Journal
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
Volume 114, Issue 11, Pages 1501-1510Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/jnci/djac149
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Funding
- Intramural Research Program of the National Institutes of Health, the National Institute of Environmental Health Sciences [Z01-ES049030]
- National Cancer Institute [Z01-CP010119]
- National Cancer Institute, National Institutes of Health [75N910D00024]
- National Cancer Institute Informatics Technology for Cancer Research Award [1U24CA248454-01]
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This study found prospective associations between oral microbiota and lung cancer risk in 3 US cohort studies, with variations based on smoking history and histological subtype.
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, 1306 incident lung cancer cases were identified in the Agricultural Health Study; National Institutes of Health-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 bioinforrnatics were conducted using QIIME 2. Hazard ratios and 95% confidence intervals were calculated using weighted Cox proportional hazards models. Results: Higher alpha diversity was associated with lower lung cancer risk (Shannon index hazard ratio = 0.90, 95% confidence interval = 0.84 to 0.96). Specific principal component vectors of the microbial communities were also statistically significantly associated with lung cancer risk. After multiple testing adjustment, greater relative abundance of 3 genera and presence of 1 genus were associated with greater lung cancer risk, whereas presence of 3 genera were associated with lower risk. For example, every SD increase in Streptococcus abundance was associated with 1.14 times the risk of lung cancer (95% confidence interval = 1.06 to 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 3 US cohort studies, with associations varying by smoking history and histologic subtype. The oral microbiome may offer new opportunities for lung cancer prevention.
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