IgG and FcγR genotypes and humoral immunity to mucin 1 in prostate cancer

Immunoglobulin GM and KM allotypes-hereditary antigenic determinants of gamma and kappa chains, respectively and Fey receptor Ha (Fc gamma RlIa) and Fc gamma RIIIa genes are associated with the immunobiology of several malignant diseases, but their role in humoral immunity to the tumor-associated antigen mucin 1 (MUD) in prostate cancer has not been examined. This investigation aimed to determine whether these genes individually or in particular epistatic combinations contribute to the inter-individual variability in the magnitude of antibody responsiveness to MUD in patients with prostate cancer. We genotyped DNA from 127 Caucasian American (CA) and 76 African American (AA) patients with histologically verified adenocarcinoma of the prostate for several GM, KM, Fc gamma RIIa, and Fc gamma RIIIa alleles by molecular methods. We also quantitated antibodies to MUC1 in the plasma from these patients by ELISA. In CA patients, homozygosity for the valine allele at the Fc gamma RIIIa locus was significantly associated with low antibody responsiveness to MUD (p = 0.029). In AA patients, the KM 1/3 heterozygotes had significantly higher anti-MUC1 antibody levels than 1/1 and 3/3 homozygotes (p = 0.044). These results, the first to implicate Fc gamma RIIIa and KM loci in humoral immunity to MUC1 in prostate cancer, might be relevant to MUC1-based immunotherapy of this malignancy. (C) 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.