rs10069690

A comprehensive gene-environment interaction study in ovarian cancer examining 28 genome-wide significant variants and 7 environmental risk factors (oral contraceptive use, parity, tubal ligation, breastfeeding, menopausal hormone therapy, BMI, endometriosis) in 9,971 cases and 15,566 controls. The strongest multiplicative interaction identified was between rs13255292 and OCP use (P = 3.48 × 10⁻⁴), with differential protective effects by genotype and duration of use, though no interactions remained significant after multiple testing correction.

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.

Age-stratified genome-wide association study of 4,512 glioblastoma cases and 10,582 controls identified age-specific genetic effects on disease susceptibility. SNPs at 7p11.2 (rs723527, rs11979158 near EGFR) showed increased association in older individuals (age 54+, OR=1.28-1.42), while a lower-grade glioma-associated SNP at 8q24.21 (rs55705857) was associated with younger diagnosis (age 18-53, OR=1.76, p=9.30×10−11). IDH1/2 mutations occurred in 15% of younger GBM cases versus 0.8-2.1% in older cases, suggesting many younger cases represent 'secondary GBM' with LGG-like features.

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 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.

A hospital-based case-control study in rural and urban India (1,204 cases; 1,212 controls) examined genetic and lifestyle risk factors for breast cancer. Four SNPs in FGFR2 (rs1219648, rs2420946, rs2981575, rs2981582) showed positive associations with breast cancer (ORs 1.32-1.47). Additional SNPs in obesity and metabolic genes (rs374748 in FBN2, rs2922763 in HNF4G, rs2116830 in KCNMA1, rs11121832 in MTHFR, rs16886165 in MAP3K1, rs11594610 in TCF7L2, rs2274459 in MLN) were associated with increased breast cancer risk. Waist-to-hip ratio ≥0.95 showed strong association (OR 3.78; 95% CI 2.92-4.89), and women living first 20 years in rural areas showed protective effect (OR 0.77).

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.

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 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.