Skip to main content

Advertisement

SpringerLink
Log in

A genetic variant of FcγRIIIa is strongly associatedwith humoral immunity to cyclin B1 in African American patients with prostate cancer

  • Original Paper
  • Published:
Immunogenetics Aims and scope Submit manuscript

Abstract

There are significant inter-individual differences in naturally occurring antibody responses to the tumor-associated antigen cyclin B1 in healthy subjects with no history of cancer as well as in patients with multiple types of cancer, 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 endogenous antibody levels to cyclin B1 in patients with prostate cancer was associated with immunoglobulin GM and KM alleles, expressed on the constant regions of γ and κ chains, respectively. We also aimed to determine whether particular Fcgamma receptor (FcγR) genotypes, which have been implicated in the immunobiology of several cancers, contribute to the magnitude of humoral immunity to cyclin B1. DNA samples from 129 Caucasian American (CA) and 76 African American (AA) patients with prostate cancer were genotyped for several GM, KM, and FcγR alleles. Plasma samples from these subjects were also characterized for IgG antibodies to cyclin B1. No significant associations were found between any genetic markers and the level of anticyclin B1 antibodies in CA patients. In AA patients, however, homozygosity for the valine allele at the FcγRIIIa locus was strongly associated with low antibody responsiveness to cyclin B1 (p = 0.0007). Since immunity to cyclin B1 has been shown to play a protective role, these results may, at least in part, explain the disproportionately higher rate of mortality in AA patients with prostate cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Balbín M, Grubb A, Abrahamson M, Grubb R (1991) Determination of allotypes G1m(f) and G1m(z) at the genomic level by subclass-specific amplification of DNA and use of allele-specific probes. Exp Clin Immunogenet 8:88–95

    PubMed  Google Scholar 

  • Balbín M, Grubb A, de Lange GG, Grubb R (1994) DNA sequences specific for Caucasian G3m(b) and (g) allotypes: allotyping at the genomic level. Immunogenetics 39:187–193

    Article  PubMed  Google Scholar 

  • Bibeau F, Lopez-Crapez E, Di Fiore F, Thezenas S, Ychou M, Blanchard F, Lamy A, Penault-Llorca F, Frébourg T, Michel P, Sabourin JC, Boissière-Michot F (2009) Impact of FcγRIIa-FcγRIIIa polymorphisms and KRAS mutations on the clinical outcome of patients with metastatic colorectal cancer treated with cetuximab plus irinotecan. J Clin Oncol 27:1122–1129

    Article  PubMed  CAS  Google Scholar 

  • Brusco A, de Lange GG, Boccazzi C, Carbonara AO (1995) Molecular characterization of G2m(n+) and G2m(n-) allotypes. Immunogenetics 42:414–417

    Article  PubMed  CAS  Google Scholar 

  • Egloff AM, Weissfeld J, Land SR, Finn OJ (2005) Evaluation of anti-cyclin B1 serum antibody as a diagnostic and prognostic biomarker for lung cancer. Ann N Y Acad Sci 1062:29–40

    Article  PubMed  CAS  Google Scholar 

  • Jiang XM, Arepally G, Poncz M, McKenzie SE (1996) Rapid detection of the Fc gamma RIIA-H/R 131 ligand-binding polymorphism using an allele-specific restriction enzyme digestion (ASRED). J Immunol Methods 199:55–59

    Article  PubMed  CAS  Google Scholar 

  • Kallakury BV, Sheehan CE, Rhee SJ, Fisher HA, Kaufman RP Jr, Rifkin MD, Ross JS (1999) The prognostic significance of proliferation-associated nucleolar protein p120 expression in prostate adenocarcinoma: a comparison with cyclins A and B1, Ki-67, proliferating cell nuclear antigen, and p34cdc2. Cancer 85:1569–1576

    Google Scholar 

  • Koziol JA, Zhang JY, Casiano CA, Peng XX, Shi FD, Feng AC, Chan EK, Tan EM (2003) Recursive partitioning as an approach to selection of immune markers for tumor diagnosis. Clin Cancer Res 9:5120–5126

    PubMed  CAS  Google Scholar 

  • Lefranc MP, Lefranc G (2012) Human Gm, Km, and Am allotypes and their molecular characterization: a remarkable demonstration of polymorphism. Meth Mol Biol 882:635–680

    Article  CAS  Google Scholar 

  • Lehrnbecher T, Foster CB, Zhu S, Leitman SF, Goldin LR, Huppi K, Chanock SJ (1999) Variant genotypes of the low-affinity Fcgamma receptors in two control populations and a review of low-affinity Fcgamma receptor polymorphisms in control and disease populations. Blood 94:4220–4232

    PubMed  CAS  Google Scholar 

  • Mashal RD, Lester S, Corless C, Richie JP, Chandra R, Propert KJ, Dutta A (1996) Expression of cell cycle-regulated proteins in prostate cancer. Cancer Res 56:4159–4163

    PubMed  CAS  Google Scholar 

  • Moxley G, Gibbs RS (1992) Polymerase chain reaction-based genotyping for allotypic markers of immunoglobulin kappa shows allelic association of Km with kappa variable segment. Genomics 13:104–108

    Article  PubMed  CAS  Google Scholar 

  • Musolino A, Naldi N, Bortesi B, Pezzuolo D, Capelletti M, Missale G, Laccabue D, Zerbini A, Camisa R, Bisagni G, Neri TM, Ardizzoni A (2008) Immunoglobulin G fragment C receptor polymorphisms and clinical efficacy of trastuzumab-based therapy in patients with HER-2/neu-positive metastatic breast cancer. J Clin Oncol 26:1789–1796

    Article  PubMed  CAS  Google Scholar 

  • Namboodiri AM, Pandey JP (2011) Differential inhibition of trastuzumab and cetuximab induced cytotoxicity of cancer cells by IgG1 expressing different GM allotypes. Clin Exp Immunol 166:361–365

    Article  PubMed  CAS  Google Scholar 

  • Pandey JP, Shannon BT, Tsang KY, Fudenberg HH, Camblin JG (1982) Heterozygosity at Gm loci associated with humoral immunity to osteosarcoma. J Exp Med 155:1228–1232

    Article  PubMed  CAS  Google Scholar 

  • Pandey JP, Nietert PJ, Mensdorff-Pouilly S, Klaamas K, Kurtenkov O (2008) Immunoglobulin allotypes influence antibody responses to mucin 1 in patients with gastric cancer. Cancer Res 68:4442–4446

    Article  PubMed  CAS  Google Scholar 

  • Pandey JP, Nietert PJ, Klaamas K, Kurtenkov O (2009) A genetic variant of immunoglobulin γ2 is strongly associated with natural immunity to mucin 1 in patients with breast cancer. Canc Immunol Immunother 58:2025–2029

    Article  CAS  Google Scholar 

  • Pandey JP, Namboodiri AM, Kurtenkov O, Nietert PJ (2010) Genetic regulation of antibody responses to human epidermal growth factor receptor 2 (HER-2) in breast cancer. Hum Immunol 71:1124–1127

    Article  PubMed  CAS  Google Scholar 

  • Schmidt M, Hellwig B, Hammad S, Othman A, Lohr M, Chen Z, Boehm D, Gebhard S, Petry I, Lebrecht A, Cadenas C, Marchan R, Stewart JD, Solbach C, Holmberg L, Edlund K, Kultima HG, Rody A, Berglund A, Lambe M, Isaksson A, Botling J, Karn T, Müller V, Gerhold-Ay A, Cotarelo C, Sebastian M, Kronenwett R, Bojar H, Lehr HA, Sahin U, Koelbl H, Gehrmann M, Micke P, Rahnenführer J, Hengstler JG (2012) A comprehensive analysis of human gene expression profiles identifies stromal immunoglobulin κ C as a compatible prognostic marker in human solid tumors. Clin Cancer Res 18:2695–2703

    Article  PubMed  CAS  Google Scholar 

  • Stockmeyer B, Valerius T, Repp IR, Heijnen IA, Bühring HJ, Deo YM, Kalden JR, Gramatzki M, van de Winkel JG (1997) Preclinical studies with FcγR bispecific antibodies and granulocyte colony-stimulating factor-primed neutrophils as effector cells against HER-2/neu over expressing breast cancer. Cancer Res 57:696–670

    PubMed  CAS  Google Scholar 

  • Taylor RJ, Chan SL, Wood A, Voskens CJ, Wolf JS, Lin W, Chapoval A, Schulze DH, Tian G, Strome SE (2009) FcγRIIIa polymorphisms and cetuximab induced cytotoxicity in squamous cell carcinoma of the head and neck. Canc Immunol Immunother 58:997–1006

    Article  CAS  Google Scholar 

  • Vella LA, Yu M, Fuhrmann SR, El-Amine M, Epperson DE, Finn OJ (2009a) Healthy individuals have T-cell and antibody responses to the tumor antigen cyclin B1 that when elicited in mice protect from cancer. Proc Natl Acad Sci U S A 106:14010–14015

    Article  PubMed  CAS  Google Scholar 

  • Vella LA, Yu M, Phillips AB, Finn OJ (2009b) Immunity against cyclin B1 tumor antigen delays development of spontaneous cyclin B1-positive tumors in p53 (−/−) mice. Ann N Y Acad Sci 1174:68–73

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported in part by a grant from the US Department of Defense (W81XWH-10-1-0479) and by the Biorepository & Research Pathology Services Shared Resource, Hollings Cancer Center, Medical University of South Carolina. We are grateful to the patients and their physicians for their participation and blood donation. We thank Shizhong Bu and Laurel Black for assistance in genotyping and ELISA assays.

Author information

Authors and Affiliations

  1. Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, 29425-2230, USA

    Janardan P. Pandey & Aryan M. Namboodiri

  2. Department of Medicine, Medical University of South Carolina, Charleston, SC, USA

    Emily Kistner-Griffin

Authors
  1. Janardan P. Pandey
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aryan M. Namboodiri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Emily Kistner-Griffin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Janardan P. Pandey.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pandey, J.P., Namboodiri, A.M. & Kistner-Griffin, E. A genetic variant of FcγRIIIa is strongly associatedwith humoral immunity to cyclin B1 in African American patients with prostate cancer. Immunogenetics 65, 91–96 (2013). https://doi.org/10.1007/s00251-012-0660-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00251-012-0660-y

Keywords

Search

Navigation