Variation in the Oral Microbiome Is Associated With Future Risk of Lung Cancer Among Never-Smokers
abstract
This abstract is available on the publisher's site.
Access this abstract nowOBJECTIVE
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.
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Additional Info
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Variation in Oral Microbiome Is Associated With Future Risk of Lung Cancer Among Never-Smokers
Thorax 2020 Dec 14;[EPub Ahead of Print], HD Hosgood, Q Cai, X Hua, J Long, J Shi, Y Wan, Y Yang, C Abnet, BA Bassig, W Hu, BT Ji, M Klugman, Y Xiang, YT Gao, JY Wong, W Zheng, N Rothman, XO Shu, Q LanFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Active tobacco smoking is attributed to a majority of lung cancer incidence; however, 25% of lung cancer incidence is non–smoking related. Lung cancer in never-smokers is the seventh leading cause of cancer deaths globally. Therefore, there is a critical need to identify potential risk indicators and biomarkers that would aid in early diagnosis, better treatment outcomes, and increased survival rates. Several external, environmental, and biological factors are being investigated to be potential biomarkers or risk indicators. In this prospective nested case–control study using the largest never-smoker lung cancer patient cohort, Hosgood et al evaluate the role of the oral microbiome as a future risk predictor for lung cancer.
With the evolution of the human microbiome project, the effect of the bacterial communities (microbiome) in human physiology and their roles in health and disease has been gaining significance. Increased abundances of specific bacterial community members and decreases in particular beneficial (aka, commensal) bacterial species have been associated with several oral and systemic diseases. A decrease in bacterial diversity coupled with increased abundance of bacterial classes Bacilli and Lactobacillales was associated with increased lung cancer risk in never-smokers. An increase in bacterial diversity and increased abundance of Spirochaetia and Bacteroidetes were associated with decreased lung cancer risk. These results from this robustly designed clinical study are promising and pave the way for future investigations to determine the molecular underpinnings behind these associations. A future study with a larger cohort and a higher resolution at the species/strain level is warranted to identify the precise mechanisms underlying the associations between the specific bacterial members and changes in the environment leading to disease and, additionally, to validate the role of the microbiome as a risk indicator.