rs7726159
mixedMag 5.5This is a intron variant variant in the TERT gene.
Key Literature Trait Associations
Cancer Risk / Telomere Length
In a study of 95,568 Danish individuals (10,895 cancer cases), the telomere-lengthening A allele of rs7726159 was associated with a modest 5% increased overall cancer risk (OR 1.05, 95% CI 1.02–1.09). Risk was strongest for melanoma (OR 1.19) and lung cancer (OR 1.14). The TERT-CLPTM1L region on 5p15.33 is one of the most important genomic regions for cancer susceptibility via telomere length regulation.
Lung cancer
rs7726159-A at the TERT/5p15.33 locus is robustly associated with lung cancer susceptibility, particularly in never-smokers. A large-scale GWAS meta-analysis (PMID 37846649) identified OR=1.42 (95% CI 1.35–1.49, p=1×10⁻⁴⁶) for never-smoking women, making this one of the strongest common lung cancer loci in this subgroup. A broader lung/bronchus cancer GWAS (PMID 40465716) corroborated the association at p=7×10⁻¹⁸. The association is particularly noteworthy in never-smokers where environmental confounding is minimized, underscoring a genuine genetic role for TERT-mediated telomere biology in lung carcinogenesis. A separate analysis also reported genome-wide significant association with respiratory system cancers broadly (p=4×10⁻¹⁹).
Uterine fibroids
rs7726159-A at the TERT locus is associated with increased risk of uterine fibroids (leiomyomata), benign uterine smooth muscle tumours that are the most common gynaecological neoplasm. A 2025 multi-ancestry GWAS meta-analysis (PMID 40050615) reported beta=0.088 (95% CI 0.075–0.101, p=5×10⁻⁴²), placing this among the most statistically significant fibroid loci identified to date. This finding is biologically plausible given that fibroids show somatic TERT promoter mutations and rely on telomerase activation for their prolonged growth. The association was observed across multiple ancestry groups.
Thyroid cancer
rs7726159-A is associated with differentiated thyroid carcinoma (DTC), the most common endocrine malignancy. The EPITHYR consortium multiethnic GWAS (n~3,800; PMID 33527407) replicated the 5p15.33/TERT locus for DTC with OR=1.17 (95% CI 1.09–1.25, p=5×10⁻⁶). A more recent large-scale analysis (PMID 41644669, 2026) reported a beta of 0.1496 at genome-wide significance (p=3×10⁻³¹). The same study also found an association with Graves' disease (an autoimmune thyroid condition) in the opposite direction (beta= −0.0775, p=6×10⁻⁹), suggesting complex pleiotropic effects of TERT variation on thyroid biology. Risk allele frequencies at this locus differ between European and Oceanian populations.
Breast cancer
rs7726159-A at TERT is associated with breast cancer risk, with the clearest evidence in BRCA1 mutation carriers. A 2016 Nature Communications study (PMID 27117709) identified OR=1.07 (95% CI 1.02–1.11, p=3×10⁻⁸) for overall breast cancer in BRCA1 carriers, and a modestly stronger effect for ER-negative breast cancer (OR=1.09, 95% CI 1.05–1.13, p=2×10⁻⁶). This is clinically relevant because BRCA1-associated tumours are predominantly ER-negative and TERT-pathway modifiers may inform personalised surveillance strategies for high-risk women. The effect is modest but genome-wide significant in this high-risk subgroup.
Red blood cell count
rs7726159-A is strongly associated with red blood cell (RBC) count and related haematological indices. Large cross-population GWAS have identified genome-wide significant associations with RBC count (p down to 1×10⁻¹⁰¹), erythrocyte count (p=5×10⁻²⁹ for the C allele), mean corpuscular haemoglobin concentration (beta=0.049, p=4×10⁻¹⁴), and hematocrit (beta=0.013, p=2×10⁻¹⁴). The TERT locus effect on blood cell parameters is mechanistically consistent with telomere length's role in haematopoietic stem cell replication capacity and bone marrow function. These associations have been replicated across European and East Asian populations in studies totalling over 600,000 individuals.
Prostate cancer
In contrast to its risk-increasing effects at lung, thyroid, and uterine sites, rs7726159-A is associated with a modest reduction in prostate cancer risk (OR=0.894, p=4×10⁻⁷; OR=0.899 for late-onset prostate cancer, p=3×10⁻⁶), as identified in a large UK Biobank-based GWAS (n=167,517; PMID 38632662). This inverse relationship between telomere-lengthening alleles and prostate cancer risk has been noted in Mendelian randomisation studies and is consistent with the hypothesis that telomere-driven genomic instability plays a comparatively smaller role in prostate tumour initiation. The A allele may therefore be mildly protective against this specific cancer type.
▶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.
▶ClinVar annotation
Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis
View on ClinVar →▶Research that mentions this SNP (1)
▶Association of human telomerase reverse transcriptase gene polymorphisms, serum levels, and telomere length with renal cell carcinoma risk and pathologyMeta-analysisN=269,720Michela de Martino et al.(2016)· Molecular Carcinogenesis
A meta-analysis of 72 studies comprising 108,248 cases and 161,472 controls found that the TERT rs2736100 T>G polymorphism increases overall cancer risk by 16-39% (OR = 1.17-1.39 across genetic models). Stratified analysis showed strongest associations with lung cancer (OR = 1.24-1.60), and also elevated risk for thyroid cancer, bladder cancer, glioma, myeloproliferative neoplasms, and acute myeloid leukemia, with decreased colorectal cancer risk.
Gene information from NCBI Gene. Variant classifications from ClinVar.
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