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Immunoglobulin Allotypes Influence Antibody Responses to Mucin 1 in Patients with Gastric Cancer

Departments of ¹ Microbiology and Immunology, and ² Biostatistics, Bioinformatics and Epidemiology, Medical University of South Carolina, Charleston, South Carolina; ³ Department of Obstetrics and Gynecology, Vrije Universiteit Medical Center, Amsterdam, the Netherlands; and ⁴ Department of Oncology and Immunology, National Institute for Health Development, Tallinn, Estonia

Requests for reprints: Janardan P. Pandey, Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425-2230. Phone: 843-792-4360; Fax: 843-792-4882; E-mail: pandeyj{at}musc.edu.

Key Words: Allotypes • Immune response • MUC1

There are significant interindividual differences in naturally occurring antibody responses to the tumor-associated antigen mucin 1 (MUC1), but the host genetic factors that might contribute to these differences have not been identified. The aim of the present investigation was to determine whether the variation in naturally occurring antibody levels to MUC1 in patients with gastric cancer is associated with GM and KM allotypes, genetic markers of IgG heavy chains and -type light chains, respectively. A total of 169 Caucasian subjects with gastric cancer were allotyped for several GM and KM markers. These subjects were also characterized for IgG and IgM antibodies to MUC1. GM 3 23 5,13 phenotype was highly significantly associated with MUC1 IgG levels; subjects with this phenotype had lower antibody levels compared with those lacking this phenotype (median IgG level 65.5 relative units versus 91.0 relative units, P = 0.0058). In addition, this phenotype had an interactive effect with KM phenotypes on the levels of IgG antibodies to this antigen (P = 0.0081). Levels of MUC1 IgM antibodies were not associated with these genetic markers. These results show, for the first time, that GM and KM allotypes contribute to the interindividual differences in humoral immunity to MUC1. [Cancer Res 2008;68(11):4442–6]