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The oral microbiome and lung cancer risk: An analysis of 3 prospective cohort studies.

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.