Albert Einstein College of Medicine, Bronx, New York, USA
Vanderbilt University, Nashville, Tennessee, USA.
Thorax. 2021 Mar;76(3):256-263. doi: 10.1136/thoraxjnl-2020-215542. Epub 2020 Dec 14.
To prospectively investigate whether diversity in oral microbiota is associated with risk of lung cancer among never-smokers.
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).
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).
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.
Subjects with lower microbiota alpha diversity had an increased risk of lung cancer compared with those with higher microbial alpha diversity (Shannon: p=0.05; Simpson: p=0.04; Observed Species: p=0.64). No case-control differences were apparent for beta diversity (p=0.30). After accounting for multiple comparisons, a greater abundance of Spirochaetia (OR 1.00 (reference), OR 0.61 (95% CI 0.32 to 1.18), OR 0.42 (95% CI 0.21 to 0.85)) and Bacteroidetes (OR 1.00 (reference), OR 0.66 (95% CI 0.35 to 1.25), OR 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 1.00 (reference), OR 1.49 (95% CI 0.73 to 3.08), OR 2.40 (95% CI 1.18 to 4.87)) and Lactobacillales order (OR 1.00 (reference), OR 2.15 (95% CI 1.03 to 4.47), OR 3.26 (95% CI 1.58 to 6.70)) was associated with an increased risk of lung cancer.
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.
前瞻性研究口腔微生物多样性与从不吸烟者肺癌风险之间的关系。
两项前瞻性队列研究中的巢式病例对照研究，上海妇女健康研究（n=74941）和上海男性健康研究（n=61480）。
在基线时无癌症的终身不吸烟者。病例是被诊断为肺癌（n=114）的患者，并按性别、年龄（≤2 岁）、日期（≤30 天）和样本采集时间（上午/下午）、样本采集前一周抗生素使用情况（是/否）和绝经状态（女性）与对照组 1:1 匹配。
使用宏基因组鸟枪法测序来测量每个病例和对照的预诊断口腔冲洗样本中的口腔微生物组的群落结构和丰度。多变量逻辑回归模型用于估计肺癌风险与 alpha 多样性指标和分类群相对丰度之间的关联。基于微生物组的核关联测试（MiRKAT）评估了风险与微生物组 beta 多样性之间的关联。
与微生物 alpha 多样性较高的患者相比，alpha 多样性较低的患者肺癌风险增加（香农：p=0.05；辛普森：p=0.04；观察到的物种：p=0.64）。beta 多样性无病例对照差异（p=0.30）。在考虑了多次比较后，螺旋体（OR 1.00（参考），OR 0.61（95%CI 0.32 至 1.18），OR 0.42（95%CI 0.21 至 0.85））和拟杆菌门（OR 1.00（参考），OR 0.66（95%CI 0.35 至 1.25），OR 0.31（95%CI 0.15 至 0.64））的丰度增加与肺癌风险降低相关，而芽孢杆菌纲（OR 1.00（参考），OR 1.49（95%CI 0.73 至 3.08），OR 2.40（95%CI 1.18 至 4.87））和乳杆菌目（OR 1.00（参考），OR 2.15（95%CI 1.03 至 4.47），OR 3.26（95%CI 1.58 至 6.70））的丰度增加与肺癌风险增加相关。
我们对从不吸烟者的前瞻性研究表明，alpha 多样性较低与肺癌风险增加相关，而某些特定分类群的丰度与风险改变相关，这为不吸烟的肺癌病因学提供了进一步的见解。
