Associations between metal concentrations in whole blood and placenta previa and placenta accreta: the Japan Environment and Children's Study (JECS)

BACKGROUND@#Placenta previa and placenta accreta associate with high morbidity and mortality for both mothers and fetus. Metal exposure may have relationships with placenta previa and placenta accreta. This study analyzed the associations between maternal metal (cadmium [Cd], lead [Pb], mercury [Hg], selenium [Se], and manganese [Mn]) concentrations and placenta previa and placenta accreta.@*METHODS@#We recruited 17,414 women with singleton pregnancies. Data from a self-administered questionnaire regarding the first trimester and medical records after delivery were analyzed. Maternal blood samples were collected to measure metal concentrations. The subjects were classified into four quartiles (Q1, Q2, Q3, and Q4) according to metal concentrations.@*RESULTS@#The odds ratio for placenta previa was significantly higher among subjects with Q4 Cd than those with Q1 Cd. The odds ratio for placenta previa was significantly higher for subjects with Q2 Pb than those with Q1 Pb.@*CONCLUSION@#Participants with placenta previa had higher Cd concentrations. However, this study was cross-sectional and lacked important information related to Cd concentration, such as detailed smoking habits and sources of Cd intake. In addition, the subjects in this study comprised ordinary pregnant Japanese women, and it was impossible to observe the relationship between a wide range of Cd exposure and placenta previa. Therefore, epidemiological and experimental studies are warranted to verify the relationship between Cd exposure and pregnancy abnormalities.

Questionnaire results on exposure characteristics of pregnant women participating in the Japan Environment and Children Study (JECS)

BACKGROUND@#The Japan Environment and Children's Study (JECS) is a nation-wide birth cohort study investigating environmental effects on children's health and development. In this study, the exposure characteristics of the JECS participating mothers were summarized using two questionnaires administered during pregnancy.@*METHODS@#Women were recruited during the early period of their pregnancy. We intended to administer the questionnaire during the first trimester (MT1) and the second/third trimester (MT2). The total number of registered pregnancies was 103,099.@*RESULTS@#The response rates of the MT1 and MT2 questionnaires were 96.8% and 95.1%, respectively. The mean gestational ages (SDs) at the time of the MT1 and MT2 questionnaire responses were 16.4 (8.0) and 27.9 (6.5) weeks, respectively. The frequency of participants who reported "lifting something weighing more than 20 kg" during pregnancy was 5.3% for MT1 and 3.9% for MT2. The Cohen kappa scores ranged from 0.07 to 0.54 (median 0.31) about the occupational chemical use between MT1 and MT2 questionnaires. Most of the participants (80%) lived in either wooden detached houses or steel-frame collective housing. More than half of the questionnaire respondents answered that they had "mold growing somewhere in the house". Insect repellents and insecticides were used widely in households: about 60% used "moth repellent for clothes in the closet," whereas 32% applied "spray insecticide indoors" or "mosquito coil or an electric mosquito repellent mat."@*CONCLUSIONS@#We summarized the exposure characteristics of the JECS participants using two maternal questionnaires during pregnancy.

Association between time-related work factors and dietary behaviors: results from the Japan Environment and Children's Study (JECS)

BACKGROUND@#Few studies have examined the association of workhours and shift work (referred to here as "time-related work factors") with dietary behaviors. We aimed to investigate this association, as well as the dietary behaviors among individuals with occupations characterized by time-related work factors.@*METHODS@#A cross-sectional study was performed using data from the Japan Environment and Children's Study. The study included 39,315 working men. Dietary behaviors (i.e., skipping breakfast, eating out, eating instant food, overeating, and eating fast) were assessed with a self-reported information from the Food Frequency Questionnaire. Logistic regression analysis was conducted to examine the associations of time-related work factors with dietary behaviors and dietary behavior tendencies among those in occupations characterized by long workhours and/or shift work.@*RESULTS@#Long workhours were associated with high frequencies of skipping breakfast, eating out, eating instant food, overeating, and eating fast. The frequency of having shift work was associated with high frequencies of skipping breakfast, eating out, and eating instant food. Several occupations involving long workhours and/or shift work showed specific dietary behaviors; in some occupations, the level of significance changed after adjusting for time-related work factors in addition to other potential confounding factors.@*CONCLUSIONS@#Time-related work factors may help explain workers' dietary behaviors. Long workhours and shift work may lead to poor dietary behaviors. Other factors influenced by occupation itself, such as food environment, may also influence workers' dietary behaviors. Workhours and/or shift work, and these other work factors, should be given attention in workplace health promotion.

Evaluation of chemical-specific IgG antibodies in male workers from a urethane foam factory

BACKGROUND@#Plastic resins are complex chemicals that contain toluene diisocyanate (TDI) and/or trimellitic anhydride (TMA), which cause occupational allergies (OA), including respiratory allergies. Serum IgGs against TDI and TMA have been suggested as potential markers of the exposure status and as exploring cause of OA. Although TDI-specific IgG has been examined for suspected OA, TMA-specific IgG is not commonly evaluated in a urethane foam factory. This study therefore investigated both TDI- and TMA-specific IgGs in suspected OA patients and to evaluate the usefulness of the measurement of multiple chemical-specific IgG measurement for practical monitoring.@*METHODS@#Blood samples were collected from two male workers who developed respiratory allergies supposedly caused by occupational exposure to TDI and/or TMA for the presence of TDI- and TMA-specific IgGs. In addition, blood samples from 75 male workers from a urethane foam factory, along with 87 male control subjects, were collected in 2014 and tested for the same IgGs in 2014. The presence and levels of TDI- and TMA-specific serum IgGs were measured using dot blot assays.@*RESULTS@#We found that controls had mean concentrations of TDI- and TMA-specific IgGs of 0.98 and 2.10 μg/mL, respectively. In the two workers with respiratory allergies, the TDI-specific IgG concentrations were 15.6 and 9.51 μg/mL, and TMA-specific IgG concentrations were 4.56 and 14.4 μg/mL, which are clearly higher than those in controls. Mean concentrations of TDI- and TMA-specific IgGs in the factory workers were 1.89 and 2.41 μg/mL, respectively, and are significantly higher than those of the controls (P < 0.001 and P < 0.026 for TDI- and TMA-specific IgGs, respectively).@*CONCLUSION@#The workers suspected of OA showed an evidently high level of TDI- and TMA-specific IgG, and these levels in workers at the urethane foam factory were also significantly higher than those in controls. In conclusion, the measurement of TDI- and TMA-specific IgG among workers using plastic resins is helpful to monitor their exposure status.

International Comparison of Criteria for Evaluating Sensitization of PRTR-Designated Chemical Substances

In this study, we aim to compare the criteria for sensitizers among national organizations in various countries and international organizations, and to specify whether each Pollutant Release and Transfer Register (PRTR)-designated chemical substance is a sensitizer by each organization. The definition of sensitizing chemicals and the designation of respective sensitizers according to the PRTR law, Japan Society for Occupational Health (JSOH), American Conference of Governmental Industrial Hygienists (ACGIH), European Union (EU), and Deutsche Forschungsgemeinshaft (DFG) were studied. Of the 435 PRTR-designated chemical substances, 15 are listed as sensitizers according to the PRTR law, 16 as sensitizers of the airway and 21 as sensitizers of the skin by JSOH, 12 as sensitizers (no discrimination) by ACGIH, 19 (airway) and 85 (skin) by EU, and 15 (airway) and 43 (skin) by DFG. Only 9 substances were designated as sensitizers by all these organizations. The variation in the designation of sensitizers is accounted for by the differences in the classification criteria and grouping of chemical substances. JSOH limits the definition of sensitizers to substances that induce allergic reactions in humans and uses only human data. Other organizations utilize not only human evidence but also appropriate animal tests. In addition, EU designates an isocyanate as a sensitizer except those for which there is evidence showing that they do not cause respiratory sensitivity. The worldwide enforcement of the globally harmonized system (GHS) of classification and labeling of chemicals could promote not only the consistent designation of sensitizers among national and international organizations, but also the development of testing guidelines and classification criteria for mixtures.

International comparison of criteria for evaluating sensitization of PRTR-designated chemical substances

In this study, we aim to compare the criteria for sensitizers among national organizations in various countries and international organizations, and to specify whether each Pollutant Release and Transfer Register (PRTR)-designated chemical substance is a sensitizer by each organization. The definition of sensitizing chemicals and the designation of respective sensitizers according to the PRTR law, Japan Society for Occupational Health (JSOH), American Conference of Governmental Industrial Hygienists (ACGIH), European Union (EU), and Deutsche Forschungsgemeinshaft (DFG) were studied. Of the 435 PRTR-designated chemical substances, 15 are listed as sensitizers according to the PRTR law, 16 as sensitizers of the airway and 21 as sensitizers of the skin by JSOH, 12 as sensitizers (no discrimination) by ACGIH, 19 (airway) and 85 (skin) by EU, and 15 (airway) and 43 (skin) by DFG. Only 9 substances were designated as sensitizers by all these organizations. The variation in the designation of sensitizers is accounted for by the differences in the classification criteria and grouping of chemical substances. JSOH limits the definition of sensitizers to substances that induce allergic reactions in humans and uses only human data. Other organizations utilize not only human evidence but also appropriate animal tests. In addition, EU designates an isocyanate as a sensitizer except those for which there is evidence showing that they do not cause respiratory sensitivity. The worldwide enforcement of the globally harmonized system (GHS) of classification and labeling of chemicals could promote not only the consistent designation of sensitizers among national and international organizations, but also the development of testing guidelines and classification criteria for mixtures.

Evidence-Based Prevention (EBP): A Review of Cytochrome P450 Expression in the Bronchial Epithelium and New Approach to Lung Cancer Prevention

The number of fatalities in Japan attributable to lung cancer exceeded 50000 in 2001. It is socially desirable that various markers, which can be utilized for the prevention of lung cancer, be established. We believe that smoking or exposure to carcinogens in air induces mutations in bronchial and alveolar epithelia, leading to the development of lung cancer. It would be useful to have markers of individual differences in susceptibility to chemical carcinogen-induced lung cancer 1) to identify genetic polymorphisms of enzymes metabolizing chemical carcinogens and 2) to investigate the expression of enzymes metabolizing chemical carcinogens. In this paper, we review CYP expression in the bronchial epithelium. CYP1, CYP2 and CYP3 are expressed in the bronchial epithelium. We also show the relationship between the genetic polymorphisms of cytochrome P450 (CYP) and a person’s susceptibility to chemical carcinogen-induced lung cancer. We demonstrate the relationship between cigarette consumption and the CYP expression profile in the bronchial epithelium. To maintain and promote public health, we must apply evidence, such as CYP polymorphisms and CYP profiles to disease prevention and also to aggressively advance evidence-based prevention (EBP) of lung cancer.

Evidence-based prevention (EBP): A review of cytochrome P450 expression in the bronchial epithelium and new approach to lung cancer prevention

The number of fatalities in Japan attributable to lung cancer exceeded 50000 in 2001. It is socially desirable that various markers, which can be utilized for the prevention of lung cancer, be established. We believe that smoking or exposure to carcinogens in air induces mutations in bronchial and alveolar epithelia, leading to the development of lung cancer. It would be useful to have markers of individual differences in susceptibility to chemical carcinogen-induced lung cancer 1) to identify genetic polymorphisms of enzymes metabolizing chemical carcinogens and 2) to investigate the expression of enzymes metabolizing chemical carcinogens. In this paper, we review CYP expression in the bronchial epithelium. CYP1, CYP2 and CYP3 are expressed in the bronchial epithelium. We also show the relationship between the genetic polymorphisms of cytochrome P450 (CYP) and a person's susceptibility to chemical carcinogen-induced lung cancer. We demonstrate the relationship between cigarette consumption and the CYP expression profile in the bronchial epithelium. To maintain and promote public health, we must apply evidence, such as CYP polymorphisms and CYP profiles to disease prevention and also to aggressively advance evidence-based prevention (EBP) of lung cancer.

Lung cancer andCYP1A1 orGSTM1 polymorphisms

Most chemical carcinogens are metabolized and activated in vivo by phase I enzymes including the microsomal cytochromes P450 and epoxide hydroxylases. The carcinogens and their metabolites are detoxified by phase II enzymes that in clude various transferases such as glutathion-S-transferases (GST). Increasing numbers of studies have demonstrated the association of the polymorphisms inGSTM1 (a member of GST) andCYP1A1 genes with the susceptibility to lung cancer. Subsequently, the polymorphisms appear to be important biomarkers that provide information for assessment of exposure and total burden of environmental carcinogens. Therefore, the investigation of the polymorphisms in these genes will provide information not only for the prediction of individual cancer risk but also for the prevention of cancer. In this review, we will summarize the polymorphisms in theGSTM1 andCYP1A1 genes and their relation to lung cancer susceptibility.

Genetic polymorphisms ofCYP2A6 andCYP2E1 with tobacco smoking is not associated with risk of urothelial cancer

<p><b>OBJECTIVES</b>To elucidate the association between genetic polymorphisms ofCYP2a6 andCYP2E1 and urothelial cancer susceptibility.</p><p><b>METHODS</b>A total of 137 Japanese patients with urothelial cancer and 217 Japanese healthy controls, frequency-matched for age and gender, were selected. The polymorphisms ofCYP2A6 andCYP2E1 were analyzed by PCR-RFLP, and cigarette smoking histories were obtained through interviews</p><p><b>RESULTS</b>The frequency ofCYP2A6 homozygote deletion genotype was 2.9% in the patients, compared with 3.2% in the controls (OR=0.84, 95% CI 0.24-2.96). The frequencies ofCYP2E1 C1/c2 andC2/c2 were 27.7% and 4.4% in the patients, compared with 35.5% and 6.0% in the controls (OR=0.68, 95% CI 0.42-1.09, OR=0.67, 95% CI 0.24-1.84, respectively). No statistically significant differences were observed when theCYP2A6 homozygote deletion genotype and theCYP2E1 genotypes were examined relative to smoking status.</p><p><b>CONCLUSIONS</b>Our data indicate that neither a relationship between genetically impaired nitrosamine metabolism and tobacco-smoking consumption, nor urothelial cancer risk related to theCYP2A6 deletion genotype andCYP2E1 Rsa I genotype was found in Japanese population.</p>

Lung Cancer and \it{CYP1A1} or \it{GSTM1} Polymorphisms

Most chemical carcinogens are metabolized and activated in vivo by phase I enzymes including the microsomal cytochromes P450 and epoxide hydroxylases. The carcinogens and their metabolites are detoxified by phase II enzymes that include various transferases such as glutathion-S-transferases (GST). Increasing numbers of studies have demonstrated the association of the polymorphisms in GSTM1 (a member of GST) and CYP1A1 genes with the susceptibility to lung cancer. Subsequently, the polymorphisms appear to be important biomarkers that provide information for assessment of exposure and total burden of environmental carcinogens. Therefore, the investigation of the polymorphisms in these genes will provide information not only for the prediction of individual cancer risk but also for the prevention of cancer. In this review, we will summarize the polymorphisms in the GSTM1 and CYP1A1 genes and their relation to lung cancer susceptibility.

Genetic Polymorphisms of \it{CYP2A6} and \it{CYP2E1} with Tobacco Smoking is not Associated with Risk of Urothelial Cancer

Objectives: To elucidate the association between genetic polymorphisms of CYP2A6 and CYP2E1 and urothelial cancer susceptibility. Methods: A total of 137 Japanese patients with urothelial cancer and 217 Japanese healthy controls, frequency-matched for age and gender, were selected. The polymorphisms of CYP2A6 and CYP2E1 were analyzed by PCR-RFLP, and cigarette smoking histories were obtained through interviews. Results: The frequency of CYP2A6 homozygote deletion genotype was 2.9% in the patients, compared with 3.2% in the controls (OR=0.84, 95% CI 0.24−2.96). The frequencies of CYP2E1 C1/c2 and C2/c2 were 27.7% and 4.4% in the patients, compared with 35.5% and 6.0% in the controls (OR=0.68, 95% CI 0.42 −1.09, OR=0.67, 95% CI 0.24−1.84, respectively). No statistically significant differences were observed when the CYP2A6 homozygote deletion genotype and the CYP2E1 genotypes were examined relative to smoking status. Conclusions: Our data indicate that neither a relationship between genetically impaired nitrosamine metabolism and tobacco-smoking consumption, nor urothelial cancer risk related to the CYP2A6 deletion genotype and CYP2E1 Rsa I genotype was found in Japanese population.