rs401681

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).

Genome-wide association meta-analysis of cutaneous melanoma combining pathologically confirmed cases with 23andMe self-reported cases identified 54 genome-wide significant loci. The study confirmed 19 of 21 previously reported loci, revealed complex LD structure at the AHR/AGR3 region (rs117132860, p=3.8×10−21), and identified novel associations including those near MFSD12/FZR1. Key variants included rs12215602 (IRF4), rs16953002 and rs62034121 (FTO), and variants associated with pigmentation phenotypes (hair color, nevus count, sunburn susceptibility).

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).

Meta-analysis of 27 case-control studies (60,828 cases, 109,135 controls) examining CLPTM1L variants rs402710 and rs401681 at chromosome 5p15.33 and lung cancer susceptibility. Both SNPs showed significant increased lung cancer risk with per-allele ORs of 1.14 (95% CI 1.11-1.16, P<10^-5) for rs401681 and 1.15 (95% CI 1.12-1.19, P<10^-5) for rs402710. Associations were consistent across Caucasian and East Asian populations, histological types, and smoking status.

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.

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.

Meta-analysis of 45,184 subjects (5,469 cases, 39,715 controls) showing that the TERT-CLPTM1L rs401681[C] allele is associated with increased non-melanoma skin cancer risk overall (OR 1.13, 95% CI 1.07-1.20), with strongest association for basal cell carcinoma (OR 1.19, 95% CI 1.11-1.27) but not squamous cell carcinoma (OR 1.01, 95% CI 0.91-1.21) in white populations.

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 meta-analysis of 26 articles with 30,770 cases and 34,089 controls for rs402710 and 38 articles with 67,849 cases and 328,226 controls for rs401681 found that both CLPTM1L gene polymorphisms are significantly associated with decreased overall cancer risk (rs402710 allele contrast: OR = 0.88, 95% CI = 0.84-0.92; rs401681 allele contrast: OR = 0.93, 95% CI = 0.89-0.97). The association was particularly strong for lung cancer among Asians, with rs402710 showing OR = 0.85 (95% CI = 0.81-0.89) and rs401681 showing OR = 0.86 (95% CI = 0.84-0.89).

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 Iranian case-control study examined the association between the IGFBP-3 A-202C polymorphism (rs2854744) and bladder cancer risk in 162 cancer patients and 324 controls. The study found that the AA genotype was protective against bladder cancer (OR=0.48, 95% CI 0.24-0.64, P=0.001) while the AC genotype increased risk (OR=1.76, 95% CI 1.27-2.84, P=0.038). The protective effect of the AA genotype was more pronounced in advanced bladder cancers, with no AA genotype carriers having high-grade tumors.

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.