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

Immunoglobulin GM and KM allotypes—hereditary antigenic determinants of γ and κ chains, respectively—and Fcγ receptor IIa (FcγRIIa) and FcγRIIIa genes are associated with the immunobiology of several malignant diseases, but their role in humoral immunity to the tumor-associated antigen mucin 1 (MUC1) 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 MUC1 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, FcγRIIa, and FcγRIIIa 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 FcγRIIIa locus was significantly associated with low antibody responsiveness to MUC1 (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 FcγRIIIa and KM loci in humoral immunity to MUC1 in prostate cancer, might be relevant to MUC1-based immunotherapy of this malignancy.