Abstract 4961: The oral microbiome and prospective risk for esophageal cancer: A population-based nested case-control study
Authors: Peters Brandilyn A. , Wu Jing , Pei Zhiheng , Yang Liying , Purdue Mark P. , Freedman Neal D. , Jacobs Eric J. , Gapstur Susan M. , Hayes Richard B. , Ahn Jiyoung 
Published: July 2017

Background: The two most common types of esophageal cancer, esophageal adenocarcinoma (EAC) and squamous cell carcinoma (ESCC), are highly fatal. The human microbiota have been suggested to play a role in esophageal cancer etiology, although the evidence is limited to small, cross-sectional studies. We hypothesized that the oral microbiota, which shape the esophageal microbiota, may be causative agents in esophageal carcinogenesis.

Methods: We conducted a prospective study nested in two large U.S. cohorts: ACS CPS-II and NCI-PLCO. Oral bacteria were assessed in pre-diagnostic mouth-wash samples collected from cases and controls (n=81/160 EAC and n=25/50 ESCC cases/matched controls), using 16S rRNA gene sequencing. We compared overall microbial composition between cases and controls using permutational multivariate analysis of variance (PERMANOVA) of UniFrac distances, and we examined associations between centered log-ratio transformed taxon abundances and cancer risk using conditional logistic regression. Metagenome functional content was predicted from taxonomic composition using PiCRUST.

Results: Overall microbial composition did not differ between EAC cases and matched controls or ESCC cases and matched controls, adjusting for matching factors (age, sex, race, cohort, time to diagnosis/selection), BMI, smoking, and alcohol intake (all p&gt;0.40). The periodontal pathogens Tannerella forsythia and Porphyromonas gingivalis were nominally associated with increased risk for EAC (OR [95% CI] = 1.21 [1.01, 1.46], p=0.04) and ESCC (OR [95% CI] = 1.3 [0.96, 1.77], p=0.09), respectively. Conversely, genus Neisseria, previously shown to be depleted by cigarette smoking, was associated with protection against EAC (OR [95% CI] = 0.88 [0.8, 0.97], p=0.01). Other species associated with EAC risk (p&lt;0.05) included Corynebacterium durum, Prevotella nanceiensis, and Streptococcus pneumoniae (inversely associated with EAC), and Actinomyces cardiffensis, Selenomonas oral taxon 134, and Veillonella oral taxon 917 (positively associated with EAC). Other species associated with ESCC risk (p&lt;0.05) included Aggregatibacter paraphrophilus (inversely associated with ESCC) and Prevotella nanceiensis, Bergeyella oral taxon 322, and Neisseria weaveri (positively associated with ESCC). Analysis of inferred metagenomes revealed that bacterial carotenoid biosynthesis was associated with protection against EAC (OR [95% CI] = 0.84 [0.7, 1.0], p=0.05).

Conclusions: Our findings from this prospective study suggest that specific bacterial pathogens may play a causal role in esophageal cancer, while members of the healthy oral microbiota may protect against carcinogenesis. Unique microbial profiles may contribute to each of the distinct esophageal cancer types, EAC and ESCC. Oral microbiota manipulation may be a future strategy for preventing this highly fatal disease.

Citation Format: Brandilyn A. Peters, Jing Wu, Zhiheng Pei, Liying Yang, Mark P. Purdue, Neal D. Freedman, Eric J. Jacobs, Susan M. Gapstur, Richard B. Hayes, Jiyoung Ahn. The oral microbiome and prospective risk for esophageal cancer: A population-based nested case-control study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4961. doi:10.1158/1538-7445.AM2017-4961