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Breast Cancer Research and Treatment

, Volume 126, Issue 2, pp 497–505 | Cite as

Fragment c gamma receptor gene polymorphisms and breast cancer risk in case–control studies in Japanese, Japanese Brazilians, and non-Japanese Brazilians

  • Motoki Iwasaki
  • Naoki Shimada
  • Yoshio Kasuga
  • Shiro Yokoyama
  • Hiroshi Onuma
  • Hideki Nishimura
  • Ritsu Kusama
  • Gerson S. Hamada
  • Ines N. Nishimoto
  • Hirofumi Iyeyasu
  • Juvenal MotolaJr.
  • Fábio M. Laginha
  • Roberto Anzai
  • Shoichiro Tsugane
Epidemiology

Abstract

Previous studies showing the presence of antibodies against tumor-associated antigens in healthy individuals suggest that antibody-dependent cell cytotoxicity (ADCC) might play a role in the development of breast cancer. We hypothesized that functional polymorphisms in fragment c gamma receptor (FcgR) genes were associated with breast cancer risk. We conducted hospital-based case–control studies of patients aged 20–74 years with invasive breast cancer, and matched controls from medical checkup examinees in Nagano, Japan and from cancer-free patients in São Paulo, Brazil. A total of 869 pairs (403 Japanese, 80 Japanese Brazilians and 386 non-Japanese Brazilians) were genotyped for two single nucleotide polymorphisms (SNPs): a histidine (H)/arginine (R) polymorphism at position 131 of FcgRIIa (FcgRIIa H131R) and a valine (V)/phenylalanine (F) polymorphism at position 158 of FcgRIIIa (FcgRIIIa F158V). We found no statistically significant association between either of the two SNPs and breast cancer risk regardless of population. In analyses of the three populations combined, adjusted odds ratio (OR) was 0.93 [95% confidence interval (CI) 0.66–1.32] for women with the R/R versus H/H genotype of the FcgRIIa H131R polymorphism and 1.04 (95% CI 0.69–1.57) for the V/V versus F/F genotype of the FcgRIIIa F158V polymorphism. On combination of the two SNPs, compared to women with both the R/R genotype of the FcgRIIa H131R polymorphism and F/F genotype of the FcgRIIIa F158V polymorphism, the adjusted OR for women with both the H/H and V/V genotype was 0.68 (95% CI 0.37–1.27). In conclusion, our findings suggest that ADCC might not play a major role in the etiology of breast cancer.

Keywords

Fragment c gamma receptor gene Single nucleotide polymorphism Breast cancer Case–control study Immigrants 

Abbreviations

ADCC

Antibody-dependent cell cytotoxicity

CI

Confidence interval

FcgR

Fragment c gamma receptor

HER2

Human epidermal growth factor receptor 2

MUC1

Epithelial mucin

NK

Natural killer

OR

Odds ratio

SNP

Single nucleotide polymorphism

Notes

Acknowledgments

This study was supported by a Grant-in-Aid for Research on Risk of Chemical Substances from the Ministry of Health, Labour and Welfare of Japan, and Grants-in-Aid for Scientific Research on Priority Areas (17015049) and for Young Scientists (B) (22700934) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and the Japan Society for the Promotion of Science, and Foundation for Promotion of Cancer Research in Japan. We are grateful to the participants of the “São Paulo-Japan Breast Cancer Study Group”: T. Hanaoka, M. Kobayashi, J. Ishihara, S. Ikeda, and C. Nishimoto (Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo); C. I. Yamaguchi, C. M. Kunieda, and S. S. Sugama (Nikkei Disease Prevention Center, São Paulo); C. K. Taniguchi and J. A. Marques (Departamento de Ginecologia, Hospital Pérola Byington, São Paulo); M. R. Eichhorn (Departamento de Nutrição, Hospital Pérola Byington, São Paulo); M. M. Netto, M. S. Maciel, S. M. T. Carvalho, J. B. D. Collins, and C. E. M. Fontes (Departamento de Mastologia, Hospital A.C. Camargo, São Paulo); L. P. Kowalski and J. M. F. Toyota (Departamento de Cirurgia de Cabeça e Pescoço e Otorrinolaringologia, A. C. Camargo Hospital, São Paulo); E. M. Barbosa (Departamento de Mastologia, Instituto Brasileiro de Controle ao Câncer, São Paulo); O. Ferraro (Departamento de Mastologia, Hospital do Servidor Público Estadual Francisco Morato de Oliveira, São Paulo); E. H. Hotta and D. A. Petti (Instituto de Ginecologia e Mastologia, Hospital Beneficencia Portuguesa); and S. Mendes (Instituto Brasileiro de Mastologia e Ginecologia, Hospital Beneficencia Portuguesa).

Conflict of interest

All authors declare that we have no conflict of interest in connection with this paper.

References

  1. 1.
    Ferlay J, Bray F, Pisani P et al (2004) GLOBOCAN 2002 cancer incidence, mortality and prevalence worldwide. IARC CancerBase No. 5, version 2.0. IARC Press, LyonGoogle Scholar
  2. 2.
    Matsuda T, Marugame T, Kamo K et al (2009) Cancer incidence and incidence rates in Japan in 2003: based on data from 13 population-based cancer registries in the Monitoring of Cancer Incidence in Japan (MCIJ) Project. Jpn J Clin Oncol 39:850–858PubMedCrossRefGoogle Scholar
  3. 3.
    Key T, Appleby P, Barnes I et al (2002) Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst 94:606–616PubMedGoogle Scholar
  4. 4.
    Finn OJ (2008) Cancer immunology. N Engl J Med 358:2704–2715PubMedCrossRefGoogle Scholar
  5. 5.
    Imai K, Matsuyama S, Miyake S et al (2000) Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population. Lancet 356:1795–1799PubMedCrossRefGoogle Scholar
  6. 6.
    Dewan MZ, Takada M, Terunuma H et al (2009) Natural killer activity of peripheral-blood mononuclear cells in breast cancer patients. Biomed Pharmacother 63:703–706PubMedCrossRefGoogle Scholar
  7. 7.
    Reuschenbach M, von Knebel Doeberitz M, Wentzensen N (2009) A systematic review of humoral immune responses against tumor antigens. Cancer Immunol Immunother 58:1535–1544PubMedCrossRefGoogle Scholar
  8. 8.
    Croce MV, Isla Larrain MT, Price MR et al (2001) Detection of circulating mammary mucin (Muc1) and MUC1 immune complexes (Muc1-CIC) in healthy women. Int J Biol Markers 16:112–120PubMedGoogle Scholar
  9. 9.
    Croce MV, Isla Larrain MT, Capafons A et al (2001) Humoral immune response induced by the protein core of MUC1 mucin in pregnant and healthy women. Breast Cancer Res Treat 69:1–11PubMedCrossRefGoogle Scholar
  10. 10.
    Forsman LM, Jouppila PI, Andersson LC (1984) Sera from multiparous women contain antibodies mediating cytotoxicity against breast carcinoma cells. Scand J Immunol 19:135–139PubMedCrossRefGoogle Scholar
  11. 11.
    Koene HR, Kleijer M, Algra J et al (1997) Fc gammaRIIIa-158V/F polymorphism influences the binding of IgG by natural killer cell Fc gammaRIIIa, independently of the Fc gammaRIIIa-48L/R/H phenotype. Blood 90:1109–1114PubMedGoogle Scholar
  12. 12.
    Dall’Ozzo S, Tartas S, Paintaud G et al (2004) Rituximab-dependent cytotoxicity by natural killer cells: influence of FCGR3A polymorphism on the concentration–effect relationship. Cancer Res 64:4664–4669PubMedCrossRefGoogle Scholar
  13. 13.
    Salmon JE, Edberg JC, Brogle NL et al (1992) Allelic polymorphisms of human Fc gamma receptor IIA and Fc gamma receptor IIIB. Independent mechanisms for differences in human phagocyte function. J Clin Invest 89:1274–1281PubMedCrossRefGoogle Scholar
  14. 14.
    Warmerdam PA, van de Winkel JG, Vlug A et al (1991) A single amino acid in the second Ig-like domain of the human Fc gamma receptor II is critical for human IgG2 binding. J Immunol 147:1338–1343PubMedGoogle Scholar
  15. 15.
    Spector NL, Blackwell KL (2009) Understanding the mechanisms behind trastuzumab therapy for human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol 27:5838–5847PubMedCrossRefGoogle Scholar
  16. 16.
    Musolino A, Naldi N, Bortesi B et al (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 26:1789–1796PubMedCrossRefGoogle Scholar
  17. 17.
    van Sorge NM, van der Pol WL, van de Winkel JG (2003) FcgammaR polymorphisms: implications for function, disease susceptibility and immunotherapy. Tissue Antigens 61:189–202PubMedCrossRefGoogle Scholar
  18. 18.
    Iwasaki M, Hamada GS, Nishimoto IN et al (2009) Dietary isoflavone intake and breast cancer risk in case–control studies in Japanese, Japanese Brazilians, and non-Japanese Brazilians. Breast Cancer Res Treat 116:401–411PubMedCrossRefGoogle Scholar
  19. 19.
    Shimada N, Iwasaki M, Kasuga Y et al (2009) Genetic polymorphisms in estrogen metabolism and breast cancer risk in case–control studies in Japanese, Japanese Brazilians and non-Japanese Brazilians. J Hum Genet 54:209–215PubMedCrossRefGoogle Scholar
  20. 20.
    Wang SS, Cerhan JR, Hartge P et al (2006) Common genetic variants in proinflammatory and other immunoregulatory genes and risk for non-Hodgkin lymphoma. Cancer Res 66:9771–9780PubMedCrossRefGoogle Scholar
  21. 21.
    Kyogoku C, Dijstelbloem HM, Tsuchiya N et al (2002) Fcgamma receptor gene polymorphisms in Japanese patients with systemic lupus erythematosus: contribution of FCGR2B to genetic susceptibility. Arthritis Rheum 46:1242–1254PubMedCrossRefGoogle Scholar
  22. 22.
    Metes D, Ernst LK, Chambers WH et al (1998) Expression of functional CD32 molecules on human NK cells is determined by an allelic polymorphism of the FcgammaRIIC gene. Blood 91:2369–2380PubMedGoogle Scholar
  23. 23.
    Suzuki R, Orsini N, Saji S et al (2009) Body weight and incidence of breast cancer defined by estrogen and progesterone receptor status—a meta-analysis. Int J Cancer 124:698–712PubMedCrossRefGoogle Scholar
  24. 24.
    World Cancer Research Fund and American Institute for Cancer Research (2007) Food, nutrition, physical activity and the prevention of cancer: a global perspective. American Institute, Washington, DCGoogle Scholar
  25. 25.
    Curado MP, Edwards B, Shin HR et al (2007) cancer incidence in five continents, vol IX. IARC Scientific Publications No. 160. IARC, LyonGoogle Scholar
  26. 26.
    Althuis MD, Fergenbaum JH, Garcia Closas M et al (2004) Etiology of hormone receptor-defined breast cancer: a systematic review of the literature. Cancer Epidemiol Biomark Prev 13:1558–1568Google Scholar
  27. 27.
    Sorlie T, Perou CM, Tibshirani R et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98:10869–10874PubMedCrossRefGoogle Scholar
  28. 28.
    Carey LA, Perou CM, Livasy CA et al (2006) Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA 295:2492–2502PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Motoki Iwasaki
    • 1
  • Naoki Shimada
    • 2
  • Yoshio Kasuga
    • 3
  • Shiro Yokoyama
    • 4
  • Hiroshi Onuma
    • 4
  • Hideki Nishimura
    • 5
  • Ritsu Kusama
    • 6
  • Gerson S. Hamada
    • 7
  • Ines N. Nishimoto
    • 8
  • Hirofumi Iyeyasu
    • 9
  • Juvenal MotolaJr.
    • 10
  • Fábio M. Laginha
    • 10
  • Roberto Anzai
    • 11
  • Shoichiro Tsugane
    • 1
  1. 1.Epidemiology and Prevention Division, Research Center for Cancer Prevention and ScreeningNational Cancer CenterTokyoJapan
  2. 2.The Clinical Training CenterThe University of Tokyo HospitalTokyoJapan
  3. 3.Department of SurgeryNagano Matsushiro General HospitalNaganoJapan
  4. 4.Department of Breast and Thyroid SurgeryNagano Red Cross HospitalNaganoJapan
  5. 5.Department of SurgeryNagano Municipal HospitalNaganoJapan
  6. 6.Department of SurgeryNagano Hokushin General HospitalNaganoJapan
  7. 7.Nikkei Disease Prevention CenterSão PauloBrazil
  8. 8.Statistical Section, Head and Neck Surgery and Otorhinolaryngology DepartmentHospital A.C. CamargoSão PauloBrazil
  9. 9.Breast Surgery DepartmentHospital A.C. CamargoSão PauloBrazil
  10. 10.Department of Breast SurgeryHospital Pérola ByingtonSão PauloBrazil
  11. 11.Department of Breast SurgeryHospital Santa CruzSão PauloBrazil

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