Association Of Oral Microbiome With Lung Cancer Risk: Results From The Southern Community Cohort Study

Lung cancer is the leading cause of cancer death in the United States. The lungs are inhabited by diverse microbial communities. Bacterial infection in the lungs, such as a history of pneumonia and tuberculosis, has been associated with increased risk of lung cancer. Recent studies have found that the oral microbiome is the primary source of the bacterial microbiota in the lungs and that the bacterial species detected in the lungs overlap those found in the mouth. Therefore, readily-accessible oral samples may be used to investigate the role of bacteria in lung cancer etiology. In this study, we evaluated the association of the oral microbiome with subsequent risk of developing lung cancer. We conducted a nested case-control study using resources of the Southern Community Cohort Study, a well-characterized prospective cohort study of approximately 86,000 adult men and women, two-thirds of whom are African American. DNA was isolated from pre-diagnostic mouth rinse samples of 177 lung cancer cases and 177 controls matched on age, race, sex, smoking, and date of sample collection. The V4 domain of microbial 16S rRNA gene was sequenced. Sequencing libraries were prepared using the NEXTflex 16S V4 Amplicon-Seq Kit and sequenced with paired-end 150 bp using Illumina MiSeq. Sequencing data were processed using QIIME, and sequence reads were clustered into Operational Taxonomic Units (OTUs). On average, 82,254 sequencing reads were obtained for each sample. Duplicated quality control samples (n = 18; 2 samples each repeated for 9 times) showed very similar microbiome compositions, indicating high data quality. A total of 693 OTUs were observed and classified to 11 phyla. The observed composition was similar to the oral microbiome data from other studies, including the Human Microbiome Project. Multiple oral bacteria differed between lung cancer cases and controls. For example, Order CW040 was associated with increased lung cancer risk with OR of 3.64 (P = 0.0098). Family Tissierellaceae and Genus Parvimonas were associated with decreased risk of lung cancer with ORs of 0.42 (P = 0.0025) and 0.41 (P = 0.0014), respectively. Some of the associations differed by race. Among the lung cancer-associated oral bacteria, Family Fusobacteriaceae, Family Neisseriaceae, and Order Bacteroidales were among the most abundant bacteria found in the lungs. In summary, our study suggests that certain bacteria in the mouth are associated with substantial development of lung cancer and that the oral microbiome plays an important role in lung cancer etiology. Further studies with a larger sample size and with more comprehensive investigation are needed to confirm these findings. Citation Format: Qiuyin Cai, Jirong Long, Hua Xie, Xiaofei Wang, Jie Wu, Regina Courtney, Xiao Ou Shu, Wei Zheng, William J. Blot. Association of oral microbiome with lung cancer risk: Results from the Southern Community Cohort Study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3455.