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Pandey J.P.,Medical University of South Carolina | Kistner-Griffin E.,Medical University of South Carolina | Namboodiri A.M.,Medical University of South Carolina | Iwasaki M.,Nagano Matsushiro General Hospital | And 3 more authors.
Clinical and Experimental Immunology | Year: 2014

Cyclin B1 is a checkpoint protein that regulates cell division from G2 to the M phase. Studies in mice have shown that cyclin B1 vaccine-induced immunity significantly delayed or prevented the spontaneous cancer development later in life.We hypothesized that if these results showing a protective effect of anti-cyclin B1 antibodies could be extrapolated to the human condition, cancer-free individuals should have higher levels of endogenous antibodies than patients with cancers characterized by the over-expression of this tumour-associated antigen. To test this hypothesis, we characterized a large (1739 subjects) number of multi-ethnic patients with breast cancer (which over-expresses cyclin B1) and matched controls for anti-cyclin B1 immunoglobulin (Ig)G antibodies. Multivariate analyses, after adjusting for the covariates, showed that cancer-free individuals had significantly higher levels of naturally occurring IgG antibodies to cyclin B1 than patients with breast cancer (mean ± standard deviation: 148.0 ± 73.6 versus 126.1 ± 67.8 arbitrary units per ml; P < 0.0001). These findings may have important implications for cyclin B1-based immunotherapy against breast cancer and many other cyclin B1-over-expressing malignancies. © 2014 British Society for Immunology. Source


Pandey J.P.,Medical University of South Carolina | Gao G.,Virginia Commonwealth University | Namboodiri A.M.,Medical University of South Carolina | Iwasaki M.,National Cancer Center | And 3 more authors.
Journal of Infectious Diseases | Year: 2016

Increasing evidence implicates human cytomegalovirus (HCMV) in the etiopathogenesis of breast cancer. Antibodies to this virus in patients with breast cancer have been reported, but no large-scale studies have been conducted to determine whether the antibody levels differ between patients and matched controls. Using specimens from a large (1712 subjects) multiethnic case-control study, we aimed to determine whether the levels of antibodies to the HCMV glycoprotein B (gB) differed between patients and controls and whether they were associated with particular immunoglobulin γ marker (GM), κ marker (KM), and Fcγ receptor (FcγR) genotypes. A combined analysis showed that anti-gB immunoglobulin G antibody levels were higher in healthy controls than in patients (P <. 0001). Stratified analyses showed population-specific differences in the magnitude of anti-gB antibody responsiveness and in the contribution of particular GM, KM, and FcγR genotypes to these responses. These findings may have implications for HCMV-based immunotherapy against breast cancer and other HCMV-associated diseases. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. Source


Iwasaki M.,Research Center for Cancer Prevention and Screening | Kasuga Y.,Nagano Matsushiro General Hospital | Yokoyama S.,Red Cross | Onuma H.,Red Cross | And 9 more authors.
BMC Medicine | Year: 2011

Background: Differences in sex hormone levels among populations might contribute to the variation in breast cancer incidence across countries. Previous studies have shown higher breast cancer incidence and mortality among Japanese Brazilians than among Japanese. To clarify the difference in hormone levels among populations, we compared postmenopausal endogenous sex hormone levels among Japanese living in Japan, Japanese Brazilians living in the state of São Paulo, and non-Japanese Brazilians living in the state of São Paulo.Methods: A cross-sectional study was conducted using a control group of case-control studies in Nagano, Japan, and São Paulo, Brazil. Participants were postmenopausal women older than 55 years of age who provided blood samples. We measured estradiol, estrone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), testosterone and free testosterone by radioimmunoassay; bioavailable estradiol by the ammonium sulfate precipitation method; and sex hormone-binding globulin (SHBG) by immunoradiometric assay. A total of 363 women were included for the present analyses, comprising 185 Japanese, 44 Japanese Brazilians and 134 non-Japanese Brazilians.Results: Japanese Brazilians had significantly higher levels of estradiol, bioavailable estradiol, estrone, testosterone and free testosterone levels, and lower SHBG levels, than Japanese. Japanese Brazilians also had significantly higher levels of bioavailable estradiol, estrone and DHEAS and lower levels of SHBG and androstenedione than non-Japanese Brazilians. Levels of estradiol, testosterone and free testosterone, however, did not differ between Japanese Brazilians and non-Japanese Brazilians. These differences were observed even after adjustment for known breast cancer risk factors. We also found an increase in estrogen and androgen levels with increasing body mass index, but no association for most of the other known risk factors.Conclusions: We found higher levels of estrogens and androgens in Japanese Brazilians than in Japanese and levels similar to or higher than in non-Japanese Brazilians. Our findings may help explain the increase in the incidence and mortality rate of breast cancer among Japanese Brazilians. © 2011 Iwasaki et al; licensee BioMed Central Ltd. Source


Iwasaki M.,Research Center for Cancer Prevention and Screening | Shimada N.,University of Tokyo | Kasuga Y.,Nagano Matsushiro General Hospital | Yokoyama S.,Red Cross | And 10 more authors.
Breast Cancer Research and Treatment | Year: 2011

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. © 2011 Springer Science+Business Media, LLC. Source


Pandey J.P.,Medical University of South Carolina | Namboodiri A.M.,Medical University of South Carolina | Kistner-Griffin E.,Medical University of South Carolina | Iwasaki M.,Research Center for Cancer Prevention and Screening | And 3 more authors.
Clinical and Experimental Immunology | Year: 2013

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. © 2012 British Society for Immunology. Source

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