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

Immunobiology. 2018 Feb;223(2):178-182. doi: 10.1016/j.imbio.2017.10.028. Epub 2017 Oct 18.

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.

Keywords: FcγR genes; GM/KM allotypes; Humoral immunity; MUC1.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibody Formation
  • Brazil / epidemiology
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / immunology*
  • Cohort Studies
  • Continental Population Groups*
  • Ethnic Groups*
  • Female
  • Genotype*
  • Humans
  • Immunoglobulins / blood
  • Immunoglobulins / genetics*
  • Immunologic Surveillance
  • Japan / epidemiology
  • Mucin-1 / immunology*
  • Multivariate Analysis
  • Receptors, IgG / genetics*

Substances

  • Immunoglobulins
  • Mucin-1
  • Receptors, IgG