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Case-cohort of oral microbiome and cancer risk

Principal Investigator
Name
Emily Vogtmann
Degrees
-
Institution
NCI
Position Title
-
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
2014-0191
Initial CDAS Request Approval
Feb 10, 2016
Title
Case-cohort of oral microbiome and cancer risk
Summary
Poor oral health and periodontal pathogens have been associated with a number of cancers, mortality, and other chronic diseases, which suggests that the oral microbiome likely plays a role in the development of these conditions. Oral bacteria may alter cancer risk through multiple mechanisms including local and systemic inflammation and metabolic activation of carcinogens from food, tobacco, alcohol, and other sources. We propose to assess the association between the oral microbiome and incident cancers of the bronchus/lung, colorectum, hepatobiliary tract, small intestine and stomach using a case-cohort design and samples from three other cohorts (Agricultural Health Study, Shanghai Women’s Health Study, and NIH-AARP Diet and Health Study). Several cancer sites of interest have low frequencies in each cohort, so we aim to combine these data to increase power. We will extract DNA and sequence the V4 region of the 16S rRNA gene from the oral rinse samples and calculate measures of alpha (microbial community complexity) and beta (microbial community relatedness based on taxonomy) diversity. Microbiome characterization technology is relatively new for epidemiologic studies, therefore, we are leading a multi-site quality control experiment to optimize DNA extraction, DNA sequencing, and bioinformatics (www.mbqc.org), which has given us insight into best practices. To minimize variability in data across the four cohorts we aim to complete sample and data handling steps in concert such that all DNA is extracted in a single laboratory (DESL, DCEG), sequenced at a single laboratory (Dr. Rob Knight, University of Colorado), and analyzed by our team (DCEG). The multi-cancer, multi-cohort project will allow us to test several hypotheses simultaneously using the best current technology and allow greater insight into the role of the oral microbiome in cancer at several sites and will allow us to evaluate common mechanisms for different cancer sites.
Aims

We aim to prospectively examine the association between the oral microbiota communities and the risk of five incident cancers that have not been previously examined in the PLCO (bronchus/lung, colorectum, hepatobiliary system, small intestine and stomach) as part of a multi-cohort study. We hypothesize that specific taxa will be associated with cancer risk and this study will be the first large-scale, multi-site prospective study of the oral microbiome and incident cancer. Future work could be conducted using the data generated from this study including studies of the associations with mortality, cardiovascular disease, diabetes, and chronic disease risk factors, such as, obesity.

Collaborators

Christian Abnet (Nutritional Epidemiology Branch)
Rashmi Sinha (Nutritional Epidemiology Branch)
Mitch Gail (Biostatistics Branch)
Neil Caporaso (Genetic Epidemiology Branch)
Emily Vogtmann (NCI)
Yukiko Yano (NCI)

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