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National Institutes of Health: National Cancer Institute: Division of Cancer Control and Population Sciences
Grant Details

Grant Number: 1R03CA159414-01A1 Interpret this number
Primary Investigator: Ahn, Jiyoung
Organization: New York University School Of Medicine
Project Title: Gut Microbiome Profiles and Risk of Colorectal Cancer
Fiscal Year: 2012
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Abstract

DESCRIPTION (provided by applicant): 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.

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Publications

Cigarette smoking and the oral microbiome in a large study of American adults.
Authors: Wu J. , Peters B.A. , Dominianni C. , Zhang Y. , Pei Z. , Yang L. , Ma Y. , Purdue M.P. , Jacobs E.J. , Gapstur S.M. , et al. .
Source: The ISME journal, 2016-03-25; , .
EPub date: 2016-3-25.
PMID: 27015003
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Microbiome and potential targets for chemoprevention of esophageal adenocarcinoma.
Authors: Neto A.G. , Whitaker A. , Pei Z. .
Source: Seminars in oncology, 2016 Feb; 43(1), p. 86-96.
EPub date: 2015-09-07.
PMID: 26970127
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HIV-induced immunosuppression is associated with colonization of the proximal gut by environmental bacteria.
Authors: Yang L. , Poles M.A. , Fisch G.S. , Ma Y. , Nossa C. , Phelan J.A. , Pei Z. .
Source: AIDS (London, England), 2016-01-02; 30(1), p. 19-29.
PMID: 26731752
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Microbiome, a new dimension in cancer research.
Authors: Neto A.G. , Bradshaw A.D. , Pei Z. .
Source: Annals of translational medicine, 2015 Sep; 3(16), p. 229.
PMID: 26539446
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Fast disease progression in simian HIV-infected female macaque is accompanied by a robust local inflammatory innate immune and microbial response.
Authors: Ren W. , Ma Y. , Yang L. , Gettie A. , Salas J. , Russell K. , Blanchard J. , Davidow A. , Pei Z. , Chang T.L. , et al. .
Source: AIDS (London, England), 2015-06-19; 29(10), p. F1-8.
PMID: 26035329
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Sex, body mass index, and dietary fiber intake influence the human gut microbiome.
Authors: Dominianni C. , Sinha R. , Goedert J.J. , Pei Z. , Yang L. , Hayes R.B. , Ahn J. .
Source: PloS one, 2015; 10(4), p. e0124599.
EPub date: 2015-04-15.
PMID: 25874569
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Microbiome, innate immunity, and esophageal adenocarcinoma.
Authors: Baghdadi J. , Chaudhary N. , Pei Z. , Yang L. .
Source: Clinics in laboratory medicine, 2014 Dec; 34(4), p. 721-32.
EPub date: 2014-09-26.
PMID: 25439272
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The interrelationships of the gut microbiome and inflammation in colorectal carcinogenesis.
Authors: Cho M. , Carter J. , Harari S. , Pei Z. .
Source: Clinics in laboratory medicine, 2014 Dec; 34(4), p. 699-710.
EPub date: 2014-09-15.
PMID: 25439270
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Comparison of methods for fecal microbiome biospecimen collection.
Authors: Dominianni C. , Wu J. , Hayes R.B. , Ahn J. .
Source: BMC microbiology, 2014; 14, p. 103.
EPub date: 2014-04-23.
PMID: 24758293
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Human gut microbiome and risk for colorectal cancer.
Authors: Ahn J. , Sinha R. , Pei Z. , Dominianni C. , Wu J. , Shi J. , Goedert J.J. , Hayes R.B. , Yang L. .
Source: Journal of the National Cancer Institute, 2013-12-18; 105(24), p. 1907-11.
EPub date: 2013-12-06.
PMID: 24316595
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Diversified microbiota of meconium is affected by maternal diabetes status.
Authors: Hu J. , Nomura Y. , Bashir A. , Fernandez-Hernandez H. , Itzkowitz S. , Pei Z. , Stone J. , Loudon H. , Peter I. .
Source: PloS one, 2013; 8(11), p. e78257.
EPub date: 2013-11-06.
PMID: 24223144
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Prospective study of the relationship between coffee and tea with colorectal cancer risk: the PLCO Cancer Screening Trial.
Authors: Dominianni C. , Huang W.Y. , Berndt S. , Hayes R.B. , Ahn J. .
Source: British journal of cancer, 2013-09-03; 109(5), p. 1352-9.
EPub date: 2013-08-01.
PMID: 23907431
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Diversity of 5S rRNA genes within individual prokaryotic genomes.
Authors: Pei A. , Li H. , Oberdorf W.E. , Alekseyenko A.V. , Parsons T. , Yang L. , Gerz E.A. , Lee P. , Xiang C. , Nossa C.W. , et al. .
Source: FEMS microbiology letters, 2012 Oct; 335(1), p. 11-8.
EPub date: 2012-08-02.
PMID: 22765222
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