rs2853676

This case-control study examined TERT gene polymorphisms in a Chinese Li population and found three SNPs significantly associated with COPD risk. The dominant model of rs10069690 showed increased COPD susceptibility (OR=1.56, 95% CI=1.01-2.43, p=0.046), while rs2853677 demonstrated significant associations in both codominant (p=0.033) and dominant models (p=0.009), suggesting TERT polymorphisms contribute to COPD pathogenesis.

This case-control study of 3,754 breast cancer cases and 4,369 controls from admixed US and Mexican women examined telomere length (TL) and nine telomere-related genes. Longer TL was associated with increased breast cancer risk (OR 1.87, 95% CI 1.38-2.55), with strongest association among women with ≥70% Indigenous American ancestry (OR 3.11, 95% CI 1.74-5.67). Multiple SNPs showed associations with breast cancer risk, including TEP1 rs938886 (OR 0.82), TERT rs4246742 (OR 0.85), TERT rs2242652 (OR 1.51), TERF2 rs3785074 (OR 1.13), and TNKS rs6990300 (OR 0.89). Several SNPs showed differential associations by hormone receptor status and genetic ancestry.

Case-control study of 1,555 colon cancer cases and 1,956 controls, plus 754 rectal cancer cases and 959 controls, examining seven TERT SNPs. TERT rs2736118 was associated with increased colon cancer risk (OR=1.31, 95% CI 1.02-1.69), while TERT-CLPTM1L rs2853668 was inversely associated with both colon (OR=0.71, 95% CI 0.55-0.92) and rectal cancer (OR=0.62, 95% CI 0.43-0.90). Three TERT SNPs (rs10069690, rs2242652, rs4246742) showed significant interactions with BMI to influence colon cancer risk, and rs2853668 interacted with aspirin/NSAID use.

Two-stage GWAS of 10,140 lung cancer cases and 11,012 controls in inflammation pathways using hierarchical modeling identified one novel locus at rs2741354 in EPHX2 (p=7.4×10⁻⁶), and confirmed associations with TERT (rs2736100) and HLA region variants. Hierarchical modeling incorporating prior biological knowledge identified 32 replicated variants not captured by conventional maximum likelihood analysis.

Fine-mapping study in Chinese Han population (983 cases, 1,024 controls) identified rs2853677 in TERT significantly associated with glioma risk (adjusted OR 1.96, p=6.8×10⁻⁶). Additionally, a CLPTM1L haplotype G-T-A was associated with increased glioma susceptibility (OR 1.44, p=6.0×10⁻³), suggesting both TERT and CLPTM1L contribute to glioma etiology in this population.

A nested case-control study in the Nurses' Health Study examined associations between 39 SNPs in telomere-maintaining genes (TERT, TRF1, TRF2, TNKS2, POT1) and skin cancer risk in 803 cases (218 melanoma, 285 SCC, 300 BCC) and 870 controls. Two SNPs in TERT (rs2853676 [T] OR=1.43, rs2242652 [A] OR=1.50) and one in TRF1 (rs2981096 [G] OR=1.87) showed significant associations with melanoma risk. The rs401681[C] variant in TERT-CLPTM1L was replicated for melanoma risk (OR=0.73), and was associated with shorter telomere length.

This nested case-control study examined the association between relative telomere length and genetic variants in telomere maintenance genes (TERT, TNKS2, POT1, TERF1, TERF2) with endometrial cancer risk in 674 cases and 1,685 controls. Relative telomere length was not significantly associated with endometrial cancer risk (OR=1.20, 95% CI=0.73-1.96). However, variants rs2736122 in TERT (OR=1.18, 95% CI=1.01-1.38) and rs12412538 in TNKS2 (OR=1.16, 95% CI=1.00-1.34) showed elevated endometrial cancer risk, though these associations did not reach statistical significance after multiple comparisons correction.