Abstract
The association between adult height and risk of lung cancer has been investigated by epidemiology studies, but the results are inconsistent. Mendelian randomization (MR) analyses with individual-level data from two genome-wide association studies, including a total of 7127 lung cancer cases and 6818 controls, were carried out to explore whether adult height is causally associated with risk of lung cancer. A weighted genetic risk score (wGRS) was created based on genotypes of 101 known height-associated genetic variants. Association between the wGRS and risk of lung cancer was analyzed by logistic regression for each study separately. The combined effect was calculated using fixed effect meta-analysis. MR analyses showed that increased risk of lung cancer (OR = 1.19, 95%CI: 1.05-1.35, P = 0.006) associated with taller genetically determined height. Compared with individuals in the lowest tertile of the height-associated wGRS, those in the highest tertile had 1.10-fold (95% CI: 1.01-1.20) increased risk of developing lung cancer. Sensitivity analyses excluding BMI-associated genetic variants demonstrated consistent association. Our study suggested that genetically taller height was associated with increased risk of lung cancer in East Asian population, indicating that increasing height may have a causal role in lung cancer carcinogenesis.