Abstract CN10-04: Profiling of tumors to identify factors that contribute to cancer health disparities

Not all segments of the U.S. population have equally benefited from the advances in our knowledge and treatment of cancer. As a result, African Americans still have the highest prostate and breast cancer mortalities among all U.S. racial and ethnic groups. Recent research showed that these disparities in prostate and breast cancer survival between African American (AA) and European American (EA) patients persist in randomized clinical trials (1), suggesting that intrinsic differences in tumor biology may contribute to the survival differences between these two patient cohorts. Moreover, AA breast cancer patients represent more frequently than EA patients with a high grade and ER-negative disease, and the aggressive basal-like and triple-negative breast cancer subtypes are more common among them than women from other population groups. This pattern is reminiscent of disease presentation in West Africa (2), indicating that women of West African ancestry tend to develop a different tumor biology than women of European descent. In two pilot studies, we examined the tumor biology of prostate and breast cancer comparing AA patients with EA patients using large scale gene expression profiling and found significant differences in gene expression that are consistent with race/ethnic differences in the tumor microenvironment and immunobiology (3, 4). Intriguingly, a prominent interferon gene signature was detected in AA prostate and breast tumors that may relate to an unknown etiologic agent in disease pathology, or to certain genomic alterations in the cancer cells. This signature may also influence therapeutic outcome because it has great homology with a recently discovered interferon-related DNA damage resistance signature, which predicts resistance to chemotherapy and radiation in breast cancer and perhaps other epithelial cancers (5, 6). Quite unexpected, this same interferon signature can also be induced by tumor-stroma interactions (7). Future research should examine whether the interferon-related DNA damage resistance signature is prevalent in tumors of AA patients and patients from West Africa, and how it influences the response to therapy. References: 1. Albain,K.S., Unger,J.M., Crowley,J.J., Coltman,C.A., Jr. and Hershman,D.L. Racial disparities in cancer survival among randomized clinical trials patients of the Southwest Oncology Group, J Natl Cancer Institute, 101: 984-992, 2009. 2. Huo,D., Ikpatt,F., Khramtsov,A., Dangou,J.M., Nanda,R., Dignam,J., Zhang,B., Grushko,T., Zhang,C., Oluwasola,O., Malaka,D., Malami,S., Odetunde,A., Adeoye,A.O., Iyare,F., Falusi,A., Perou,C.M. and Olopade,O.I. Population Differences in Breast Cancer: Survey in Indigenous African Women Reveals Over-Representation of Triple-Negative Breast Cancer, J Clin Oncol., 2009. 3. Wallace,T.A., Prueitt,R.L., Yi,M., Howe,T.M., Gillespie,J.W., Yfantis,H.G., Stephens,R.M., Caporaso,N.E., Loffredo,C.A. and Ambs,S. Tumor immunobiological differences in prostate cancer between African-American and European-American men, Cancer Res., 68: 927-936, 2008. 4. Martin,D.N., Boersma,B.J., Yi,M., Reimers,M., Howe,T.M., Yfantis,H.G., Tsai,Y.C., Williams,E.H., Lee,D.H., Stephens,R.M., Weissman,A.M. and Ambs,S. Differences in the Tumor Microenvironment between African-American and European-American Breast Cancer Patients, PLoS.ONE., 4: e4531, 2009. 5. Khodarev,N.N., Beckett,M., Labay,E., Darga,T., Roizman,B. and Weichselbaum,R.R. STAT1 is overexpressed in tumors selected for radioresistance and confers protection from radiation in transduced sensitive cells, Proc Natl Acad Sci U.S.A, 101: 1714-1719, 2004. 6. Weichselbaum, R.R., Ishwaran, H., Yoon,T., Nuyten, D.S., Baker, S.W., Khodarev, N., Su, A.W., Shaikh,A.Y., Roach,P., Kreike,B., Roizman,B., Bergh,J., Pawitan,Y., Van de Vijver,M.J. and Minn, A.J. An interferon-related gene signature for DNA damage resistance is a predictive marker for chemotherapy and radiation for breast cancer, Proc. Natl. Acad. Sci.U.S.A, 105: 18490-18495, 2008. 7. Buess, M., Nuyten, D.S., Hastie,T., Nielsen,T., Pesich, R. and Brown, P.O. Characterization of heterotypic interaction effects in vitro to deconvolute global gene expression profiles in cancer, Genome Biol, 8: R191, 2007. Citation Information: Cancer Prev Res 2010;3(12 Suppl):CN10-04.