A Polymorphism in CD1e is associated with enhanced immune responses in African American Prostate Cancer Patients (46.40)

Abstract Prostate cancer is the second leading cause of cancer mortality in men older than 40 years in the United States. African American (AA) men and men with a family history of prostate cancer are at a significantly increased risk for developing prostate cancer. A recent study found highly significant differences in the expression of immune regulatory genes and cytokines between tumors from AA and European-American (EA) patients. Therefore, we tested the hypothesis that genetic variations in immune regulatory genes including the CD1 locus may confer an increased disease risk and a poor outcome prostate cancer phenotype in African-American men. Natural Killer T (NKT) cells produce large amounts of cytokines following activation vis-à-vis recognition of lipid antigen presented in the context of CD1d molecules. Prostate tumors commonly express CD1 family members, thus polymorphisms in CD1 genes may be responsible for differences in tumor biology between AA and EA patients. We report that a polymorphism in CD1e occurs commonly in AA but not EA men. When the distribution of this polymorphism was examined in a large cohort (n=562), we found that it is ethnicity specific and occurs primarily in men of African ancestry (P<0.0001). We also observed that this polymorphism strongly influences IFN-γ production following stimulation. Thus, our data indicate that an ethnicity-related polymorphism affects a key function of NKT cells which in turn may modulate prostate cancer biology.