rs2736098

This case-control association study analyzed 10 telomere-length-associated SNPs in relation to pancreatic cancer risk in 2,374 cases and 4,326 controls from the PANDoRA consortium. The strongest association was with TERT-rs2736100 (OR=1.54, p=1.54×10⁻¹⁰), and a novel protective association was found with NAF1-rs7675998 (OR=0.80, p=1.87×10⁻⁶). A genetic telomere length score (teloscore) combining these variants reached genome-wide significance for PDAC risk (p=2.98×10⁻⁹ for highest vs. lowest quintile).

Meta-analysis of 204,993 SNPs in 22 telomere structure and maintenance genes identified 13 independent SNPs associated with colorectal, breast, prostate, ovarian, and lung cancer risk in 61,851 cases and 74,457 controls of European descent. Seven of these associations were novel findings. Notable findings include rs12655062 (positively associated with prostate cancer, inversely with colorectal/ovarian cancers), rs75316749 (positively associated with colorectal, breast, ovarian, and lung cancers), rs974404 and rs12144215 in DCLRE1B (inversely associated with prostate/lung and colorectal/breast/ovarian cancers respectively), rs34978822 in RTEL1 (inversely associated with prostate/lung cancers), and rs116895242 near POT1 (inversely associated with colorectal, ovarian, and lung cancers).

Case-control study of 828 Chinese Han participants (410 NSCLC cases, 418 controls) examining TERT gene polymorphisms and their SNP-SNP interactions on non-small cell lung cancer risk. Carriers of the G allele at rs2736100 showed increased NSCLC risk (OR=1.68, 95% CI: 1.28-2.07), as did carriers of the A allele at rs2736098 (OR=1.52, 95% CI: 1.19-1.93). A significant gene-gene interaction was found between rs2736098 and rs2736100 (OR=2.52, 95% CI: 1.68-3.68 for GA/AA and TG/GG combined genotypes versus reference).

A case-case association study of 18,343 prostate cancer patients (16,515 European, 1,828 African-American) evaluating 36 validated PC-risk SNPs found that rs2735839 (G allele) on chromosome 19q13 in the KLK3 gene was significantly and inversely associated with aggressive disease and high Gleason scores in both populations (p = 9.343 × 10⁻⁸ overall, p = 1.042 × 10⁻⁵ European, p = 2.0 × 10⁻⁴ African-American).

This case-control study of 231 bladder urothelial carcinoma (UC) patients and 261 benign controls found that rs9642880[T] and rs798766[T] variants increase bladder-UC risk (OR=1.72, p=0.028 and OR=1.84, p=0.01 respectively), but unlike upper tract UC, these variants are not associated with disease aggressiveness (grade or stage). The findings highlight distinct genetic differences between bladder-UC and upper urinary tract urothelial carcinoma.

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.

This case-control study of 218 Egyptian breast cancer patients and 178 healthy controls examined associations between hTERT polymorphisms and breast cancer risk. The GG genotype and G allele of hTERT rs2736098G>A were significantly associated with increased breast cancer risk (OR=7.484, p≤0.001; OR=1.743, p=0.006), as was the rs2735940 TT genotype (OR=1.519, p=0.045). The MNS16A tandem repeat showed no significant association. Telomere length was significantly reduced in breast cancer patients younger than 40 years compared to age-matched controls.

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.

This review discusses recent genome-wide association studies (GWAS) that identified five susceptibility loci for glioma: TERT rs2736100 (OR=1.27), CCDC26 rs4295627 (OR=1.36), CDKN2A/CDKN2B rs4977756 (OR=1.24), RTEL1 rs6010620 (OR=1.18), and PHLDB1 rs498872 (OR=1.28). The combined effect shows that individuals with 8 or more risk alleles have over 3-fold increased glioma risk compared to those with median alleles (OR=1.31 per allele, p=1.39×10^-74). These common low-risk variants represent the strongest evidence to date for inherited susceptibility to glioma, with shared associations across multiple cancer types.

Case-control study examining associations between cell cycle gene polymorphisms and non-Hodgkin lymphoma (NHL) overall and subtypes. Studied 10 SNPs in genes including BCL6 (rs1056932), CCND1 (rs603965, rs678653), CCNH (rs2266690), CDKN2A (rs3731249, rs11515, rs3088440), CHEK1 (rs506504), LMO2 (rs2038602, rs3740617), and TERT (rs2736098, rs2853690). Notable associations included CCND1 rs603965 with increased NHL risk (p trend=0.021) and CCND1 rs603965 AA genotype with DLBCL (OR=1.4, 95% CI 1.0-2.0).