The microbiome refers to the collection of all of the gene sequences from a community of microbes in the human body. High-throughput DNA amplification and sequencing technologies to characterize the microbial communities provide data for investigations of microbial associations with human disease. Our goal is to create and use established and new cohorts with fecal and oral specimens to prospectively evaluate the association between the human microbiome and cancer risk.
While microbiome research has grown exponentially over the past several years, findings have been difficult to reproduce across studies. The variability induced by sample collection and handling has not been systematically assessed. Therefore, in addition to etiologic studies, DCEG investigators are pursuing a multi-pronged approach to address microbiome methodologic issues to validate optimal collection, storage, and analysis and to understand how to best interpret the complex data.
Etiologic Studies
Prospective study of the oral microbiome and mortality and cancer: Poor oral health and hygiene have been associated with a number of cancers, mortality, and other chronic diseases, which suggests a role for the oral microbiome in the development of these conditions, but few studies have examined direct measures of the bacteria. DCEG investigators are assessing the association between the oral microbiome and incident cancers of the bronchus/lung, colorectum, esophagus, head/neck, hepatobiliary tract, pancreas, small intestine and stomach, and all-cause mortality, using a case-cohort design within the Agricultural Health Study, the NIH-AARP Diet and Health Study, and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). This multi-cancer, multi-cohort project allows us to test several hypotheses simultaneously, provide greater insight into the role of the oral microbiome in cancer at several sites, and to investigate cross-sectional associations with various exposures such as diet, body mass index, and smoking.
Lower gastrointestinal cancer studies: The association between the human gut microbiome and colorectal cancer is an important focus of our research. We conduct 16S ribosomal gene sequencing and shotgun sequencing for microbiome analyses of the colorectum using fecal samples as well as tissue samples. We also evaluate microbial metabolites in the blood and fecal samples.
Upper gastrointestinal cancer studies: Gastric cancer is currently the model of bacterially associated cancer; Helicobacter pylori (H. pylori) has been classified as a Group 1 carcinogen in humans by the International Agency for Research on Cancer, indicating agents with the highest level of epidemiologic and mechanistic evidence. Research within DCEG has evaluated how risk factors for cancer, such as tobacco, body mass index, and pepsinogen levels, are associated with microbial diversity using samples collected in China. We have tested multiple methods for collecting tissue microbiome in the upper GI tract and explored the microbiome of tumors and adjacent normal tissue. New studies will explore how H. pylori and other upper GI carcinogens alter the gastric and esophageal tissue microbiome, whether the tumor microbiome can provide diagnostic or prognostic information for upper GI cancers, and will evaluate associations between the oral microbiome and upper gastrointestinal cancer risk in prospective studies.
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