Phenotypic and genetically predicted leucocyte telomere length and lung cancer risk in the prospective UK Biobank

Abstract

We investigated phenotypic leucocyte telomere length (LTL), genetically predicted LTL (gTL), and lung cancer risk among 371 890 participants, including 2829 incident cases, from the UK Biobank. Using multivariable Cox regression, we found dose-response relationships between longer phenotypic LTL (p-trend continuous =2.6×10 -5), longer gTL predicted using a polygenic score with 130 genetic instruments (p-trend continuous =4.2×10 -10), and overall lung cancer risk, particularly for adenocarcinoma. The associations were prominent among never smokers. Mendelian Randomization analyses supported causal associations between longer telomere length and lung cancer (HR per 1 SD gTL =1.87, 95% CI: 1.49 to 2.36, p=4.0×10 -7), particularly adenocarcinoma (HR per 1 SD gTL =2.45, 95%CI: 1.69 to 3.57, p=6.5×10 -6).