Genetic regulation of antibody responses to human epidermal growth factor receptor 2 in breast cancer.
Host genetic factors responsible for the interindividual differences in naturally occurring antibody responses to the human epidermal growth factor receptor 2 (HER-2) in human beings have not been identified. The aim of the present investigation was to determine whether immunoglobulin gamma heavy-chain marker (GM) and kappa light-chain marker (KM) allotypes, which are genetic markers of IgG heavy chains and κ-type light chains, respectively, contribute to these differences. A total of 152 Estonian women with breast cancer were characterized for IgG antibodies to HER-2 and allotyped for several GM and KM markers. IgG3 determinant GM 13 was significantly associated with higher HER-2 IgG levels (median IgG titer 800 vs 400, p = 0.007). Other GM allotypes, known to be in linkage disequilibrium with GM 13, were also associated with higher anti-HER-2 antibody levels, albeit not as strongly. These results show that GM allotypes are associated with humoral immunity to HER-2, a finding with potentially significant implications for immunotherapy of breast cancer.
Pandey
Janardan P
JP
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA. pandeyj@musc.edu
Namboodiri
Aryan M
AM
Kurtenkov
Oleg
O
Nietert
Paul J
PJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics / Q000276:immunology*; D004957:Estonia; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D056724:Immunity, Humoral / Q000235:genetics; D007129:Immunoglobulin Gm Allotypes / Q000097:blood / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology
D007129:Immunoglobulin Gm Allotypes; D007145:Immunoglobulin kappa-Chains; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human