What you carry at this position in your DNA and what research says about it.
Cancer Risk Trade-Off: 9/10 evidence, 21 publications.
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Sample genotype (not yours): A/A
Typical Cancer Risk Profile
This genotype represents the standard genetic baseline for the majority of the population. It carries typical risks for breast and reproductive conditions but lacks the protective effect against lung and kidney cancers.
What this genotype means: Typical baseline risk for breast cancer; Typical baseline risk for lung and kidney cancers; Standard risk for female reproductive conditions.
Sample genotype (not yours): A/G
Mixed Cancer Risk Profile
Carrying one copy of the variant presents a complex trade-off in cancer susceptibility. It moderately increases the risk of breast and reproductive conditions while significantly lowering the risk of lung and kidney cancers.
What this genotype means: Moderately increased risk of breast cancer; Significantly lower risk of lung and kidney cancers; Slightly higher risk of female reproductive conditions.
Sample genotype (not yours): G/G
Pronounced Mixed Cancer Risk Profile
Carrying two copies of the variant amplifies both the risks and the protective effects. It further elevates breast and reproductive risks while offering strong protection against lung and kidney cancers.
What this genotype means: Elevated risk of breast cancer; Strongly reduced risk of lung and kidney cancers; Increased risk of female reproductive conditions.
Gene function and biological role
Gene Function: The CHEK2 gene encodes checkpoint kinase 2, a vital tumor suppressor protein that regulates cell division and monitors DNA integrity. When DNA damage occurs, this kinase is activated to halt the cell cycle, allowing time for repairs, or to trigger programmed cell death if the damage is too severe. Impaired function of this protein can allow cells with damaged DNA to divide uncontrollably, potentially leading to tumor development. Consequently, inherited alterations in this gene are widely recognized as risk factors for several types of cancer.
Variant Impact: The rs17879961 variant, commonly known as p.Ile157Thr, results in an amino acid substitution in the forkhead-associated domain of the CHEK2 protein. This specific structural change alters the protein's ability to bind to its target substrates, reducing its overall activity in DNA repair pathways. Interestingly, this reduction in activity has contrasting effects depending on the tissue type. While it increases susceptibility to hormone-related cancers like breast cancer, it simultaneously decreases the risk of tobacco-related squamous cell cancers.
Key Insight: This variant presents a rare genetic trade-off, increasing the risk of breast cancer while significantly reducing the risk of lung and kidney cancers.
Location: CHEK2. Chromosome 22 · 22q12.1 · 28.7 Mb
Estimated prevalence by population
Global 99.2%; European 98.9%; African 100.0%; East Asian 100.0%; South Asian 100.0%; Americas > 99.9%; Ashkenazi 99.9%; Finnish 95.5%; Middle Eastern 100.0%; Amish 100.0%.
Estimated AA genotype frequency.
Global 0.8%; European 1.1%; African 0.0%; East Asian 0.0%; South Asian 0.0%; Americas < 0.1%; Ashkenazi 0.1%; Finnish 4.5%; Middle Eastern 0.0%; Amish 0.0%.
Estimated AG genotype frequency.
Global < 0.1%; European < 0.1%; African 0.0%; East Asian 0.0%; South Asian 0.0%; Americas < 0.1%; Ashkenazi < 0.1%; Finnish 0.1%; Middle Eastern 0.0%; Amish 0.0%.
Estimated GG genotype frequency.
Showing effects for A/A genotype
Cancer & Oncology
Breast Cancer
Breast Cancer. Evidence: 9/10. Source: PMID 29059683. Typical Risk.
Lung Cancer
Lung Cancer. Evidence: 9/10. Source: PMID 24880342. Typical Risk.
Blood Cancers
Myeloproliferative Disorders. Evidence: 4/10. Source: PMID 33057200. Typical Risk.
Endocrine & Reproductive
Female Reproductive Health & Fertility
Female Infertility. Evidence: 7/10. Source: PMID 40229599. Typical Risk.
Polycystic Ovary Syndrome. Evidence: 8/10. Source: PMID 40069456. Typical Risk.
Showing effects for A/G genotype
Breast Cancer. Evidence: 9/10. Source: PMID 29059683. ~1.3x Increased Risk.
Lung Cancer. Evidence: 9/10. Source: PMID 24880342. ~60% Lower Risk.
Myeloproliferative Disorders. Evidence: 4/10. Source: PMID 33057200. ~2.2x Increased Risk.
Female Infertility. Evidence: 7/10. Source: PMID 40229599. ~1.35x Increased Risk.
Polycystic Ovary Syndrome. Evidence: 8/10. Source: PMID 40069456. ~1.6x Increased Risk.
Showing effects for G/G genotype
Breast Cancer. Evidence: 9/10. Source: PMID 29059683. Increased Risk.
Lung Cancer. Evidence: 9/10. Source: PMID 24880342. Lower Risk.
Myeloproliferative Disorders. Evidence: 4/10. Source: PMID 33057200. Increased Risk.
Female Infertility. Evidence: 7/10. Source: PMID 40229599. Increased Risk.
Polycystic Ovary Syndrome. Evidence: 8/10. Source: PMID 40069456. Increased Risk.
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
Most people carry this standard genotype, which represents the baseline risk for various health conditions. Without the altered variant, there is no elevated genetic risk for breast cancer, female infertility, or polycystic ovary syndrome from this specific marker. However, this baseline status also means lacking the unique protective effect against tobacco-related cancers that the variant allele provides. Research indicates that individuals with this genotype have typical, unreduced risks for lung cancer and upper aerodigestive tract cancers. Maintaining standard cancer screenings and avoiding tobacco smoke remain the most effective ways to manage health risks. Routine clinical guidelines for breast health and standard checkups are appropriate for this profile. There are no special genetic precautions required beyond standard lifestyle recommendations. Overall, this represents the most common and well-understood genetic baseline.
Typical baseline risk for breast cancer; Typical baseline risk for lung and kidney cancers; Standard risk for female reproductive conditions.
Sample genotype: AG (Heterozygous)
Inheriting one copy of the variant allele introduces a fascinating biological trade-off. Clinical studies show a moderate increase in susceptibility to breast cancer, with an odds ratio of approximately 1.3. It is also associated with higher risks for female reproductive conditions like infertility and polycystic ovary syndrome. Conversely, this altered protein function appears to protect against tobacco-related malignancies. The risk of developing lung cancer and upper aerodigestive tract cancers is reduced by more than half compared to the general population. This protective effect may stem from damaged lung cells undergoing alternative cell death pathways rather than replicating. Despite the lower lung cancer risk, avoiding smoking remains crucial for overall cardiovascular and respiratory health. Discussing these mixed risks with a healthcare provider can help tailor a personalized screening plan.
Moderately increased risk of breast cancer; Significantly lower risk of lung and kidney cancers; Slightly higher risk of female reproductive conditions.
Sample genotype: GG (Homozygous)
Having two copies of this variant is extremely rare in almost all populations. This double-variant status is expected to further compromise the standard DNA repair pathway, leading to a more pronounced risk profile. Susceptibility to breast cancer and other hormone-sensitive conditions is elevated compared to carrying just one copy. At the same time, the protective effect against squamous cell lung cancer and kidney cancer is highly pronounced. Because the CHEK2 protein's binding ability is severely reduced, cells damaged by environmental toxins like tobacco smoke are highly unlikely to survive and form tumors. This unique cellular vulnerability prevents the initiation of specific tobacco-related cancers. However, the elevated risk for other cancers makes proactive screening and regular clinical consultations highly advisable. Tailoring a health strategy with a genetic counselor can help manage these contrasting risks effectively.
Elevated risk of breast cancer; Strongly reduced risk of lung and kidney cancers; Increased risk of female reproductive conditions.
Variants with shared genetic architecture
rs738722 · CHEK2 Gene · Chr 22 · Esophageal Cancer Risk
rs11571833 · BRCA2 Gene · Chr 13 · Cancer Risk
rs180177132 · PALB2 Gene · Chr 16 · Hereditary Cancer Risk
Content updated August 2026.
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