Colorectal cancer (CRC) is a major cause of morbidity and mortality. It is a heterogeneous disease, with significant epidemiologic and biologic differences depending on the location of the cancer in the colon; specifically, whether the tumors are right-sided or left-sided. Factors that trigger tumorogenesis or contribute to differences in outcomes of this malignancy are poorly understood. Epidemiologic data indicate a higher incidence of right-sided cancers in females, African-Americans, and individuals over 70 years of age, and possibly a higher mortality for right-sided versus left-sided cancers. Differences are attributable to a number of genetic and non-genetic factors, including host genetic interactions, social determinants of health, such as health insurance status and access to screening, diet, and environmental triggers, as well as possible infectious agents. The detection of infectious agents in CRC tissue is increasingly important to establish associations and ultimately discover the pathogenic mechanisms behind this malignancy. Recent reports suggest that viruses, as well as certain bacteria, may be important determinants of CRC. However, the detection and characterization of viruses in CRC tissues has been hampered by the difficulty in culturing or isolating viruses by conventional molecular biology methods. In the proposed prospective pilot study, we seek to conduct comparative metagenomic and metabolomic analyses of healthy (n=50) versus tumorous tissues (n=50) from patients with right-sided versus left-sided CRC. All samples will be collected from patients undergoing curative resection at the Department of Surgery of the University of California, San Diego. We will determine the presence of distinct viral and microbial communities, biofilm layers, and metabolomic profiles in approximately 15 right-sided and 35 left-sided tumors and in the adjacent normal tissue (negative control). Comparative analyses between viral and microbial expression, molecular events and tumor location will be correlated. Metagenomics is a comprehensive technique for surveying microbial species associated with a disease, and combines the power of deep sequencing genomics, bioinformatics, and systems biology. It has been used to describe the microbial content of environmental and clinical samples. Preliminary work by members of our team investigating the CRC microbiome and metabolomic profiles revealed the differential presence of a microbial biofilm layer with a unique metabolomic profile on significantly more right-sided than left-sided cancers. Our group has been at the forefront of the development and application of the metagenomic approaches including the discovery of novel viruses. Combining these techniques with metabolomics profiling can lead to the discovery of novel viral and metabolic triggers of carcinogenesis in the colon.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
2U54CA132384-06A1
Application #
9043697
Study Section
Special Emphasis Panel (ZCA1-PCRB-C (O1))
Project Start
Project End
Budget Start
2015-09-01
Budget End
2016-08-31
Support Year
6
Fiscal Year
2015
Total Cost
$65,442
Indirect Cost
$21,814
Name
San Diego State University
Department
Type
DUNS #
073371346
City
San Diego
State
CA
Country
United States
Zip Code
92182
Perez, L G; Elder, J P; Haughton, J et al. (2018) Socio-demographic Moderators of Associations Between Psychological Factors and Latinas' Breast Cancer Screening Behaviors. J Immigr Minor Health 20:823-830
Tao, Li; Schwab, Richard B; San Miguel, Yazmin et al. (2018) Breast Cancer Mortality in Older and Younger Breast Cancer Patients in California. Cancer Epidemiol Biomarkers Prev :
Gude, Natalie A; Sussman, Mark A (2018) Chasing c-Kit through the heart: Taking a broader view. Pharmacol Res 127:110-115
Gude, Natalie A; Firouzi, Fareheh; Broughton, Kathleen M et al. (2018) Cardiac c-Kit Biology Revealed by Inducible Transgenesis. Circ Res 123:57-72
Yeoman, Benjamin Michael; Katira, Parag (2018) A stochastic algorithm for accurately predicting path persistence of cells migrating in 3D matrix environments. PLoS One 13:e0207216
Soto, Sandra H; Arredondo, Elva M; Haughton, Jessica et al. (2018) Leisure-Time Physical Activity and Characteristics of Social Network Support for Exercise Among Latinas. Am J Health Promot 32:432-439
Castañeda, Sheila F; Bharti, Balambal; Espinoza-Giacinto, Rebeca Aurora et al. (2018) Evaluating Two Evidence-Based Intervention Strategies to Promote CRC Screening Among Latino Adults in a Primary Care Setting. J Racial Ethn Health Disparities 5:530-535
Wells, Kristen J; Campbell, Kevin; Kumar, Ambuj et al. (2018) Effects of patient navigation on satisfaction with cancer care: a systematic review and meta-analysis. Support Care Cancer 26:1369-1382
Baik, Sharon H; Fox, Rina S; Mills, Sarah D et al. (2017) Reliability and validity of the Perceived Stress Scale-10 in Hispanic Americans with English or Spanish language preference. J Health Psychol :1359105316684938
Martínez, María Elena; Gomez, Scarlett L; Tao, Li et al. (2017) Contribution of clinical and socioeconomic factors to differences in breast cancer subtype and mortality between Hispanic and non-Hispanic white women. Breast Cancer Res Treat 166:185-193

Showing the most recent 10 out of 110 publications