This meta-analysis suggests that the TERT genetic polymorphism rs2853676 is associated with increased risk of glioma, lung adenocarcinoma and ovarian cancer among Caucasians.
In contrast, rs2736100 was associated with other ILD (OR, 1.43; 95% CI, 1.11-1.85; P = 6.2 × 10(-3)) but not with IPF (OR, 1.08; 95% CI, 0.78-1.49; P > 0.05).
The genotype #GA# for rs1695 was recognized to be a protective genotype for glioma (OR, 0.67; 95% CI, 0.47-0.96; P = 0.027), while the genotype #AG# for rs2853676 was shown to be a risk genotype for glioma (OR, 1.50; 95% CI, 1.05-2.15; P = 0.025).
We further evaluated selected SNPs in a replication sample set (83 cases and 535 controls) and found a significant association of an SNP in intron 2 of the TERT gene (rs2736100), which encodes a reverse transcriptase that is a component of a telomerase, with IPF; a combination of two data sets revealed a p value of 2.9 x 10(-8) (GWA, 2.8 x 10(-6); replication, 3.6 x 10(-3)).
As a result, rs2736100 and rs35705950 were associated significantly and independently with ILD as a single phenotype (Odds ratio [OR], 1.29; 95% confidence interval [CI], 1.04-1.60; P = 2 × 10(-2); and OR, 2.22; 95% CI, 1.69-2.92; P = 7 × 10(-9); respectively).
We then found that GRSs used as instrumental variables to predict longer telomere length were associated with increased lung cancer risk (OR = 1.51 (95% CI = 1.34-1.69) for upper vs. lower quartile of the weighted GRS, p value = 4.54 × 10(-14) ) even after removing rs2736100 (p value = 4.81 × 10(-3) ), a SNP in the TERT locus robustly associated with lung cancer risk in prior association studies.
We then found that GRSs used as instrumental variables to predict longer telomere length were associated with increased lung cancer risk (OR = 1.51 (95% CI = 1.34-1.69) for upper vs. lower quartile of the weighted GRS, p value = 4.54 × 10(-14) ) even after removing rs2736100 (p value = 4.81 × 10(-3) ), a SNP in the TERT locus robustly associated with lung cancer risk in prior association studies.
Overall, significantly elevated LC risk was associated with rs2736100, rs401681, rs402710, and rs31489 polymorphisms when all studies were pooled into the meta-analysis.
In conclusion, this meta-analysis demonstrated that TERT rs2736100</span> polymorphism is a risk factor associated with increased lung cancer susceptibility, particularly for lung adenocarcinoma.
In conclusion, this meta-analysis demonstrated that TERT rs2736100</span> polymorphism is a risk factor associated with increased lung cancer susceptibility, particularly for lung adenocarcinoma.
Overall, significantly elevated LC risk was associated with rs2736100, rs401681, rs402710, and rs31489 polymorphisms when all studies were pooled into the meta-analysis.
We identified one novel variant at the level corrected for multiple comparisons (rs2741354 in EPHX2 at 8p21.1 with p value = 7.4 × 10(-6)), and confirmed the associations between TERT (rs2736100) and the HLA region and lung cancer risk.
After the 2nd stage validation (975 cases versus 1022 controls), the study clarified the association that rs2736100 of the TERT gene conferred the highest significant risk of lung cancer (P=4×10(-3) in the 1st stage association, P=4×10(-4) in the 2nd stage validation, and P=1×10(-5), odds ratio=1.24 in the combined population).