Abstract B51: An interferon λ 4 genotype is linked to a gene expression signature in prostate tumors of African American men

Abstract

Abstract 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-American (AA) men still have the highest prostate cancer mortality among all U.S. racial and ethnic groups. In a recent study, we examined the tumor biology of prostate cancer comparing AA patients with European-American (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. Intriguingly, an interferon gene signature was detected in AA prostate that may relate to an unknown etiologic agent in disease pathology. This signature occurred commonly in AA men in two independent patient cohorts and may influence therapeutic outcome because it is analogous to a recently discovered interferon-related DNA damage resistance signature (termed IRDS), which predicts resistance to chemotherapy and radiation in breast cancer and perhaps other epithelial cancers. Here, we assessed whether the development of this signature could be functionally linked to a germline variant allele (rs368234815-ΔG) that is frequently found in subjects of African ancestry (~65% allele frequency) but is less common in subjects of European ancestry (~30% allele frequency). Carriers of ΔG can express a recently discovered interferon, termed interferon lambda 4 (IFNL4), while the rs368234815-TT allele eliminates expression. We genotyped DNA from tumors that have previously been characterized for presence of the interferon signature and found that the ability to generate IFNL4 (in carriers of the ΔG allele) was significantly associated with the presence of this signature (P < 0.001, n = 44), indicating that IFNL4 expression may be involved. In summary, our study links a germline genetic variant in IFNL4 to the occurrence of a clinically relevant interferon signature in prostate tumors of African-American men. Future research will assess how this genetic variant may influence disease outcome. Citation Format: Symone Jordan, Wei Tang, Tiffany Wallace, Tiffany Dorsey, Ming Yi, Robert Stephens, Ludmila Prokunina-Olsson, Stefan Ambs. An interferon λ 4 genotype is linked to a gene expression signature in prostate tumors of African American men. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B51.