Document Detail

Racially restricted contribution of immunoglobulin Fcγ and Fcγ receptor genotypes to humoral immunity to human epidermal growth factor receptor 2 in breast cancer.
MedLine Citation:
PMID:  23379433     Owner:  NLM     Status:  MEDLINE    
Tumour-associated antigen human epidermal growth factor receptor 2 (HER2) is over-expressed in 25-30% of breast cancer patients and is associated with poor prognosis. Naturally occurring anti-HER2 antibody responses have been described in patients with HER2 over-expressing tumours. There is significant interindividual variability in antibody responsiveness, but the host genetic factors responsible for this variability are poorly understood. The aim of the present investigation was to determine whether immunoglobulin genetic markers [GM (genetic determinants of γ chains)] and Fcγ receptor (FcγR) alleles contribute to the magnitude of natural antibody responsiveness to HER2 in patients with breast cancer. A total of 855 breast cancer patients from Japan and Brazil were genotyped for several GM and FcγR alleles. They were also characterized for immunoglobulin (Ig)G antibodies to HER2. In white subjects (n = 263), GM 23-carriers had higher levels of anti-HER2 antibodies than non-carriers of this allele (p = 0·004). At the GM 5/21 locus, the homozygotes for the GM 5 allele had higher levels of anti-HER2 antibodies than the other two genotypes (P = 0·0067). In black subjects (n = 42), FcγRIIa-histidine/histidine homozygotes and FcγRIIIa-phenylalanine/valine heterozygotes were associated with high antibody responses (P = 0·0071 and 0·0275, respectively). FcγR genotypes in white subjects and GM genotypes in black subjects were not associated with anti-HER2 antibody responses. No significant associations were found in other study groups. These racially restricted contributions of GM and FcγR genotypes to humoral immunity to HER2 have potential implications for immunotherapy of breast cancer.
J P Pandey; A M Namboodiri; E Kistner-Griffin; M Iwasaki; Y Kasuga; G S Hamada; S Tsugane
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Clinical and experimental immunology     Volume:  171     ISSN:  1365-2249     ISO Abbreviation:  Clin. Exp. Immunol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-05     Completed Date:  2013-04-02     Revised Date:  2014-03-06    
Medline Journal Info:
Nlm Unique ID:  0057202     Medline TA:  Clin Exp Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  273-7     Citation Subset:  IM    
Copyright Information:
© 2012 British Society for Immunology.
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MeSH Terms
African Continental Ancestry Group / genetics
Asian Continental Ancestry Group / genetics
Breast Neoplasms / genetics*,  immunology*,  therapy
Continental Population Groups / genetics*
European Continental Ancestry Group / genetics
Immunity, Humoral / genetics*
Immunoglobulin Gm Allotypes / genetics*
Receptor, erbB-2 / immunology*
Receptors, IgG / genetics*
Reg. No./Substance:
0/Immunoglobulin Gm Allotypes; 0/Receptors, IgG; EC protein, human; EC, erbB-2

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