Noncommunicable diseases (NCDs), of which cancer is second only to cardiovascular diseases, are on the rise and are considered the next disease frontier by the WHO. While colorectal cancer (CRC) is already a public health threat in the United States, there has been an unpredicted increase in the incidence of CRCs in Low- Middle Income Countries (LMICs). Unfortunately, only 1/5th of the world?s countries report national cancer incidence and mortality estimates, with the poorest quality data from less developed countries. However, the trends point to a likely increase in disease burden in low-income countries and the need for early detection and surveillance to halt the disparate mortality rates as 70% of all CRC-related deaths occur in LMICs. Nonetheless, CRC can be addressed through prevention when resources are available. At present, the invasiveness, expense and resources required for screening colonoscopy limit its utility globally in LMICs. The understanding of CRC incidence and prevalence is limited in Africa as is the potential linkage between causes of diarrheal disease and promotion of CRC. We are conducting diarrheal surveillance in Cameroon and Tanzania, where limited information exists regarding CRC, but where data highlight that CRC is found in a younger population (<50 years old) in Tanzania, which is comparable to rates reported by other sub-Saharan African countries. This mirrors the emergence of early age onset CRC in the United States, an alarming trend. The proposed study will conduct diarrheal surveillance for pro- and anti-carcinogenic bacteria in Tanzania and two regions of Cameroon: The Littoral Region (Douala) and the Far North Region. We will characterize the bacteria present using molecular methods. In Tanzania, we will additionally conduct clinical colonoscopy and CRC resection studies to compare colonization with pro- and anti-carcinogenic bacteria, biofilms (bfs) and bacterial communities using fecal and colonoscopy biopsy specimens as well as CRC resections. Thus, this proposal will describe the molecular epidemiology of pro- and anti-carcinogenic bacteria in two countries in Africa: Tanzania and Cameroon. Herein, we test the hypothesis that the pro- and anti-carcinogenic bacterial balance and/or biofilm formation are environmental features contributing to early onset CRC. These data will be invaluable in identifying key microbial features likely relevant to the pathogenesis of human CRC. Our results will help determine if the microbial features of CRC display common elements across diverse geographic and cultural settings. Collectively, we anticipate that our results will facilitate development of CRC prevention strategies that can reach LMICs.

Public Health Relevance

This collaboration between Johns Hopkins University (Drs. Sack, Sears & Debes), the University of Virginia (Drs. Houpt, Liu), a research organization in Tanzania, Kilimanjaro Christian Medical Center (KCMC), (Drs. Mmbanga and Ayesiga) and parent R01 research organization in Cameroon, Meilleur Accs aux Soins de Sant (M.A.Sante) (Dr. Ateudjieu) will characterize the microbiome associations of CRC in Tanzania and their potential linkage to diarrheal diseases in Tanzania and Cameroon. The pro:anti-carcinogenic balance of colon bacteria will be probed to determine if these biomarkers and/or other microbiome features may be useful for early detection and/or prevention of CRC in Africa.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
3R01AI123422-04S1
Application #
9971823
Study Section
Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
Hall, Robert H
Project Start
2017-04-01
Project End
2021-03-31
Budget Start
2020-04-01
Budget End
2021-03-31
Support Year
4
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
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Garrine, Marcelino; Mandomando, InĂ¡cio; Vubil, Delfino et al. (2017) Minimal genetic change in Vibrio cholerae in Mozambique over time: Multilocus variable number tandem repeat analysis and whole genome sequencing. PLoS Negl Trop Dis 11:e0005671
George, Christine Marie; Rashid, Mahamud; Almeida, Mathieu et al. (2017) Genetic relatedness of Vibrio cholerae isolates within and between households during outbreaks in Dhaka, Bangladesh. BMC Genomics 18:903