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Oral Microbiome Influences Risk of Esophageal Cancer Development

NEW YORK (GenomeWeb) – Some bacteria found in the mouth that contribute to periodontal disease are also linked to an increased risk of developing esophageal cancer, a new microbiome study has found.

Oral microbes have been linked to periodontal disease as well as to head and neck cancer. As such, researchers led by New York University School of Medicine's Jiyoung Ahn examined whether they were also associated with the development of esophageal cancer, the eighth most common cancer.

In a prospective case-control study, the researchers collected oral wash samples from 122,000 people, about a hundred of whom developed either esophageal adenocarcinoma or esophageal squamous cell carcinoma. As they reported in Cancer Research today, Ahn and her colleagues found that higher levels of bacteria like Tannerella forsythia and Porphyromonas gingivalis were associated with increased disease risk, while higher amounts of other bacteria like Neisseria appeared to protect against disease. 

"Our study indicates that learning more about the role of oral microbiota may potentially lead to strategies to prevent esophageal cancer, or at least to identify it at earlier stages," Ahn said in a statement.

For their study, the researchers drew on participants from the National Cancer Institute Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial and the American Cancer Society Cancer Prevention Study II Nutrition cohorts. Oral wash samples were collected from participants of both studies, and the participants were asked about their risk factors for esophageal cancer, which include smoking, drinking, and obesity, among others.

In 10 years of follow-up, 106 participants developed either esophageal adenocarcinoma or esophageal squamous cell carcinoma.

The researchers extracted DNA from mouthwash samples for 16S rRNA sequencing analysis from participants who developed cancer and matched controls who did not. They clustered the reads they generated into operational taxonomic units against the Human Oral Microbiome Database reference set.

The esophageal adenocarcinoma or esophageal squamous cell carcinoma cases didn't differ from controls in microbial species diversity or overall composition, the researchers noted.

Ahn and her colleagues were particularly interested in whether members of the so-called "red complex" — bacteria associated with periodontal disease including T. forsythia, P. gingivalis, and Treponema denticola — were also linked to esophageal cancer.

T. forsythia was particularly associated with an increased risk of cancer as higher oral levels of it was linked to a 21 percent increased risk of esophageal adenocarcinoma, the researchers reported. Increased numbers of P. gingivalis, meanwhile, was marginally linked to an increased risk of esophageal squamous cell carcinoma.

Other bacteria like Actinomyces cardiffensis, Selenomonas oral taxon 134, and Veillonella oral taxon 917 were also associated with rises in esophageal cancer risk.

At the same time, higher amounts of other bacteria appeared to decrease cancer risk. In particular, Ahn and her colleagues noted that Corynebacterium durum, Streptococcus pneumoniae, Neisseria sicca, and Neisseria flavescens, among others, were associated with a decreased risk of esophageal adenocarcinoma. Many of these species, the researchers noted, were connected to one another in an ecological network analysis.

The researchers noted that this inverse association between Streptococcus pneumonia and disease was consistent with previous findings, but that the inverse association of Neisseria anddisease was contrary to previous studies, which found it to be increased in esophageal cancer patients.

Still, Ahn and her colleagues said that their findings suggested that potentially protective bacteria, including Neisseria, should be examined further to see if they do help modulate or prevent esophageal cancer.

The researchers cautioned that while their study is the largest of its kind to date, the number of cases it examined was small.

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