Fragment c gamma receptor gene polymorphisms and breast cancer risk in case–control studies in Japanese, Japanese Brazilians, and non-Japanese Brazilians
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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.
KeywordsFragment c gamma receptor gene Single nucleotide polymorphism Breast cancer Case–control study Immigrants
Antibody-dependent cell cytotoxicity
Fragment c gamma receptor
Human epidermal growth factor receptor 2
Single nucleotide polymorphism
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.
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