Gene information from NCBI Gene. Variant classifications from ClinVar.
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