Associations between longer leukocyte telomere length and increased lung cancer risk among never smokers in urban China
Menée à l'aide de données d'études chinoises portant sur 954 témoins et 959 patients atteints d'un cancer du poumon et n'ayant jamais fumé, cette étude analyse l'association entre la longueur des télomères leucocytaires et le risque de développer la maladie
Background: The complex relationship between measured leukocyte telomere length (LTL), genetically-predicted LTL (gTL), and carcinogenesis is exemplified by lung cancer. We previously reported associations between longer pre-diagnostic LTL, gTL, and increased lung cancer risk among European and East Asian populations. However, we had limited statistical power to examine the associations among never smokers by gender and histology. Methods: To investigate further, we conducted nested case-control analyses on an expanded sample of never smokers from the prospective Shanghai Women’s and Men’s Health Studies (SWHS: 798 cases and 792 controls; SMHS: 161 cases and 162 controls). We broke the case-control matching and used multivariable unconditional logistic regression models to estimate the odds ratios (ORs) and 95% confidence intervals (CI) of incident lung cancer and adenocarcinoma (LUAD), in relation to LTL measured using quantitative PCR and gTL determined using a polygenic score. Additionally, we conducted Mendelian Randomization (MR) using MR-PRESSO. Results: We found striking dose-response relationships between longer LTL and gTL, and increased lung cancer risk among never-smoking women (p-trendLTL=4x10-6; p-trendgTL=3x10-4). Similarly among never-smoking men, longer measured LTL was associated with over triple the risk compared to those with the shortest (OR=3.48, 95%CI: 1.85, 6.57). The overall results were similar for LUAD among women and men. MR analyses supported causal associations with LUAD among women (OR1 SD gTL=1.19 (95%CI: 1.03, 1.37; p=0.03). Conclusions: Longer pre-diagnostic leukocyte telomere length is associated with increased lung cancer risk among never smokers. Impact: Our findings firmly support the role of longer telomeres in lung carcinogenesis.