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The microbiome as a risk factor and biomarker of oesophageal cancer

The microbiome is an environmental risk factor for several pathophysiologies. The microbiome on colorectal cancer (CRC) biopsies differs from that on mucosal biopsies of healthy controls. This altered microbiome could contribute to CRC through toxin production, DNA breakage, or driving inflammation leading to cancer. We recently identified microbiome differences between left and right sided cancers; CRC microbiota subtypes that correlated with host immune response; a polyp microbiota that was intermediate between CRC and controls. Two of the CRC microbiota subtypes include oral bacteria. In a pilot study, we could distinguish CRC patients from controls based on their oral microbiome. We hypothesize that oral bacteria may seed the altered microbiome on gut cancers. This has important implications for oesophageal adenocarcinoma (OAC). OAC is a multifactorial disease, the end result of a complicated relationship between genetics, immunity, environment, diet and lifestyle, all of which could interact bi-directionally with the microbiome. OAC is a model of an inflammation-associated cancer, and the microbiome may be pivotal in chronic inflammation i.e. reflux oesophagitis.
This Prospective Study will explore the oral and oesophageal microbiome associated with OAC and its precancerous and inflammatory states. We will recruit 40 subjects from each of 5 groups:
1. Normal oesophageal mucosa
2. Reflux oesophagitis
3. Barrett’s oesophagus
4. Barrett’s oesophagus with low and high grade dysplasia and T1a adenocarcinoma
5. Locally advanced but resectable OAC
We will determine the microbiota composition of five biopsies plus the oral cavity per patient. We will analyze expression of selected innate immunity genes by qRT-PCR. The microbiota data will be compared to clinical metadata (adjusting for diet and lifestyle risk factors) and immune response to identify microbiota signatures or bacterial taxa that correlate with disease state and pathology, and to test if the oral microbiota can predict oesophageal abnormalities ranging from inflammation to cancer.