Variation in oral microbiome is associated with future risk of lung cancer among never-smokers

H. Dean Hosgood, Qiuyin Cai, Xing Hua, Jirong Long, Jianxin Shi, Yunhu Wan, Yaohua Yang, Christian Abnet, Bryan A. Bassig, Wei Hu, Bu Tian Ji, Madelyn Klugman, Yongbing Xiang, Yu Tang Gao, Jason Y.Y. Wong, Wei Zheng, Nathaniel Rothman, Xiao Ou Shu, Qing Lan

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


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: p trend =0.05; Simpson: p trend =0.04; Observed Species: p trend =0.64). No case-control differences were apparent for beta diversity (p MiRKAT =0.30). After accounting for multiple comparisons, a greater abundance of Spirochaetia (OR low 1.00 (reference), OR medium 0.61 (95% CI 0.32 to 1.18), OR high 0.42 (95% CI 0.21 to 0.85)) and Bacteroidetes (OR low 1.00 (reference), OR medium 0.66 (95% CI 0.35 to 1.25), OR high 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 (OR low 1.00 (reference), OR medium 1.49 (95% CI 0.73 to 3.08), OR high 2.40 (95% CI 1.18 to 4.87)) and Lactobacillales order (OR low 1.00 (reference), OR medium 2.15 (95% CI 1.03 to 4.47), OR high 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.

Original languageEnglish (US)
Pages (from-to)256-263
Number of pages8
Issue number3
StatePublished - Mar 1 2021


  • lung cancer
  • non-small cell lung cancer

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine


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