Our hypothesis is that gut microbiome profiles are associated with risk of colorectal cancer. Altered gut microbiome may promote colorectal carcinogenesis by inducing chronic inflammation. Also, gut microbiota may be related to CRC risk by metabolizing food components, such as carcinogenic heterocyclic amines. However, past studies of microbial flora and colorectal cancer are limited to animal models and small human studies, both considering only a selected number of culturable microbial species. To our knowledge, no epidemiologic study has comprehensively evaluated the relationship of the human gut microbiome to risk of colorectal cancer using gene sequence-based approach. We propose an innovative study to comprehensively examine the relationship between gut microbiome profile and colorectal cancer risk in a case-control study (69 cases and 114 controls), with previously collected and lyophilized fecal biospecimens obtained before initiation of any treatment, in study samples collected by NCI with associated demographic and clinical information (Schiffman MH et al, Cancer Research, 1989). We will comprehensively survey common gut microbial species (including non-culturables) from fecal biospecimens by sequencing of the 16S rRNA microbial genes. We will 1) define the normal gut microbiome in the control group, and 2) examine if the gut microbiome differs between colorectal cancer cases and controls. As a secondary aim, we will evaluate intra-individual variability (temporal stability of gut microbiome profile collected at study recruitment and after 6 months in a subset of 20 randomly selected individuals from the control group. This project is timely and highly relevant to the goals of the NIH Roadmap and the NIH Human Microbiome Project (HMP). Results from this first comprehensive evaluation of the gut microbiome will identify colorectal cancer-related gut bacterial profiles and improve our understanding of the etiology of this disease. Understanding the temporal stability of the microbiome profile in this R03 grant will lay the foundation for subsequent R01 applications, proposing large-scale prospective evaluation with fecal biospecimen collection. Considering the significant public health burden of colorectal cancer as the second leading cause of cancer death in the US, and the potential importance of the microbiome in its causation, there is great need for the proposed R03 study.

Public Health Relevance

More than 160,000 cases of colorectalcancer are diagnosed annually in the US, and 57,000 patients die of the disease, making it the second leading cause of death from cancer among adults. We will determine the impact of microbes in the gut on risk for these diseases. Our study will identifying gut bacterial profiles related to colorectal cancer risk, providing direct leads to implement microbial prophylactic interventions.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Research Grants (R03)
Project #
1R03CA159414-01A1
Application #
8241555
Study Section
Special Emphasis Panel (ZCA1-SRLB-D (O1))
Program Officer
Starks, Vaurice
Project Start
2012-03-01
Project End
2014-02-28
Budget Start
2012-03-01
Budget End
2013-02-28
Support Year
1
Fiscal Year
2012
Total Cost
$84,500
Indirect Cost
$34,500
Name
New York University
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
Fan, Xiaozhou; Peters, Brandilyn A; Jacobs, Eric J et al. (2018) Drinking alcohol is associated with variation in the human oral microbiome in a large study of American adults. Microbiome 6:59
Sinha, Rashmi; Goedert, James J; Vogtmann, Emily et al. (2018) Quantification of Human Microbiome Stability Over 6 Months: Implications for Epidemiologic Studies. Am J Epidemiol 187:1282-1290
Fan, Xiaozhou; Alekseyenko, Alexander V; Wu, Jing et al. (2018) Human oral microbiome and prospective risk for pancreatic cancer: a population-based nested case-control study. Gut 67:120-127
Peters, Brandilyn A; Wu, Jing; Pei, Zhiheng et al. (2017) Oral Microbiome Composition Reflects Prospective Risk for Esophageal Cancers. Cancer Res 77:6777-6787
Peters, Brandilyn A; Wu, Jing; Hayes, Richard B et al. (2017) The oral fungal mycobiome: characteristics and relation to periodontitis in a pilot study. BMC Microbiol 17:157
Peters, Brandilyn A; Dominianni, Christine; Shapiro, Jean A et al. (2016) The gut microbiota in conventional and serrated precursors of colorectal cancer. Microbiome 4:69
Sinha, Rashmi; Ahn, Jiyoung; Sampson, Joshua N et al. (2016) Fecal Microbiota, Fecal Metabolome, and Colorectal Cancer Interrelations. PLoS One 11:e0152126
Wu, Jing; Peters, Brandilyn A; Dominianni, Christine et al. (2016) Cigarette smoking and the oral microbiome in a large study of American adults. ISME J 10:2435-46
Neto, Antonio Galvao; Whitaker, April; Pei, Zhiheng (2016) Microbiome and potential targets for chemoprevention of esophageal adenocarcinoma. Semin Oncol 43:86-96
Yang, Liying; Poles, Michael A; Fisch, Gene S et al. (2016) HIV-induced immunosuppression is associated with colonization of the proximal gut by environmental bacteria. AIDS 30:19-29

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