PT  - JOURNAL ARTICLE
AU  - H Dean Hosgood
AU  - Qiuyin Cai
AU  - Xing Hua
AU  - Jirong Long
AU  - Jianxin Shi
AU  - Yunhu Wan
AU  - Yaohua Yang
AU  - Christian Abnet
AU  - Bryan A Bassig
AU  - Wei Hu
AU  - Bu-Tian Ji
AU  - Madelyn Klugman
AU  - Yongbing Xiang
AU  - Yu-Tang Gao
AU  - Jason YY Wong
AU  - Wei Zheng
AU  - Nathaniel Rothman
AU  - Xiao-Ou Shu
AU  - Qing Lan
TI  - Variation in oral microbiome is associated with future risk of lung cancer among never-smokers
AID  - 10.1136/thoraxjnl-2020-215542
DP  - 2021 Mar 01
TA  - Thorax
PG  - 256--263
VI  - 76
IP  - 3
4099  - http://thorax.bmj.com/content/76/3/256.short
4100  - http://thorax.bmj.com/content/76/3/256.full
SO  - Thorax2021 Mar 01; 76
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.