Genomic Instability, Race, and Immune Relationships in Colorectal Cancer

 

SDSU Co-Leader

Kathleen L. McGuire, Ph.D.

UCSD Co-Leader

John M. Carethers, M.D.

 

ABSTRACT

Colorectal cancer is common in the United States and a key risk factor for development includes race, with Blacks having the highest incidence and death rates. It is not clear what causes this disparity. In preliminary data, we have shown that one form of genomic instability leading to the formation of colorectal cancers, called microsatellite instability (MSI), is prevalent among Blacks with colon cancer 50% less than in Whites with colon cancer. This is significant because MSI tumors are less aggressive and the patients with MSI tumors have better survival than individuals with other kinds of colon cancer. Whether the lower incidence of MSI tumors in Blacks is enough to account for the racial disparity observed in colorectal cancer is not yet clear. However, we believe that it will be only one of the biological differences that lead to more aggressive tumors and higher death rates in Black Americans. It is now clear that the immune response is very important in the progression of colorectal cancer, and we are also investigating how it might influence the diseases and play a role in the racial disparities observed.

Project Period: 9/1/2008 – 8/31/2012

Selected Outcomes

 

Publications

Carethers JM. Proteomics, genomics and molecular biology in the personalized treatment of colorectal cancer. J Gastrointest Surg, 2012. (in press)

Chung H, Chaudhry J, Lai JF, Young DJ, Carethers JM. Flanking nucleotide specificity for DNA mismatch repair-deficient frameshifts within Activin Receptor 2 (ACVR2). Mutat Res, 729:73-80, 2012.

Lee S-Y, Miyai K, Han HS, Hwang D-Y, Seong MK, Chung H, Jung BH, Devaraj B, McGuire KL, Carethers JM. Microsatellite instability, EMAST, and morphology associations with T cell infiltration in colorectal neoplasia. Dig Dis Sci 57:72-78, 2012.

Carethers JM. Changing concepts of MSI in colorectal cancer. Gut and Liver 5(3; Suppl. 1):21-23, 2011.

Carethers JM. One colon lumen but two organs. Gastroenterology, 141:411-412, 2011.

Funded Grants

NIH/NCI U01-CA162147 (PI: John M. Carethers; subcontract: Kathie L. McGuire)

NIH/NCI 1 R01CA137873 (PI: John M. Carethers)

Presentations

Basa, RCB, X Li, B Murali, B Yang, M Lee, R Janke, M Ji, T Ngo, R Tejada, R Alfaro, JM Carethers, KL McGuire. Cytotoxic Immune responses in colorectal cancer. CSU Program for Education and Research in Biotechnology Annual Symposium, 2012

Davies, V, R Tejada, R Alfaro, A Washington Jr., M. Kinseth, KL McGuire. Pro and anti-tumor immune responses within a mouse model of colorectal cancer. CSU Program for Education and Research in Biotechnology Annual Symposium, 2012

Li, X, B Murali, B Yang, RCB Basa, M Kinseth, JM Carethers, KL McGuire. Differences in granzyme B expression may contribute to racial disparities in colorectal cancer. Student Research Symposium, San Diego State University, 2012.

Carethers JM. Invited Speaker, SDSU Department of Biology, “Changing concepts of MSI in colorectal cancer”. June 25, 2012.

Carethers JM Keynote Speaker, University of Maryland Division of Gastroenterology T32 Grant, “Changing concepts of MSI in colorectal cancer”, June 14, 2012

Carethers JM Invited Speaker, “Gastrointestinal carcinogenesis: novel approaches to therapeutic intervention”, AGA Spring Postgraduate Course, San Diego, CA, May 19, 2012

Carethers JM Visiting Professor, Tufts Division of Gastroenterology Grand Rounds, “Changing concepts of MSI in colorectal cancer”, May 3, 2012

Carethers JM Edward S. Cooper Visiting Professor of Medicine, “Racial and ethnic considerations in colon cancer”, University of Pennsylvania Department of Medicine, April 17, 2012

Carethers JM Visiting Professor, UCSD Department of Medicine Grand Rounds, “Colorectal Cancer: Site, Race and Treatment Considerations”, March 28, 2012

Carethers JM John Lindenbaum Memorial Lecture and Visiting Professor “Racial and ethnic considerations in colon cancer”, Columbia University Medical Center, February 8, 2012.

Carethers JM Visiting Professor, Duke Division of Gastroenterology Grand Rounds, “Changing concepts of MSI in colorectal cancer”, January 19, 2012

Carethers JM MLK Distinguished Visiting Professor, Duke Department of Medicine Grand Rounds, “Racial and ethnic considerations in colon cancer”, January 20, 2012

Carethers JM Invited Speaker, St. John’s Hospital & Medical Center Grand Rounds, “Racial and ethnic considerations in colon cancer”, Detroit, MI, December 6, 2011