|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|
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.
Sex, body mass index, and dietary fiber intake influence the human gut microbiome.
Authors: Dominianni C, Sinha R, Goedert JJ, Pei Z, Yang L, Hayes RB, Ahn J
Source: PLoS One, 2015;10(4), p. e0124599.
EPub date: 2015 Apr 15.
Microbiome, innate immunity, and esophageal adenocarcinoma.
Authors: Baghdadi J, Chaudhary N, Pei Z, Yang L
Source: Clin Lab Med, 2014 Dec;34(4), p. 721-32.
EPub date: 2014 Sep 26.
The interrelationships of the gut microbiome and inflammation in colorectal carcinogenesis.
Authors: Cho M, Carter J, Harari S, Pei Z
Source: Clin Lab Med, 2014 Dec;34(4), p. 699-710.
EPub date: 2014 Sep 15.
Comparison of methods for fecal microbiome biospecimen collection.
Authors: Dominianni C, Wu J, Hayes RB, Ahn J
Source: BMC Microbiol, 2014 Apr 23;14, p. 103.
EPub date: 2014 Apr 23.
Human gut microbiome and risk for colorectal cancer.
Authors: Ahn J, Sinha R, Pei Z, Dominianni C, Wu J, Shi J, Goedert JJ, Hayes RB, Yang L
Source: J Natl Cancer Inst, 2013 Dec 18;105(24), p. 1907-11.
EPub date: 2013 Dec 6.
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 Nov 6.
Prospective study of the relationship between coffee and tea with colorectal cancer risk: the PLCO Cancer Screening Trial.
Authors: Dominianni C, Huang WY, Berndt S, Hayes RB, Ahn J
Source: Br J Cancer, 2013 Sep 3;109(5), p. 1352-9.
EPub date: 2013 Aug 1.
Diversity of 5S rRNA genes within individual prokaryotic genomes.
Authors: Pei A, Li H, Oberdorf WE, Alekseyenko AV, Parsons T, Yang L, Gerz EA, Lee P, Xiang C, Nossa CW, Pei Z
Source: FEMS Microbiol Lett, 2012 Oct;335(1), p. 11-8.
EPub date: 2012 Aug 2.