Sub-multiplicative interaction between polygenic risk score and household coal use in relation to lung adenocarcinoma among never-smoking women in Asia.

We previously identified 10 lung adenocarcinoma susceptibility loci in a genome-wide association study (GWAS) conducted in the Female Lung Cancer Consortium in Asia (FLCCA), the largest genomic study of lung cancer among never-smoking women to date. Furthermore, household coal use for cooking and heating has been linked to lung cancer in Asia, especially in Xuanwei, China. We investigated the potential interaction between genetic susceptibility and coal use in FLCCA. We analyzed GWAS-data from Taiwan, Shanghai, and Shenyang (1472 cases; 1497 controls), as well as a separate study conducted in Xuanwei (152 cases; 522 controls) for additional analyses. We summarized genetic susceptibility using a polygenic risk score (PRS), which was the weighted sum of the risk-alleles from the 10 previously identified loci. We estimated associations between a PRS, coal use (ever/never), and lung adenocarcinoma with multivariable logistic regression models, and evaluated potential gene-environment interactions using likelihood ratio tests. There was a strong association between continuous PRS and lung adenocarcinoma among never coal users (Odds Ratio (OR) = 1.69 (95% Confidence Interval (CI) = 1.53, 1.87), p=1 × 10-26). This effect was attenuated among ever coal users (OR = 1.24 (95% CI: 1.03, 1.50), p = 0.02, p-interaction = 6 × 10-3). We observed similar attenuation among coal users from Xuanwei. Our study provides evidence that genetic susceptibility to lung adenocarcinoma among never-smoking Asian women is weaker among coal users. These results suggest that lung cancer pathogenesis may differ, at least partially, depending on exposure to coal combustion products. Notably, these novel findings are among the few instances of sub-multiplicative gene-environment interactions in the cancer literature.

Association between polymorphisms in pre-miRNA genes and risk of lung cancer in a Chinese non-smoking female population.

BACKGROUND: MicroRNAs play important roles in the development of human chronic diseases including lung cancer. This is the first case-control study of lung cancer in a non-smoking female population in northeast China, to evaluate the roles of the polymorphisms in pre-miRNAs on risk of lung cancer. METHODS: The genotypes of six polymorphisms in miRNAs were determined in 575 patients with lung cancer and 608 healthy controls who were frequency matched for age. RESULTS: For miR-146a rs2910164, individuals carrying heterozygous CG or homozygous GG genotype had decreased risks of lung cancer compared with those carrying homozygous wild CC genotype (adjusted odds ratios were 0.76 and 0.64, 95% confidence intervals were 0.59-0.99 and 0.46-0.90, P values were 0.039 and 0.010, respectively). G allele of rs2910164 was associated with a lower risk of lung cancer with a significant odds ratio of 0.80. MiR-423 rs6505162CA or AA genotype was associated with significantly decreased risk for lung cancer compared to CC genotype (adjusted odds ratios were 0.77 and 0.54). The significant result was also found in the allele model with odds ratio of 0.75. However, miR-196a2 rs11614913, miR-30c-1 rs928508, miR-608 rs4919510 and miR-27a rs895819 polymorphisms were not significantly associated with lung cancer risks in any models. The similar results were also found in lung adenocarcinoma patients. CONCLUSIONS: These findings suggest that miR-146a rs2910164C>G and miR-423 rs6505162C>A polymorphisms may contribute to genetic susceptibility to lung cancer and lung adenocarcinoma in Chinese non-smoking females.

Association of urine CC16 and lung function and asthma in Chinese children.

BACKGROUND: Many studies have shown the relationship between serum Club cell secretory protein-16 (CC16) and respiratory diseases. However, little research has been done to study urinary CC16 in relation to respiratory diseases. Our objective was to examine the association of urinary CC16 and physician-diagnosed asthma or lung function measurements in Chinese children. METHODS: A total of 147 physician-diagnosed children with asthma, ages 9-15 years, were recruited from our cross-sectional study population in northeast China. The 390 healthy children who were not asthmatic and not smokers were selected at random from the population according to 10% proportional sampling. Lung function values, including forced expiratory volume in 1 second and forced vital capacity were measured with two portable spirometers. Urine CC16 was determined by using an enzyme-link immunoassay kit. The relationships between urine CC16 levels and asthma, lung function were assessed by multiple regression models. RESULTS: The geometric mean (95% confidence interval [CI]) creatinine-adjusted urine CC16 level was, for creatinine, 9.77 ng/mg (95% CI, 8.12-12.02 ng/mg). After adjustments for sex, age, body mass index, parental education, and smoking status, lower urine CC16 levels were found to be associated with asthma (odds ratio 0.782 [95% CI, 0.617- 0.990]). A positive association was found between urine CC16 and forced vital capacity (beta 0.064 [95% CI, 0.008-0.119]). CONCLUSION: Our study demonstrated lower levels of urine CC16 and lung function in patients with asthma than in those patients without asthma. CC16 in urine may be a useful tool or biomarker for investigating lung epithelium integrity among children with asthma or lung injury.

Interaction between Polymorphisms in Pre-MiRNA Genes and Cooking Oil Fume Exposure on the Risk of Lung Cancer in Chinese Non-Smoking Female Population.

BACKGROUND: Both genetic polymorphisms and environmental risk factors play important roles in the development of human chronic diseases including lung cancer. This is the first case-control study of interaction between polymorphisms in pre-miRNA genes and cooking oil fume exposure on the risk of lung cancer. METHODS: A hospital-based case-control study of 258 cases and 310 controls was conducted. Six polymorphisms in miRNAs were determined by Taqman allelic discrimination method. The gene-environment interactions were assessed on both additive and multiplicative scale. The statistical analyses were performed mostly with SPSS. RESULTS: The combination of the risk genotypes of five miRNA SNPs (miR-146a rs2910164, miR-196a2 rs11614913, miR-608 rs4919510, miR-27a rs895819 and miR-423 rs6505162) with risk factor (cooking oil fume exposure) contributed to a significantly higher risk of lung cancer, and the corresponding ORs (95% confidence intervals) were 1.91(1.04-3.52), 1.94 (1.16-3.25), 2.06 (1.22-3.49), 1.76 (1.03-2.98) and 2.13 (1.29-3.51). The individuals with both risk genotypes of miRNA SNPs and exposure to risk factor (cooking oil fumes) were in a higher risk of lung cancer than persons with only one of the two risk factors (ORs were 1.91, 1.05 and 1.41 for miR-146a rs2910164, ORs were 1.94, 1.23 and 1.34 for miR-196a2 rs11614913, ORs were 2.06, 1.41 and 1.68 for miR-608 rs4919510, ORs were 1.76, 0.82 and 1.07 for miR-27a rs895819, and ORs were 2.13, 1.15 and 1.02 for miR-423 rs6505162, respectively). All the measures of biological interaction indicate that there were not indeed biological interactions between the six SNPs of miRNAs and exposure to cooking oil fumes on an additive scale. Logistic models suggested that the gene-environment interactions were not statistically significant on a multiplicative scale. CONCLUSIONS: The interactions between miRNA SNPs and cooking oil fume exposure suggested by ORs of different combination were not statistically significant.

Interactions between household air pollution and GWAS-identified lung cancer susceptibility markers in the Female Lung Cancer Consortium in Asia (FLCCA).

We previously carried out a multi-stage genome-wide association study (GWAS) on lung cancer among never smokers in the Female Lung Cancer Consortium in Asia (FLCCA) (6,609 cases, 7,457 controls) that identified novel susceptibility loci at 10q25.2, 6q22.2, and 6p21.32, and confirmed two previously identified loci at 5p15.33 and 3q28. Household air pollution (HAP) attributed to solid fuel burning for heating and cooking, is the leading cause of the overall disease burden in Southeast Asia, and is known to contain lung carcinogens. To evaluate the gene-HAP interactions associated with lung cancer in loci independent of smoking, we analyzed data from studies participating in FLCCA with fuel use information available (n = 3; 1,731 cases; 1,349 controls). Coal use was associated with a 30% increased risk of lung cancer (OR 1.3, 95% CI 1.0-1.6). Among the five a priori SNPs identified by our GWAS, two showed a significant interaction with coal use (HLA Class II rs2395185, p = 0.02; TP63 rs4488809 (rs4600802), p = 0.04). The risk of lung cancer associated with coal exposure varied with the respective alleles for these two SNPs. Our observations provide evidence that genetic variation in HLA Class II and TP63 may modify the association between HAP and lung cancer risk. The roles played in the cell cycle and inflammation pathways by the proteins encoded by these two genes provide biological plausibility for these interactions; however, additional replication studies are needed in other non-smoking populations.

Genetic polymorphisms of TERT and CLPTM1L, cooking oil fume exposure, and risk of lung cancer: a case-control study in a Chinese non-smoking female population.

Genetic polymorphisms of telomerase reverse transcriptase (TERT) and cleft lip and palate transmembrane 1-like (CLPTM1L) genes in chromosome 5p15.33 region were previously identified to influence the risks of lung cancer. This study aimed to investigate the association between polymorphisms in TERT and CLPTM1L genes with the risk of lung cancer, as well as the interaction of the polymorphisms and the environmental risk factors in Chinese non-smoking females. A hospital-based case-control study of 524 cases and 524 controls was conducted. Two polymorphisms were determined by Taqman allelic discrimination method. The statistical analyses were performed mostly with SPSS. This study showed that the individuals with the TG or GG genotypes of TERT polymorphism (rs2736100) were at an increased risk for lung cancer compared with those carrying the TT genotype in Chinese non-smoking females [adjusted odds ratios (ORs) were 1.44 and 1.85, 95 % confidence intervals (CIs) were 1.09-1.90 and 1.29-2.65, respectively]. The stratified analysis suggested that increased risks were more pronounced in lung adenocarcinoma (corresponding ORs were 1.71 and 2.30, 95 % CIs were 1.25-2.35 and 1.54-3.43). Our results showed that exposure to cooking oil fume was associated with increased risk of lung cancer in Chinese non-smoking females (adjusted ORs 1.59, 95 % CI 1.13-2.23). However, we did not observe a significant interaction of cooking oil fume and TERT polymorphism on lung cancer among Chinese non-smoking females. TERT polymorphism (rs2736100) might be a genetic susceptibility factor for lung cancer in non-smoking females in China.

TP63 gene polymorphisms, cooking oil fume exposure and risk of lung adenocarcinoma in Chinese non-smoking females.

BACKGROUND: Genetic polymorphisms of TP63 have been suggested to influence susceptibility to lung adenocarcinoma development in East Asian populations. This study aimed to investigate the relationship between common polymorphisms in the TP63 gene and the risk of lung adenocarcinoma, as well as interactions of the polymorphisms with environmental risk factors in Chinese non-smoking females. METHODS: A case-control study of 260 cases and 318 controls was conducted. Data concerning demographic and risk factors were obtained for each subject. The genetic polymorphisms were determined by Taqman real-time PCR and statistical analyses were performed using SPSS software. RESULTS: For 10937405, carriers of the CT genotype or at least one T allele (CT/TT) had lower risks of lung adenocarcinoma compared with the homozygous wild CC genotype in Chinese nonsmoking females (adjusted ORs were 0.68 and 0.69, 95%CIs were 0.48-0.97 and 0.50-0.97, P values were 0.033 and 0.030, respectively). Allele comparison showed that the T allele of rs10937405 was associated with a decreased risk of lung adenocarcinoma with an OR of 0.78 (95%CI=0.60-1.01, P=0.059). Our results showed that exposure to cooking oil fumes was associated with increased risk of lung adenocarcinoma in Chinese nonsmoking females (adjusted OR=1.58, 95%CI=1.11-2.25, P=0.011). However, we did not observe a significant interaction of cooking oil fumes and TP63 polymorphisms. CONCLUSION: TP63 polymorphism might be a genetic susceptibility factor for lung adenocarcinoma in Chinese non-smoking females, but no significant interaction was found with cooking oil fume exposure.

Effects of outdoor and indoor air pollution on respiratory health of Chinese children from 50 kindergartens.

BACKGROUND: Concentrations of ambient air pollution and pollutants in China have changed considerably during the last decade. However, few studies have evaluated the effects of current ambient air pollution on the health of kindergarten children. METHODS: We studied 6730 Chinese children (age, 3-7 years) from 50 kindergartens in 7 cities of Northeast China in 2009. Parents or guardians completed questionnaires that asked about the children's histories of respiratory symptoms and risk factors. Three-year concentrations of particles with an aerodynamic diameter ≤10 µm (PM10), sulfur dioxide (SO2), and nitrogen dioxides (NO2) were calculated at monitoring stations in 25 study districts. A 2-stage regression approach was used in data analyses. RESULTS: The prevalence of respiratory symptoms was higher among children living near a busy road, those living near chimneys or a factory, those having a coal-burning device, those living with smokers, and those living in a home that had been recently renovated. Among girls, PM10 was associated with persistent cough (odds ratio [OR]PM10 = 1.44; 95% CI, 1.18-1.77), persistent phlegm (ORPM10 = 1.36; 95% CI, 1.02-1.81), and wheezing (ORPM10 = 1.31; 95% CI, 1.04-1.65). NO2 concentration was associated with increased prevalence of allergic rhinitis (OR = 1.96; 95% CI, 1.27-3.02) among girls. In contrast, associations of respiratory symptoms with concentrations of PM10, SO2, and NO2 were not statistically significant among boys. CONCLUSIONS: Air pollution is particularly important in the development of respiratory morbidity among children. Girls may be more susceptible than boys to air pollution.

Predictive equations using regression analysis of pulmonary function for healthy children in Northeast China.

BACKGROUND: There have been few published studies on spirometric reference values for healthy children in China. We hypothesize that there would have been changes in lung function that would not have been precisely predicted by the existing spirometric reference equations. The objective of the study was to develop more accurate predictive equations for spirometric reference values for children aged 9 to 15 years in Northeast China. METHODOLOGY/PRINCIPAL FINDINGS: Spirometric measurements were obtained from 3,922 children, including 1,974 boys and 1,948 girls, who were randomly selected from five cities of Liaoning province, Northeast China, using the ATS (American Thoracic Society) and ERS (European Respiratory Society) standards. The data was then randomly split into a training subset containing 2078 cases and a validation subset containing 1844 cases. Predictive equations used multiple linear regression techniques with three predictor variables: height, age and weight. Model goodness of fit was examined using the coefficient of determination or the R(2) and adjusted R(2). The predicted values were compared with those obtained from the existing spirometric reference equations. The results showed the prediction equations using linear regression analysis performed well for most spirometric parameters. Paired t-tests were used to compare the predicted values obtained from the developed and existing spirometric reference equations based on the validation subset. The t-test for males was not statistically significant (p>0.01). The predictive accuracy of the developed equations was higher than the existing equations and the predictive ability of the model was also validated. CONCLUSION/SIGNIFICANCE: We developed prediction equations using linear regression analysis of spirometric parameters for children aged 9-15 years in Northeast China. These equations represent the first attempt at predicting lung function for Chinese children following the ATS/ERS Task Force 2005 guidelines on spirometry standardization.

[Effects of indoor air pollution on asthma and asthma-related symptoms among children in Shenyang city].

OBJECTIVE: To study the effects of indoor air pollution and individual susceptible factors on prevalence of children's asthma and asthma-related symptoms in Shenyang city. METHODS: On April, 2007, 8733 Han children who were under age of 12 and lived for more than 2 years in Shenyang city, were selected from five administrative areas (one primary school and two kindergartens for each area) through cluster random sampling method. Information on children's general condition, asthma and related symptoms (including stridor, stridor symptoms, persistent cough, persistent phlegm), indoor air pollution, and susceptibility history were obtained by a standard questionnaire from the American Thoracic Society. The effects of indoor air pollution on asthma and asthma-related symptoms was analyzed through χ(2) test. Logistic regression was used to research the effects of risk factors on the prevalence of asthma and asthma-related symptoms of both susceptible and non-susceptible children. RESULTS: Among the 8733 subjects, 4420 (50.6%) were boy and 4313 (49.4%) were girl, with the age of (8.08 ± 2.88) years old. The prevalence of asthma, current asthma, cough, persistent phlegm, stridor and stridor symptom were 6.4% (559 cases), 2.5% (215 cases), 9.6% (836 cases), 4.4% (386 cases), 17.5% (1524 cases) and 2.6% (229 cases) respectively. The prevalence of asthma the boys and girls were among 7.1% (313 cases) and 5.7% (246 cases) (χ(2) = 6.916, P < 0.05); and stridor symptom for them were 19.2% (850 cases), 15.6% (674 cases) (χ(2) = 19.678, P < 0.05), respectively. Passive smoking before two years old, house decoration and pet were related to asthma of children, and there was significant difference between the two groups. The prevalence of asthma of exposed children were 7.7% (312 cases), 9.5% (159 cases), 8.0% (270 cases), 9.0% (114 cases), respectively. Compared with the non-exposed children who had asthma, the prevalence of asthma were 5.7% (400 cases), 5.4% (289 cases), 6.0% (445 cases), the value of χ(2) were 33.646, 23.944 and 16.527 respectively (all P values < 0.05). Children who had family history of asthma, family history of allergy and allergy history were also related with asthma, the prevalence of asthma were 17.3% (106 cases), 13.1% (85 cases), 22.0% (147 cases), compared with the non-exposed children who had asthma, the prevalence of asthma were 5.5% (453), 5.9% (474), 5.1% (412), and there was significant difference between the two groups, the value of χ(2) were 130.522, 59.929 and 293.997, respectively (all P values < 0.05). Logistic regression analysis showed that passive smoking (OR = 1.7, 95%CI: 1.2 - 2.4), house decoration (OR = 1.5, 95%CI: 1.1 - 1.9) and pet (OR = 1.6, 95%CI: 1.1 - 2.3) were statistically significant to asthma in non-susceptible children. While passive smoking (OR = 1.3, 95%CI: 1.0 - 1.7) and house decoration (OR = 1.4, 95%CI: 1.1 - 1.7) were increased the risk of asthma. CONCLUSION: Indoor air pollution is a risk factor of children' s asthma. Family history of asthma and physical susceptible children are high risk to asthma, and susceptible children are easily influenced by other risk factors.

Subchronic effects of perfluorooctanesulfonate exposure on inflammation in adult male C57BL/6 mice.

Previous studies indicate that exposure to perfluorooctanesulfonate (PFOS), a ubiquitous and highly persistent environmental contaminant, induces immunotoxicity in mice. However, few studies have specifically assessed the effects of PFOS on inflammation. This study utilized a standard 60-day oral exposure period to assess the effects of PFOS on the response of inflammatory cytokines [tumor necrosis factor α (TNF-α), interleukin-1 ß (IL-1ß), and interleukin-6 (IL-6)]. Adult male C57BL/6 mice were dosed daily by oral gavage with PFOS at 0, 0.0083, 0.0167, 0.0833, 0.4167, 0.8333 or 2.0833 mg/kg/day to yield a targeted Total Administered Dose (TAD) over 60 days of 0, 0.5, 1, 5, 25, 50, or 125 mg PFOS/kg, respectively. The percentage of peritoneal macrophages (CD11b+ cells) was significantly increased at concentrations ≥ 1 mg PFOS/kg TAD in a dose-dependent manner. Ex vivo IL-1ß production by peritoneal macrophages was elevated substantially at concentrations of ≥ 5 mg PFOS/kg TAD. Moreover, PFOS exposure markedly enhanced the ex vivo production of TNF-α, IL-1ß and IL-6 by peritoneal and splenic macrophages when stimulated either in vitro or in vivo with lipopolysaccharide (LPS). The serum levels of these inflammatory cytokines observed in response to in vivo stimulation with LPS were elevated substantially by exposure to PFOS. PFOS exposure elevated the expression of pro-inflammatory cytokines TNF-α, IL-1ß, IL-6, and proto-oncogene, c-myc, in the spleen. These data suggest that exposure to PFOS modulates the inflammatory response, and further research is needed to determine the mechanism of action.

Prevalence of overweight and obesity among preschool children from six cities of northeast China.

BACKGROUND AND AIMS: This study was carried out to assess and investigate the prevalence of overweight and obesity among preschool-age children living in northeast China using the World Health Organization (WHO), International Obesity Task Force (IOTF) and Centers for Disease Control and Prevention (CDC) standard criteria and to explore the differences in estimates by using the three reference standards. METHODS: We used data from 8,653 preschool children with an average age of 5.02 years. Weight and height were obtained for each child and body mass index (BMI) was calculated. The prevalence of overweight and obesity was then determined using the CDC, IOTF and WHO guidelines. RESULTS: According to the IOTF reference, 10.98% of the children were overweight and 6.08% were obese. The CDC reference classified 11.27% as overweight and 11.72% as obese. However, with the WHO reference, 10.93% were overweight and 13.81% were obese. There was significant gender difference in the prevalence of overweight and obesity based on the CDC and WHO references. According to age classification, differences in the frequencies of obesity in both boys and girls reached statistical significance using the three references, and the differences were gradually improved from the WHO to CDC and IOTF cut-off points. In this study, the WHO and the CDC references demonstrated a high level of agreement (kappa = 0.89). CONCLUSIONS: The results indicate overweight and obesity prevalence among preschool children in northeast China is comparable to some Western countries. The WHO reported a much higher prevalence of obesity compared to other references. Age, gender and method differences in the prevalence of overweight and obesity suggested a systematic evaluation of the preschool children in China.

Fas/FasL pathway-mediated alveolar macrophage apoptosis involved in human silicosis.

In vitro and in vivo studies have demonstrated that lung cell apoptosis is associated with lung fibrosis; however the relationship between apoptosis of alveolar macrophages (AMs) and human silicosis has not been addressed. In the present study, AM apoptosis was determined in whole-lung lavage fluid from 48 male silicosis patients, 13 male observers, and 13 male healthy volunteers. The relationships between apoptosis index (AI) and silica exposure history, soluble Fas (sFas)/membrane-bound Fas (mFas), and caspase-3/caspase-8 were analyzed. AI, mFas, and caspase-3 were significantly higher in lung lavage fluids from silicosis patients than those of observers or healthy volunteers, but the level of sFas demonstrated a decreasing trend. AI was related to silica exposure, upregulation of mFas, and activation of caspase-3 and -8, as well as influenced by smoking status after adjusting for confounding factors. These results indicate that AM apoptosis could be used as a potential biomarker for human silicosis, and the Fas/FasL pathway may regulate this process. The present data from human lung lavage samples may help to understand the mechanism of silicosis and in turn lead to strategies for preventing or treating this disease.

Gender differences and effect of air pollution on asthma in children with and without allergic predisposition: northeast Chinese children health study.

BACKGROUND: Males and females exhibit different health responses to air pollution, but little is known about how exposure to air pollution affects juvenile respiratory health after analysis stratified by allergic predisposition. The aim of the present study was to assess the relationship between air pollutants and asthmatic symptoms in Chinese children selected from multiple sites in a heavily industrialized province of China, and investigate whether allergic predisposition modifies this relationship. METHODOLOGY/PRINCIPAL FINDINGS: 30139 Chinese children aged 3-to-12 years were selected from 25 districts of seven cities in northeast China in 2009. Information on respiratory health was obtained using a standard questionnaire from the American Thoracic Society. Routine air-pollution monitoring data was used for particles with an aerodynamic diameter ≤10 µm (PM(10)), sulfur dioxide (SO(2)), nitrogen dioxides (NO(2)), ozone (O(3)) and carbon monoxide (CO). A two-stage regression approach was applied in data analyses. The effect estimates were presented as odds ratios (ORs) per interquartile changes for PM(10), SO(2), NO(2), O(3), and CO. The results showed that children with allergic predisposition were more susceptible to air pollutants than children without allergic predisposition. Amongst children without an allergic predisposition, air pollution effects on asthma were stronger in males compared to females; Current asthma prevalence was related to PM(10) (ORs = 1.36 per 31 µg/m(3); 95% CI, 1.08-1.72), SO(2) (ORs = 1.38 per 21 µg/m(3); 95%CI, 1.12-1.69) only among males. However, among children with allergic predisposition, more positively associations between air pollutants and respiratory symptoms and diseases were detected in females; An increased prevalence of doctor-diagnosed asthma was significantly associated with SO(2) (ORs = 1.48 per 21 µg/m(3); 95%CI, 1.21-1.80), NO(2) (ORs = 1.26 per 10 µg/m(3); 95%CI, 1.01-1.56), and current asthma with O(3) (ORs = 1.55 per 23 µg/m(3); 95%CI, 1.18-2.04) only among females. CONCLUSION/SIGNIFICANCE: Ambient air pollutions were more evident in males without an allergic predisposition and more associations were detected in females with allergic predisposition.

Gender-specific differences in effects of prenatal and postnatal environmental tobacco smoke exposure on respiratory symptoms in 23,474 children with and without allergic predisposition: results from 25 districts of northeast China.

To assess the interaction of environmental tobacco smoke (ETS) exposure and allergic predisposition regarding respiratory health among Chinese children, a sample of 23,474 children (6-13 years old) was studied from 25 districts in Liaoning province, China. The results showed that children without allergic predisposition were more susceptible to ETS than children with allergic predisposition. Among children without allergic predisposition, ETS exposure was associated with more respiratory symptoms and diseases in boys than in girls; In utero ETS exposure was associated with history of asthma (OR, 1.86; 95% CI, 1.44-2.40) and current asthma (OR, 2.25; 95% CI, 1.48-3.44) only among boys without allergic predisposition. Among children with allergic predisposition, more associations between ETS exposure and respiratory symptoms and diseases were detected in girls. In conclusion, ETS exposure was more evident in boys without family atopy history and more associations were detected in girls with family atopy history.

Type 1 and Type 2 cytokines imbalance in adult male C57BL/6 mice following a 7-day oral exposure to perfluorooctanesulfonate (PFOS).

Previous studies indicate that exposure to perfluorooctanesulfonate (PFOS), a ubiquitous and highly persistent environmental contaminant induces immunotoxicity in mice. However, clear mechanisms to explain any PFOS-induced immunotoxicity are still unknown. The study here sought to examine the ability of PFOS to potentially perturb T-helper (T(H))-1 and -2 cell cytokine secreting activities, as well as to cause shifts in antibody isotype levels, as possible mechanisms involved in PFOS-induced immunotoxicity. Adult male C57BL/6 mice were given by gavage 0, 5, or 20 mg PFOS/kg/d for 7 days. One day after the final exposure, spleens from these hosts were isolated and used for analyses of the ex vivo production of T(H)1-type (interleukin-2 (IL-2), interferon-γ (IFNγ), T(H)2-type (IL-4), and IL-10 cytokines by isolated splenocytes. In addition, serum was isolated from these mice in order to assess their levels of immunoglobulin M (IgM) and IgG antibodies. In all studies, levels of the cytokines of the antibodies were quantified via enzyme-linked immunosorbent assay or enzyme-linked immunosorbent spot. The results here showed that IL-2 and IFNγ formation was reduced, but that IL-4 production increased by the 5 and 20 mg PFOS/kg/d treatments. Serum IgM levels decreased significantly (in dose-related manner) as a result of the PFOS exposures; serum IgG levels increased markedly with 5 mg PFOS/kg/d, but decreased slightly with the 20 mg PFOS/kg/d regimens PFOS exposure increased serum corticosterone levels in a dose-dependent manner. These results indicated that, after a high-dose short-term exposure to PFOS, a host's immune state is likely to be characterized by a shift toward a more T(H)2-like state that, in turn, may lead to suppression of their cellular response and enhancement of their humoral response.

Health economic assessment for screening of gastric cancer in a high risk population in northeastern china.

OBJECTIVE: To assess economic cost-effects for the screening programs of gastric cancer in a high risk population in northeastern China. METHODS: The data were collected from November 2001 to December 2003. The multi-stage sampling to define the screening group and the control group was applied in this study. Two stage screening programs were used in the study. An epidemiological survey and serum PG test were carried out in the first stage. The endoscopy and pathological examination were performed in the second stage screening. Effectiveness was assessed by the increased quality adjusted life-year (QALY) because of reduced gastric cancer deaths in screening. RESULTS: A total of 27,970 participants (n=7,128 screening group, n=20,842 control group) were enrolled in the survey. Twenty nine gastric cancer cases were detected in the screening group with 20 cases in the early stage and 9 cases in the advanced stage, respectively. Eighty six gastric cancer cases were detected in the control group, all of whom were in the advanced stage and had died before the study finished. The screening and treatment of 29 cases cost $152,227 and $5,249 per each case, respectively. The costs were $459 to gain per QALY. CONCLUSION: The screening program of gastric cancer used in our study is an economic and society-beneficial measure to detect gastric cancer in high risk area. The methods fit China's present economic development level.

Exposure to secondhand tobacco smoke enhances respiratory symptoms and responses to animals in 8,819 children in kindergarten: results from 25 districts in northeast China.

BACKGROUND: Experimental data suggest that asthma exacerbation by allergens is enhanced by exposure to environmental tobacco smoke (ETS); however, there is little supporting epidemiologic evidence. To our knowledge, few studies have assessed respiratory symptoms and allergies in this context. OBJECTIVES: To evaluate whether the association of exposure to animals (indicators of allergen and endotoxin exposure) with asthma-related symptoms is modified by ETS exposure in Chinese children. METHODS: A cross-sectional study of 8,819 children in kindergarten was conducted in 25 districts in northern China. Information on respiratory health and exposure to indoor allergens was obtained using a standard questionnaire from the American Thoracic Society. RESULTS: Among the children with ETS exposure in utero, the effects of exposure to animals were significant with respect to persistent cough [adjusted odds ratio (OR) 1.83; 95% confidence interval (CI) 1.12-2.99] and persistent phlegm (adjusted OR 2.40; 95% CI 1.28-4.54). The combined effect of in utero ETS exposure and animal exposure on doctor-diagnosed asthma was approximately as expected on the basis of their independent effects on an additive scale. There was no interaction between animal exposure and ETS exposure in the first 2 years of life or current ETS exposure. CONCLUSIONS: This study provides evidence that animal and ETS exposure increases the risk of asthma-related symptoms in children in kindergarten. ETS exposure in utero did modify the effect of animal exposure on persistent phlegm and persistent cough but not on doctor-diagnosed asthma among children.

CD4+CD25+Foxp3+ regulatory T cells depletion may attenuate the development of silica-induced lung fibrosis in mice.

BACKGROUND: Silicosis is an occupational lung disease caused by inhalation of silica dust characterized by lung inflammation and fibrosis. Previous study showed that Th1 and Th2 cytokines are involved in silicosis, but Th1/Th2 polarization during the development of silicosis is still a matter of debate. Regulatory T cells (Treg cells) represent a crucial role in modulation of immune homeostasis by regulating Th1/Th2 polarization, but their possible implication in silicosis remains to be explored. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate the implication of Treg cells in the development of silicosis, we generated the Treg-depleted mice model by administration of anti-CD25 mAbs and mice were exposed to silica by intratracheal instillation to establish experimental model of silica-induced lung fibrosis. The pathologic examinations show that the Treg-depleted mice are susceptive to severer inflammation in the early stage, with enhanced infiltration of inflammatory cells. Also, depletion of Treg cells causes a delay of the progress of silica-induced lung fibrosis in mice model. Further study of mRNA expression of cytokines reveals that depletion of Tregs leads to the increased production of Th1-cytokines and decreased production of Th2-cytokine. The Flow Cytometry and realtime PCR study show that Treg cells exert the modulation function both directly by expressing CTLA-4 at the inflammatory stage, and indirectly by secreting increasing amount of IL-10 and TGF-ß during the fibrotic stage in silica-induced lung fibrosis. CONCLUSION/SIGNIFICANCE: Our study suggests that depletion of Tregs may attenuate the progress of silica-induced lung fibrosis and enhance Th1 response and decelerate Th1/Th2 balance toward a Th2 phenotype in silica-induced lung fibrosis. The regulatory function of Treg cells may depend on direct mechanism and indirect mechanism during the inflammatory stage of silicosis.

ERCC2, ERCC1 polymorphisms and haplotypes, cooking oil fume and lung adenocarcinoma risk in Chinese non-smoking females.

BACKGROUND: Excision repair cross-complementing group 1 (ERCC1) and group 2 (ERCC2) proteins play important roles in the repair of DNA damage and adducts. Single nucleotide polymorphisms (SNPs) of DNA repair genes are suspected to influence the risk of lung cancer. This study aimed to investigate the association between the ERCC2 751, 312 and ERCC1 118 polymorphisms and the risk of lung adenocarcinoma in Chinese non-smoking females. METHODS: A hospital-based case-control study of 285 patients and 285 matched controls was conducted. Information concerning demographic and risk factors was obtained for each case and control by a trained interviewer. After informed consent was obtained, each person donated 10 ml blood for biomarker testing. Three polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: This study showed that the individuals with the combined ERCC2 751AC/CC genotypes were at an increased risk for lung adenocarcinoma compared with those carrying the AA genotype [adjusted odds ratios (OR) 1.64, 95% confidence interval (CI) 1.06-2.52]. The stratified analysis suggested that increased risk associated with ERCC2 751 variant genotypes (AC/CC) was more pronounced in individuals without exposure to cooking oil fume (OR 1.98, 95%CI 1.18-3.32) and those without exposure to fuel smoke (OR 2.47, 95%CI 1.46-4.18). Haplotype analysis showed that the A-G-T and C-G-C haplotypes were associated with increased risk of lung adenocarcinoma among non-smoking females (ORs were 1.43 and 2.28, 95%CIs were 1.07-1.91 and 1.34-3.89, respectively). CONCLUSION: ERCC2 751 polymorphism may be a genetic risk modifier for lung adenocarcinoma in non-smoking females in China.