Background Previous studies suggested associations between the oral microbiome and lung cancer, but studies were predominantly cross-sectional and underpowered. Methods Using a case-cohort design, 1,306 incident lung cancer cases were identified in the Agricultural Health Study, NIH-AARP Diet and Health Study, and Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Referent subcohorts were randomly selected by strata of age, sex, and smoking history. DNA was extracted from oral wash specimens using the DSP DNA Virus Pathogen kit, the 16S rRNA gene V4 region was amplified and sequenced, and bioinformatics were conducted using QIIME 2. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using weighted Cox proportional hazards models. Results Higher alpha diversity was associated with lower lung cancer risk (Shannon index HR 0.90; 95% CI: 0.84–0.96). Specific principal component vectors of the microbial communities were also significantly associated with lung cancer risk. After multiple testing adjustment, greater relative abundance of three genera and presence of one genus were associated with greater lung cancer risk, while presence of three genera were associated with lower risk. For example, every standard deviation increase in Streptococcus abundance was associated with 1.14 times the risk of lung cancer (95% CI: 1.06–1.22). Associations were strongest among squamous cell carcinoma cases and former smokers. Conclusions Multiple oral microbial measures were prospectively associated with lung cancer risk in three US cohort studies with associations varying by smoking history and histologic subtype. The oral microbiome may offer new opportunities for lung cancer prevention.

中文翻译：

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口腔微生物组和肺癌风险：对 3 项前瞻性队列研究的分析

背景 先前的研究表明口腔微生物组与肺癌之间存在关联，但研究主要是横断面研究且功效不足。方法 使用病例队列设计，在农业健康研究、NIH-AARP 饮食与健康研究以及前列腺癌、肺癌、结直肠癌和卵巢癌筛查试验中确定了 1,306 例肺癌病例。参考亚组是根据年龄、性别和吸烟史的层次随机选择的。使用DSP DNA Virus Pathogen试剂盒从口腔清洗标本中提取DNA，对16S rRNA基因V4区进行扩增和测序，并使用QIIME 2进行生物信息学分析。使用QIIME 2计算风险比（HR）和95%置信区间（CI）加权 Cox 比例风险模型。结果 较高的 alpha 多样性与较低的肺癌风险相关（香农指数 HR 0.90；95% CI：0.84–0.96）。微生物群落的特定主成分载体也与肺癌风险显着相关。经过多次检验调整后，三个属的相对丰度较高和一个属的存在与肺癌风险较高相关，而三个属的存在与风险较低相关。例如，链球菌丰度每增加一个标准差，肺癌风险就会增加 1.14 倍（95% CI：1.06–1.22）。鳞状细胞癌病例和前吸烟者之间的关联最强。结论 在美国的三项队列研究中，多种口腔微生物指标与肺癌风险前瞻性相关，相关性因吸烟史和组织学亚型而异。口腔微生物组可能为肺癌预防提供新的机会。