RT Journal Article SR Electronic T1 Variation in oral microbiome is associated with future risk of lung cancer among never-smokers JF Thorax JO Thorax FD BMJ Publishing Group Ltd and British Thoracic Society SP 256 OP 263 DO 10.1136/thoraxjnl-2020-215542 VO 76 IS 3 A1 H Dean Hosgood A1 Qiuyin Cai A1 Xing Hua A1 Jirong Long A1 Jianxin Shi A1 Yunhu Wan A1 Yaohua Yang A1 Christian Abnet A1 Bryan A Bassig A1 Wei Hu A1 Bu-Tian Ji A1 Madelyn Klugman A1 Yongbing Xiang A1 Yu-Tang Gao A1 Jason YY Wong A1 Wei Zheng A1 Nathaniel Rothman A1 Xiao-Ou Shu A1 Qing Lan YR 2021 UL http://thorax.bmj.com/content/76/3/256.abstract AB Objective To prospectively investigate whether diversity in oral microbiota is associated with risk of lung cancer among never-smokers.Design and setting A nested case–control study within two prospective cohort studies, the Shanghai Women’s Health Study (n=74 941) and the Shanghai Men’s Health Study (n=61 480).Participants Lifetime never-smokers who had no cancer at baseline. Cases were subjects who were diagnosed with incident lung cancer (n=114) and were matched 1:1 with controls on sex, age (≤2 years), date (≤30 days) and time (morning/afternoon) of sample collection, antibiotic use during the week before sample collection (yes/no) and menopausal status (for women).Main outcomes and measures Metagenomic shotgun sequencing was used to measure the community structure and abundance of the oral microbiome in pre-diagnostic oral rinse samples of each case and control. Multivariable logistic regression models were used to estimate the association of lung cancer risk with alpha diversity metrics and relative abundance of taxa. The Microbiome Regression-Based Kernel Association Test (MiRKAT) evaluated the association between risk and the microbiome beta diversity.Results Subjects with lower microbiota alpha diversity had an increased risk of lung cancer compared with those with higher microbial alpha diversity (Shannon: ptrend=0.05; Simpson: ptrend=0.04; Observed Species: ptrend=0.64). No case–control differences were apparent for beta diversity (pMiRKAT=0.30). After accounting for multiple comparisons, a greater abundance of Spirochaetia (ORlow 1.00 (reference), ORmedium 0.61 (95% CI 0.32 to 1.18), ORhigh 0.42 (95% CI 0.21 to 0.85)) and Bacteroidetes (ORlow 1.00 (reference), ORmedium 0.66 (95% CI 0.35 to 1.25), ORhigh 0.31 (95% CI 0.15 to 0.64)) was associated with a decreased risk of lung cancer, while a greater abundance of the Bacilli class (ORlow 1.00 (reference), ORmedium 1.49 (95% CI 0.73 to 3.08), ORhigh 2.40 (95% CI 1.18 to 4.87)) and Lactobacillales order (ORlow 1.00 (reference), ORmedium 2.15 (95% CI 1.03 to 4.47), ORhigh 3.26 (95% CI 1.58 to 6.70)) was associated with an increased risk of lung cancer.Conclusions Our prospective study of never-smokers suggests that lower alpha diversity was associated with a greater risk of lung cancer and the abundance of certain specific taxa was associated with altered risk, providing further insight into the aetiology of lung cancer in the absence of active tobacco smoking.