Endogenous antibody responses to mucin 1 in a large multiethnic cohort of patients with breast cancer and healthy controls: Role of immunoglobulin and Fcγ receptor genes

Abstract

High levels of naturally occurring IgG antibodies to mucin 1 (MUC1), a membrane-bound glycoprotein that is overexpressed in patients with breast cancer, are associated with good prognosis. This suggests that endogenous anti-MUC1 antibodies have a protective effect and, through antibody-mediated host immunosurveillance mechanisms, might contribute to a cancer-free state. To test this possibility, we characterized a large number of multiethnic patients with breast cancer and matched controls for IgG antibodies to MUC1. We also aimed to determine whether the magnitude of anti-MUC1 antibody responsiveness was associated with particular immunoglobulin GM (γ marker), KM (κ marker), and Fcγ receptors (FcγR) genotypes. After adjusting for the confounding variables in a multivariate analysis, we found no significant difference in the levels of anti-MUC1 IgG antibodies between patients and cancer-free controls. However, in patients and controls, particular GM, KM, and FcγR genotypes—individually or epistatically—were significantly associated with the levels of anti-MUC1 IgG antibodies in a racially restricted manner. These findings, if confirmed in an independent investigation, could help identify individuals most likely to benefit from a MUC1-based therapeutic or prophylactic vaccine for MUC1-overexpressing malignancies.

Randomized, Double-Blind, Placebo-Controlled Trial of MUC1 Peptide Vaccine for Prevention of Recurrent Colorectal Adenoma

“…MUC1 mucin is a high molecular weight transmembrane glycoprotein expressed in normal epithelial cells, polarized to the apical surface, and extensively glycosylated (8). Cancer patients with MUC1 positive tumors produce MUC1-specific antibodies and T cells at low levels (9, 10). MUC1-based vaccines raise the immune response to therapeutic levels (11, 12).…”