Tomoyuki Hanaoka

Showa University, Shinagawa, Tōkyō, Japan

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Publications (72)234.37 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Polycyclic aromatic hydrocarbons (PAHs) are multiple compounds that include many carcinogens. We conducted a cross-sectional study in steel plant workers in Anshan, China, to identify biomarkers that reflect the carcinogenicity of PAHs. Subjects were 57 workers and 20 controls. Level of personal exposure to PAHs was measured using GC-MS. In accordance with the assessment methods defined by the United States Environmental Protection Agency (US EPA), 15 PAHs were selected for the analysis. For the measurement of urinary metabolites, urine samples were treated with β-glucuronidase and analyzed using HPLC with a fluorescence detector. The mean range of personal exposure to 15 PAHs (total PAHs) was 178.85, 47.08-1,329.45 (geometric mean, 5th and 95th percentile) μg/m(3). Ten known urinary metabolites (1-hydroxynaphthalene, 2-hydroxynaphthalene, 2-hydroxyfluorene, 1-hydroxyphenanthrene, 3-hydroxyphenanthrene, 9-hydroxyphenanthrene, 1-hydroxypyrene, 3-hydroxybenz[a]anthracene, 6-hydroxychrysene, and 3-hydroxybenzo[a]pyrene) and four unknown peaks were detected. The highest correlation was between total PAHs and urinary 2-hydroxynaphthalene (Spearman r = 0.716, P < 0.01). Among the detected urinary metabolites, 2-hydroxyfluorene, 1-hydroxyphenanthrene, 3-hydroxyphenanthrene, and 1-hydroxypyrene were found to correlate significantly with the "Σ carcinogenic potency of PAHs" (sum of seven carcinogenic PAHs calculated from the levels of personal PAHs and relative potency factors), and with the greatest correlation found for 1-hydroxypyrene (Spearman r = 0.630, P < 0.01). The analysis of personal exposure to 15 PAHs and 10 urinary metabolites, and calculation of Σ carcinogenic potency, indicated that urinary 1-hydroxypyrene was the most comprehensive carcinogenic biomarker of exposure to PAHs.
    International Archives of Occupational and Environmental Health 10/2013; 87(7). DOI:10.1007/s00420-013-0913-6 · 2.20 Impact Factor
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    ABSTRACT: Subjects with severe motor and intellectual disability (SMID) are considered to be debilitated and at high risk of influenza infection. However, the safety and immunogenicity of pandemic H1N1 (pH1N1) vaccine in these subjects have not been reported. We measured the hemagglutination inhibition antibody titer and calculated the geometric mean titer ratio (GMTR), seroprotection rate, and seroconversion rate in 104 subjects with SMID (mean age±standard deviation 40.1±12.9 years), and in 179 healthcare workers (40.7±10.4 years) in a long-term care facility. Antibody responses after the first dose of pH1N1 vaccine among workers were greater than the European Medicines Evaluation Agency criteria and US Food and Drug Administration (FDA) criteria: the seroprotection rate was 79.9% (95% confidence interval (CI) 73.3-85.5), the seroconversion rate was 77.9% (95%CI: 70.8-84.0), and GMTR was 7.3 (95%CI: 6.9-7.8). Responses among subjects with SMID were lower than the FDA criteria: the seroprotection rate was 56.3% (95%CI: 46.2-66.1), the seroconversion rate was 54.1% (95%CI: 43.7-64.2), and GMTR was 5.4 (95%CI: 4.9-5.9). Any additional antibody response induced by the second dose of vaccine among subjects with SMID was limited. Multivariate analysis indicated that subjects with SMID had a significantly lower seroprotection rate (odds ratio (OR) 0.37, 95%CI: 0.20-0.66) and seroconversion rate (OR 0.34, 95%CI: 0.20-0.59) than healthcare workers. No serious adverse reaction was reported in either group. These results indicate that a single dose of pH1N1 vaccine does not induce sufficient immunity among subjects with SMID, and a second dose is likely to be ineffective because of diminished immunogenicity. Further study is required to determine if vaccination over consecutive influenza seasons can improve immunogenicity in subjects with SMID.
    Vaccine 09/2011; 29(46):8323-9. DOI:10.1016/j.vaccine.2011.08.097 · 3.62 Impact Factor
  • G Pan · T Hanaoka · L Yu · J Na · Y Yamano · K Hara · M Ichiba · T Nakadate · R Kishi · P Wang · H Yin · S Zhang · Y Feng ·
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    ABSTRACT: The knowledge on the dose-response relationships between cumulative phthalate exposure and reproductive hormones in human are lacking. To assess the characteristics of the associations between hazard index (HI) of cumulative di-n-butylphthalate (DBP) and di-2-ethylhexylphthalate (DEHP) exposures and serum concentrations of free testosterone (fT), estradiol, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), we used restricted cubic spline function to characterize the dose-response curves between the HI values and reproductive hormones for 74 male workers occupationally exposed to high levels of DBP and DEHP, and 63 male construction workers as comparison group matched for age and smoking status. The median of HI value was 5.30 for exposed workers, 53.0-fold that of unexposed workers (0.10). 89.2% of exposed workers and 1.6% of unexposed workers have HI over 1.00. We observed a borderline significantly negative association between HI and fT in exposed workers (r=-0.195, p=0.096), but not in unexposed workers. The exposed workers showed inverted long-tailed J-shaped fT and FSH curves, and small changes in the LH curve, whereas unexposed workers had inverted and flattened-S-shaped fT and mirror-S-shaped LH and FSH curves. Both T production and hypothalamo-pituitary-testis (HPT) axis function were damaged in workers with high HI of phthalate exposures. HPT feedback function was activated in workers with both high and low HI, and plays an important role in preventing fT level from further decreasing with a rise in HI.
    International Journal of Andrology 07/2011; 34(5 Pt 2):e397-406. DOI:10.1111/j.1365-2605.2011.01201.x · 3.70 Impact Factor
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    ABSTRACT: We tested the hypothesis that polymorphisms in cytochrome P450c17alpha (CYP17), aromatase (CYP19), 17beta-hydroxysteroid dehydrogenase type I (17beta-HSD1) and sex hormone-binding globulin (SHBG) genes may modify the association between isoflavone intake and breast cancer risk. We conducted hospital-based, case-control studies in Nagano, Japan and Sao Paulo, Brazil. A total of 846 pairs (388 Japanese, 79 Japanese Brazilians, and 379 non-Japanese Brazilians) completed validated food frequency questionnaires. Four single nucleotide polymorphisms (SNPs) in CYP17 (rs743572), CYP19 (rs10046), 17beta-HSD1 (rs605059), and SHBG (rs6259) genes were genotyped. We found no association between the 4 SNPs and breast cancer risk. In combination analyses of isoflavone intake and SNPs, an inverse association between intake and risk was limited to women with at least one A allele of the rs605059 polymorphism for all 3 populations, albeit without statistical significance. For the rs6259 polymorphism, the inverse association was limited to postmenopausal Japanese with the GG genotype (odds ratio [OR] for highest vs. lowest tertile = 0.50, 95% confidence interval [CI] = 0.29-0.87; P for trend < 0.01), and to non-Japanese Brazilians with at least one A allele (OR for consumers vs. nonconsumer = 0.21, 95% CI = 0.06-0.77). We found no remarkable difference for the rs743572 and rs10046 polymorphisms. Our findings suggest that polymorphisms in the 17beta-HSD1 and SHBG genes may modify the association between isoflavone intake and breast cancer risk.
    Nutrition and Cancer 04/2010; 62(4):466-75. DOI:10.1080/01635580903441279 · 2.32 Impact Factor
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    ABSTRACT: Although the prognosis for survival in people with severe functional disabilities is a serious concern for their families and health care practitioners, there have been few reports on survival rates for this population. Every year, the Japanese Association of Welfare for Persons with Severe Motor and Intellectual Disability collects anonymous records of individual registrations and deaths from all private and public institutions, excepting national institutions. We used these data to estimate the prognosis for survival. We reviewed the records of 3221 people with severe motor and intellectual disabilities (SMID); all subjects had lived in one of 119 public or private institutions in Japan between 1961 and 2003. Kaplan-Meier survival estimates were calculated according to disability type and birth year range. Of the 3221 persons, 2645 were alive and 576 had died. The survival rate at the age of 20 for all subjects was 79% (95% confidence interval, 78%-81%). Among people who were unable to sit, those with lower intelligence quotients had lower survival rates. The survival rate among people with SMID housed in public and private institutions in Japan was much worse than that of the general population, and has not improved since the 1960s.
    Journal of Epidemiology 11/2009; 20(1):77-81. DOI:10.2188/jea.JE20090024 · 3.02 Impact Factor
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    ABSTRACT: Phthalates may act as an estrogen and are a potential risk factor for estrogen-related diseases such as endometriosis. We assessed the association between phthalate exposure and endometriosis in 166 consecutive women who presented at a university hospital for consultation regarding infertility. The subjects were interviewed and provided a urine specimen prior to a laparoscopic diagnosis of endometriosis. They were then categorized by the severity of endometriosis as controls (stages 0-I) and cases (stages II-IV). Urinary concentrations of the phthalate metabolites monoethyl phthalate, mono-n-butyl phthalate, monobenzyl phthalate, mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-oxohexyl) phthalate, and mono(2-ethyl-5-hydroxyhexyl) phthalate were measured in 57 cases and 80 controls using high-performance liquid chromatography isotope-dilution tandem mass spectrometry. Adjusted odds ratios for endometriosis in relation to dichotomized individual phthalate metabolites (standardized for creatinine) were calculated. No significant association between endometriosis and any urinary creatinine-adjusted phthalate monoester was seen. Adjusted odds ratio (95% confidence interval) for higher dichotomized MEHP by endometriosis was 1.57 (0.74-3.30). No monotonic trend was seen in urinary creatinine-adjusted concentration of phthalate metabolites by endometriosis stage (p=0.23-0.90). Our results do not support the hypothesis that higher urinary concentrations of phthalate metabolites are associated with the risk of endometriosis in infertile Japanese women.
    Science of The Total Environment 10/2009; 408(1):37-42. DOI:10.1016/j.scitotenv.2009.09.012 · 4.10 Impact Factor
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    ABSTRACT: Although epidemiologic studies have shown an inverse association between isoflavones and breast cancer risk, little evidence for a dose–response relation is available. We conducted hospital-based case–control studies of patients aged 20–74years with primary, incident, histologically confirmed 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 850 pairs (390 Japanese, 81 Japanese Brazilians and 379 non-Japanese Brazilians) completed validated food frequency questionnaires. The odds ratio of breast cancer according to isoflavone intake was estimated using a conditional logistic regression model. We found a statistically significant inverse association between isoflavone intake and the risk of breast cancer for Japanese Brazilians and non-Japanese Brazilians. For Japanese, a non-significant inverse association was limited to postmenopausal women. In the three populations combined, breast cancer risk linearly decreased from ‘no’ to ‘moderate’ isoflavone intake and thereafter leveled off. Compared to non-consumers, adjusted odds ratios (95% confidence interval) for consumers in increasing quintile intake categories (median intake in each category: 8.7, 23.1, 33.8, 45.7, and 71.3mg/day) were 0.69 (0.44–1.09), 0.54 (0.31–0.94), 0.45 (0.26–0.77), 0.34 (0.19–0.62), and 0.43 (0.24–0.76), respectively. Overall, we found an inverse association between dietary isoflavone intake and risk of breast cancer. Our finding suggests a risk-reducing rather than risk-enhancing effect of isoflavones on breast cancer within the range achievable from dietary intake alone. In addition, women may benefit from risk reduction if they consume at least moderate amounts of isoflavones.
    Breast Cancer Research and Treatment 07/2009; 116(2):401-411. DOI:10.1007/s10549-008-0168-1 · 3.94 Impact Factor
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    ABSTRACT: Epidemiologic studies have shown an inverse association between isoflavones and breast cancer risk. Because isoflavones bind estrogen receptors, we hypothesized that polymorphisms in the estrogen receptor genes might modify the association between isoflavone intake and breast cancer risk. We conducted hospital-based case-control studies of patients aged 20-74 years with primary, incident, histologically confirmed invasive breast cancer, and matched controls from among medical checkup examinees in Nagano, Japan, and from cancer-free patients in São Paulo, Brazil. A total of 846 pairs (388 Japanese, 79 Japanese Brazilians and 379 non-Japanese Brazilians) completed validated food frequency questionnaires, and provided blood samples. Five single nucleotide polymorphisms in the estrogen receptor alpha (rs9340799, rs1913474, and rs2234693) and beta (rs4986938 and rs1256049) genes were genotyped. We found no consistent association between the five single nucleotide polymorphisms and breast cancer risk among the three populations. In analyses of combinations of isoflavone intake and single nucleotide polymorphisms, an inverse association between intake and risk was limited to women with the GG genotype of the rs4986938 polymorphism for postmenopausal Japanese (odds ratio for highest versus lowest tertile = 0.47; P for trend = 0.01), Japanese Brazilians (odds ratio for highest versus lowest median = 0.31) and non-Japanese Brazilians (odds ratio for consumers versus non-consumers = 0.37) (P for interaction = 0.11, 0.08, and 0.21, respectively). We found no remarkable difference for the other four polymorphisms. Our findings suggest that polymorphisms in the estrogen receptor beta gene may modify the association between isoflavone intake and breast cancer risk.
    Cancer Science 03/2009; 100(5):927-33. DOI:10.1111/j.1349-7006.2009.01118.x · 3.52 Impact Factor
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    ABSTRACT: Most epidemiological studies of the association between breast cancer risk and exposure to organochlorine pesticides or polychlorinated biphenyls (PCBs), which are suspected endocrine disrupters and potential risk factors for human breast cancer, have been conducted in western countries, and the majority of results have been null and the rest inconsistent. Here, we examined these associations in Japanese women in the largest study in Asian women to date. The study was a matched case-control study of breast cancer with 403 eligible matched pairs from May 2001 to September 2005 at four hospitals in Nagano Prefecture, Japan. Serum samples were measured for PCBs and nine pesticide-related organochlorines, including dichlorodiphenyltrichloroethane (DDT). Odds ratios of breast cancer or its hormone-receptor-defined subtypes according to serum organochlorines were calculated. No increase in the risk of breast cancer was seen among women with higher serum concentrations of any organochlorine: o,p'-DDT, p,p'-DDT, p,p'-dichlorodiphenyldichloroethylene, hexachlorobenzene, beta-hexachlorocyclohexane, trans-nonachlor, cis-nonachlor, oxychlordane, mirex, or PCBs. Rather, higher serum levels of cis-nonachlor, mirex, or total PCBs were associated with a decreased risk of breast cancer Overall, these results suggest that breast cancer risk in Japan, a low-incidence country, is similar to that in western countries in terms of organochlorine exposure.
    Cancer Causes and Control 12/2008; 20(5):567-80. DOI:10.1007/s10552-008-9265-z · 2.74 Impact Factor
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    ABSTRACT: Cadmium may act like an estrogen and be a potential risk factor for estrogen-related diseases such as breast cancer and endometriosis. Here, we tested the hypothesis that higher cadmium exposure is associated with endometriosis among infertile Japanese women in a hospital-based case-control study. We recruited consecutive female patients aged 20-45 years who had complained of infertility and presented to a university hospital in Tokyo. The subjects were interviewed and provided a urine sample prior to a laparoscopic diagnosis of endometriosis between January 2000 and December 2001. The severity of endometriosis was then dichotomized into controls (stage 0 and I) and cases (stage II-IV). We finally measured urinary total cadmium concentration in 54 cases and 74 controls as a biomarker of long-term cumulative exposure. Odds ratios were adjusted for average menstrual cycle length, body-mass index and smoking status using unconditional logistic regression. Results showed no association between endometriosis and urinary cadmium concentration. Medians (interquartile ranges) of urinary cadmium concentration in cases and controls were 0.53 (0.40-0.73) and 0.54 (0.34-0.76) microg/g creatinine, respectively (P for difference=0.88). Adjusted odds ratio (95% confidence interval) for the highest versus lowest tertile of urinary creatinine-adjusted cadmium concentration was 0.86 (0.30 to 2.49, P for trend=0.79). Our results do not support the hypothesis that higher urinary cadmium concentration is associated with the risk of endometriosis.
    Science of The Total Environment 07/2008; 402(2-3):171-5. DOI:10.1016/j.scitotenv.2008.05.006 · 4.10 Impact Factor
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    ABSTRACT: A c. -285C >A single nucleotide polymorphism (SNP) in the promoter region of the E-cadherin (CDH1) gene, which is a tumor suppressor in gastric cancer (GC), has been shown to decrease gene transcription, but GC case-control studies of this SNP have yielded controversial results. A haplotype study in an Italian population showed that haplotypes based on three SNPs, including the c. -285C >A, are associated with susceptibility to GC. Hence, the purpose of the present study was to carry out a more comprehensive genetic analysis of CDH1 using haplotype-tagging SNPs (htSNPs) in a Japanese case-control study to identify the CDH1 haplotype associated with susceptibility to GC in a Japanese population. First, 11 SNPs in the CDH1 gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 30 healthy individuals. Haplotype frequencies were estimated with the expectation-maximization algorithm, and 7 common haplotypes of the CDH1 gene whose frequency was at least 3.3% were identified. Next, 5 htSNPs (c. -285C >A, c.48+6T >C, c.164 -3159T >C, c.2076C >T, and c.2296 -616G >C) were genotyped in a hospital-based case-control study of 148 GC patients and 292 age- and gender-matched healthy controls, and haplotype frequencies based on the 5 htSNPs were estimated. Although none of the 5 htSNPs was related to an overall risk of GC, frequencies of the ATCTG and CTTTG haplotypes were significantly higher and lower, respectively, in the GC cases than in the controls (p<0.05). These results suggest that the ATCTG and CTTTG CDH1 haplotypes may be associated with an increased risk and decreased risk, respectively, of GC in the Japanese population.
    Scandinavian Journal of Gastroenterology 01/2008; 42(12):1479-85. DOI:10.1080/00365520701478436 · 2.36 Impact Factor
  • Robert A Kanaly · Saburo Matsui · Tomoyuki Hanaoka · Tomonari Matsuda ·
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    ABSTRACT: Methods for determining the differential susceptibility of human organs to DNA damage have not yet been explored to any large extent due to technical constraints. The development of comprehensive analytical approaches by which to detect intertissue variations in DNA damage susceptibility may advance our understanding of the roles of DNA adducts in cancer etiology and as exposure biomarkers at least. A strategy designed for the detection and comparison of multiple DNA adducts from different tissue samples was applied to assess esophageal and peripherally- and centrally-located lung tissue DNA obtained from the same person. This adductome approach utilized LC/ESI-MS/MS analysis methods designed to detect the neutral loss of 2'-deoxyribose from positively ionized 2'-deoxynucleoside adducts transmitting the [M+H](+)>[M+H-116](+) transition over 374 transitions. In the final analyses, adductome maps were produced which facilitated the visualization of putative DNA adducts and their relative levels of occurrence and allowed for comprehensive comparisons between samples, including a calf thymus DNA negative control. The largest putative adducts were distributed similarly across the samples, however, differences in the relative amounts of putative adducts in lung and esophagus tissue were also revealed. The largest-occurring lung tissue DNA putative adducts were 90% similar (n=50), while putative adducts in esophagus tissue DNA were shown to be 80 and 84% similar to central and peripheral lung tissue DNA respectively. Seven DNA adducts, N(2)-ethyl-2'-deoxyguanosine (N(2)-ethyl-dG), 1,N(6)-etheno-2'-deoxyadenosine (varepsilondA), alpha-S- and alpha-R-methyl-gamma-hydroxy-1,N(2)-propano-2'-deoxyguanosine (1,N(2)-PdG(1), 1,N(2)-PdG(2)), 3-(2'-deoxyribosyl)-5,6,7,8-tetrahydro-8-hydroxy-pyrimido[1,2-a]purine-(3H)-one (8-OH-PdG) and the two stereoisomers of 3-(2'-deoxyribosyl)-5,6,7,8-tetrahydro-6-hydroxypyrimido[1,2-a]purine-(3H)-one (6-OH-PdG) were unambiguously detected in all tissue DNA samples by comparison to authentic adduct standards and stable isotope dilution and their identities were matched to putative adducts detected in the adductome maps.
    Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 12/2007; 625(1-2):83-93. DOI:10.1016/j.mrfmmm.2007.05.006 · 3.68 Impact Factor
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    ABSTRACT: Bisphenol A (BPA), a raw material commonly used in the manufacture of resins such as polycarbonate and epoxy, is a possible xenoestrogen that is hypothesized to disrupt the human endocrine system. Humans are widely exposed to BPA. We investigated the urinary concentration of BPA in infertile Japanese women and its possible association with endometriosis. We recruited 166 women (aged 20-45) who had complained of infertility and visited a university hospital in Tokyo. The subjects were interviewed and their urine samples were obtained prior to a laparoscopic diagnosis of endometriosis between January 2000 and December 2001. Urinary total BPA concentration in 140 eligible urine samples was then measured using enzymatic deconjugation of glucuronide and sulfate and high-performance liquid chromatography isotope-dilution tandem mass spectrometry. Median (25th-75th percentile) unadjusted and creatinine-adjusted urinary BPA concentrations were 1.6 (0.69-2.8) μg/L and 0.80 (0.45-1.3) μg/g creatinine. No significant monotonic association of endometriosis with urinary BPA concentration was observed. Median urinary BPA concentration in women with stage 0-1 endometriosis (0.74 μg/g creatinine) did not significantly differ from that in those with stage II-IV endometriosis (0.93 μg/g creatinine) (p for difference=0.24). This study, based on a larger number of samples than those in previous studies in Japan and using the most reliable analytical method currently available, showed that urinary concentrations of BPA in women who consulted a physician for infertility were not higher than those in other populations. Moreover, no association between urinary BPA concentration and endometriosis was found in this cross-sectional study.
    Environmental Health and Preventive Medicine 11/2007; 12(6):258-64. DOI:10.1007/BF02898033
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    ABSTRACT: Helicobacter pylori is a major risk factor for atrophic gastritis and gastric cancer. Various extragastric manifestations of H. pylori infection have also recently been suggested. However, the correlation between H. pylori and colorectal cancer (CRC) is controversial. The aim of this study was to examine the correlation between H. pylori, serum gastrin level, and atrophic gastritis with CRC. Subjects were patients with CRC; controls were participants of a health check-up program that was conducted between October 1998 and March 2002 at four hospitals in Nagano Prefecture. For 121 newly diagnosed CRC cases, two controls matched by age (within 3 years), gender, and residence were randomly selected from the program participants. We conducted questionnaires and obtained blood samples from the cases and their controls. Consequently, the CRC cancer pairs consisted of 113 cases and 226 controls. Neither H. pylori infection nor gastrin level nor atrophic gastritis showed any association with a risk for CRC. However, serologically determined atrophic gastritis demonstrated significant elevation in odds ratios (ORs) for rectal cancer (OR = 3.15, 95% confidence interval; 1.19-8.35). Gastric conditions such as chronic H. pylori infection and atrophic gastritis are unlikely to increase the risk for CRC, although atrophic gastritis may increase the risk of rectal cancer.
    Helicobacter 09/2007; 12(4):328-32. DOI:10.1111/j.1523-5378.2007.00513.x · 4.11 Impact Factor
  • Minatsu Kobayashi · Tomoyuki Hanaoka · Shoichiro Tsugane ·
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    ABSTRACT: Several case-control studies have reported possible associations between heterocyclic amine (HCA) intake and the risk of cancer. The validity of questionnaires used to assess HCA intake has hardly been examined, however; in particular, no biomarker able to serve as an independent measure of habitual HCA intake has been established. In this study, we examined the validity of HCA intake estimated from a food frequency questionnaire (FFQ) using 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) level in hair as a reference method. Study subjects were 20 volunteers (7 men and 13 women) aged 25-57 years residing in Tokyo or neighboring cities in Japan. The subjects completed the FFQ, and gave 3-5g of hair twice at an interval of 1-3 months for use in establishing validity. Results showed that intakes of PhIP, MeIQ, Trp-P-1, and total HCA by the FFQ were significantly correlated with PhIP levels in hair when adjustment was made for melanin content (r=0.47, r=0.50, r=0.55, and r=0.51, respectively). The present study indicates that HCA intake estimated from this FFQ provides a reasonable ranking of individuals to allow the analysis of associations between HCA intake and risk of cancer in large-scale epidemiological studies.
    Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 06/2007; 630(1-2):14-9. DOI:10.1016/j.mrgentox.2007.02.003 · 3.68 Impact Factor
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    ABSTRACT: Progression of endometriosis is considered estrogen-dependent. Dietary soy isoflavones may affect the risk of endometriosis, and polymorphisms in estrogen receptor genes may modify this association. We examined associations among soy isoflavone intake, estrogen receptor 2 (ESR2) gene polymorphisms and risk of endometriosis. We recruited women age 20-45 years old who had consulted a university hospital for infertility in Tokyo, Japan in 1999 or 2000. A total of 138 eligible women were diagnosed laparoscopically and classified into 3 subgroups: control (no endometriosis), early endometriosis (stage I-II) and advanced endometriosis (stage III-IV). We measured urinary levels of genistein and daidzein as markers for dietary intake of soy isoflavones, and genotyped ESR2 gene RsaI polymorphisms. Higher levels of urinary genistein and daidzein were associated with decreased risk of advanced endometriosis (P for trend = 0.01 and 0.06, respectively) but not early endometriosis. For advanced endometriosis, the adjusted odds ratio for the highest quartile group was 0.21 (95% confidence interval = 0.06-0.76) for genistein and 0.29 (0.08-1.03) for daidzein, when compared with the lowest group. Inverse associations were also noted between urinary isoflavones and the severity of endometriosis (P for trend = 0.01 for genistein and 0.07 for daidzein). For advanced endometriosis, ESR2 gene RsaI polymorphism appeared to modify the effects of genistein (P for interaction = 0.03). Dietary isoflavones may reduce the risk of endometriosis among Japanese women.
    Epidemiology 06/2007; 18(3):402-8. DOI:10.1097/01.ede.0000257571.01358.f9 · 6.20 Impact Factor
  • Robert A. Kanaly · Saburo Matsui · Tomoyuki Hanaoka · Tomonari Matsuda ·

    Meeting of the Division of Chemical Toxicology of the; 12/2006

  • Environmental Health Perspectives 11/2006; 114(11). DOI:10.1289/ehp.9016 · 7.98 Impact Factor
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    ABSTRACT: Observations of adverse developmental and reproductive effects in laboratory animals and wildlife have fueled increasing public concern regarding the potential for various chemicals to impair human fertility. Our objective in this study was to assess the effect of occupational exposure to high levels of phthalate esters on the balance of gonadotropin and gonadal hormones including luteinizing hormone, follicle-stimulating hormone, free testosterone (fT), and estradiol. We examined urine and blood samples of 74 male workers at a factory producing unfoamed polyvinyl chloride flooring exposed to di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) and compared them with samples from 63 male workers from a construction company, group matched for age and smoking status. Compared to the unexposed workers, the exposed workers had substantially and significantly elevated concentrations of mono-n-butyl phthalate (MBP; 644.3 vs. 129.6 microg/g creatinine, p < 0.001) and mono-2-ethylhexyl phthalate (MEHP; 565.7 vs. 5.7 microg/g creatinine, p < 0.001). fT was significantly lower (8.4 vs. 9.7 microg/g creatinine, p = 0.019) in exposed workers than in unexposed workers. fT was negatively correlated to MBP (r = -0.25, p = 0.03) and MEHP (r = -0.19, p = 0.095) in the exposed worker group. Regression analyses revealed that fT decreases significantly with increasing total phthalate ester score (the sum of quartiles of MBP and MEHP; r = -0.26, p = 0.002). We observed a modest and significant reduction of serum fT in workers with higher levels of urinary MBP and MEHP compared with unexposed workers.
    Environmental Health Perspectives 11/2006; 114(11):1643-8. · 7.98 Impact Factor
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    ABSTRACT: Although adequate assessment of exposure is needed in epidemiological studies among foundry workers, previous studies are often lacking in this aspect. We conducted a retrospective cohort study of a Chinese iron and steel company with a 14-yr follow up during 1980-1993. Exposure assessment was performed for a single job, i.e., the current job for the active worker and the longest job for the retired or deceased worker as of the end of the follow-up, which was allocated as the surrogate of lifetime job and was applied to a job-exposure matrix. Of the 147,062 cohort members, 52,394 males (43%) and 5,291 females (21%) were exposed to any of 15 hazardous factors such as dust, silica, PAHs (polycyclic aromatic hydrocarbons), CO (carbon monoxide) and heat. In 2,104 randomly selected samples, the exposure assessment of exposed workers based on a single job was found to be 12-14% lower than the real situation. This study suggests that the exposure assessment is valuable in evaluating the health effects among the foundry workers, despite some limitations such as underestimation of exposure assessment and the lack of data regarding smoking and drinking habits.
    Journal of UOEH 10/2006; 28(3):253-63.

Publication Stats

2k Citations
234.37 Total Impact Points


  • 2011-2013
    • Showa University
      Shinagawa, Tōkyō, Japan
  • 1992-2010
    • National Cancer Center, Japan
      • Research Center for Cancer Prevention and Screening
      Edo, Tokyo, Japan
  • 2006
    • Kyoto University
      Kioto, Kyōto, Japan
    • University of Occupational and Environmental Health
      • Department of Environmental Epidemiology
      Kitakyūshū, Fukuoka, Japan
  • 2000-2004
    • National Cancer Research Institute
      Londinium, England, United Kingdom
  • 2002
    • Hospital Santa Cruz
      San Paulo, São Paulo, Brazil
  • 1996-1999
    • Institute for Science of Labour
      Edo, Tōkyō, Japan