Respiratory symptoms following wildfire smoke exposure: airway size as a susceptibility factor.

Background: Associations between exposure to smoke during wildfire events and respiratory symptoms are well documented, but the role of airway size remains unclear. We conducted this analysis to assess whether small airway size modifies these relationships.

Methods: We analyzed data from 465 nonasthmatic 16- to 19-year-old participants in the Children's Health Study.

Ambient ozone modifies the effect of tumor necrosis factor G-308A on bronchitic symptoms among children with asthma.

Background: Tumor necrosis factor (TNF)-alpha has a recognized role in respiratory pathophysiology. One genetic variant (G-308A) in the promoter region affecting the expression of this cytokine may contribute to airway inflammatory diseases, but the studies on bronchitic symptoms were still inconclusive. Because ozone produces oxidative stress, increased airway TNF, and inflammation, the associations of the TNF-308 polymorphism with bronchitic symptoms may vary by ambient ozone exposure.

Variation in the GST mu locus and tobacco smoke exposure as determinants of childhood lung function.

Rationale: The glutathione S-transferases (GSTs) are important detoxification enzymes.

Objectives: To investigate effects of variants in GST mu genes on lung function and assess their interactions with tobacco smoke exposure.

Methods: In this prospective study, 14,836 lung function measurements were collected from 2,108 children who participated in two Southern California cohorts.

Glutathione-S-transferase (GST) P1, GSTM1, exercise, ozone and asthma incidence in school children.

Background: Because asthma has been associated with exercise and ozone exposure, an association likely mediated by oxidative stress, we hypothesised that glutathione-S-transferase (GST)P1, GSTM1, exercise and ozone exposure have interrelated effects on the pathogenesis of asthma.

Methods: Associations of the well characterised null variant of GSTM1 and four single nucleotide polymorphisms (SNPs) that characterised common variation in the GSTP1 locus with new onset asthma in a cohort of 1610 school children were examined. Children's exercise and ozone exposure were classified using participation in team sports and community annual average ozone levels, respectively.

Difference in airflow obstruction between Hispanic and non-Hispanic White female smokers.

Smoking-related respiratory diseases are a major cause of morbidity and mortality. However, the relationship between smoking and respiratory disease has not been well-studied among ethnic minorities in general and among women in particular. The objective of this cross-sectional study was to evaluate the risk of airflow obstruction and to assess lung function among Hispanic and non-Hispanic White (NHW) female smokers in a New Mexico cohort.

Association between alcohol intake and serum sex hormones and peptides differs by tamoxifen use in breast cancer survivors.

Objective: To measure the association between alcohol intake and 11 hormones and peptides in postmenopausal breast cancer survivors and to evaluate whether this association differs by tamoxifen use.

Methods: Self-reported alcohol intake was assessed via food frequency questionnaire on average 30 months post-breast cancer diagnosis in 490 postmenopausal women from three western states. Concurrently, a fasting blood sample was obtained for assay of estrone, estradiol, free estradiol, testosterone, free testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG), leptin, C-peptide, insulin-like growth factor-I (IGF-I), and IGF-binding protein-3.

Traffic-related air pollution and asthma onset in children: a prospective cohort study with individual exposure measurement.

Background: The question of whether air pollution contributes to asthma onset remains unresolved.

Objectives: In this study, we assessed the association between asthma onset in children and traffic-related air pollution.

Methods: We selected a sample of 217 children from participants in the Southern California Children's Health Study, a prospective cohort designed to investigate associations between air pollution and respiratory health in children 10-18 years of age.

Relationships of online exhaled, offline exhaled, and ambient nitric oxide in an epidemiologic survey of schoolchildren.

Unlabelled: Field measurements of exhaled nitric oxide (FeNO) and ambient nitric oxide (NO) are useful to assess both respiratory health and short-term air pollution exposure. Online real-time measurement maximizes data quality and comparability with clinical studies, but offline delayed measurement may be more practical for large epidemiological studies. To facilitate cross-comparison in larger studies, we measured FeNO and concurrent ambient NO both online and offline in 362 children at 14 schools in 8 Southern California communities.

Breast cancer survivors who use estrogenic botanical supplements have lower serum estrogen levels than non users.

To measure the association between use of estrogenic botanical supplements and serum sex hormones in postmenopausal breast cancer survivors, a total 502 postmenopausal women were queried 2-3 years after breast cancer diagnosis about their use of botanical supplements, and supplements were categorized according to their estrogenic properties. Concurrently, a fasting blood sample was obtained for assay of estrone, estradiol, free estradiol, testosterone, free testosterone, dehydroepiandrosterone sulfate (DHEAS), and sex hormone-binding globulin. Adjusted means of the serum hormones were calculated by use of estrogenic supplements.

Influence of pre- and postdiagnosis physical activity on mortality in breast cancer survivors: the health, eating, activity, and lifestyle study.

Purpose: To investigate the association between pre- and postdiagnosis physical activity (as well as change in prediagnosis to postdiagnosis physical activity) and mortality among women with breast cancer.

Patients And Methods: This was a prospective observational study of 933 women enrolled onto the Health, Eating, Activity, and Lifestyle Study who were diagnosed with local or regional breast cancer between 1995 and 1998 and observed until death or September 2004, whichever came first. The primary outcomes measured were total deaths and breast cancer deaths.

Association between common genetic variation in Cockayne syndrome A and B genes and nucleotide excision repair capacity among smokers.

Mutagen sensitivity in in vitro cultured lymphocytes challenged by benzo[a]pyrene diolepoxide (BPDE) has been validated as an intrinsic susceptibility factor for several cancers. Bulky BPDE-DNA adducts are repaired via either transcription-coupled repair or global genome nucleotide excision repair depending on the location of lesions. Cockayne syndrome A (CSA) and B (CSB) play essential roles in integrating the recognition of damage, chromatin remodeling, and the core nucleotide excision repair proteins.

Vitamin D insufficiency in a multiethnic cohort of breast cancer survivors.

Background: Little is known about vitamin D status in breast cancer survivors. This issue is important because vitamin D influences pathways related to carcinogenesis.

Objective: The objective of this report was to describe and understand vitamin D status in a breast cancer survivor cohort.

Effects of in utero and childhood tobacco smoke exposure and beta2-adrenergic receptor genotype on childhood asthma and wheezing.

Objective: Associations between single-nucleotide polymorphisms in the beta2-adrenergic receptor gene and asthma and wheeze have been inconsistent. Recent studies indicated that tobacco smoke affects beta2-adrenergic receptor gene expression and associations of beta2-adrenergic receptor gene variants with asthma in adults. We aimed to investigate the joint effects of in utero and childhood secondhand tobacco smoke exposure and 2 well-characterized functional single-nucleotide polymorphisms (Arg16Gly and Glu27Gln) of beta2-adrenergic receptor gene on asthma and wheezing in 3128 non-Hispanic and Hispanic white children of the Children's Health Study.

Haplotypes of DNMT1 and DNMT3B are associated with mutagen sensitivity induced by benzo[a]pyrene diol epoxide among smokers.

The mutagen sensitivity assay is an in vitro measure of DNA repair capacity used to evaluate intrinsic susceptibility for cancer. The high heritability of mutagen sensitivity to different mutagens validates the use of this phenotype to predict cancer susceptibility. However, genetic determinants of mutagen sensitivity have not been fully characterized.

5-year urinary and sexual outcomes after radical prostatectomy: results from the Prostate Cancer Outcomes Study.

Purpose: Prior studies of postoperative outcomes following radical prostatectomy have been limited by selection bias and short-term followup. In this study we assessed temporal changes in urinary and sexual function up to 5 years following radical prostatectomy in a population based cohort.

Materials And Methods: A sample of 1,288 men with localized prostate cancer who underwent radical prostatectomy and completed a baseline survey within 6 to 12 months of diagnosis were included in the analysis.

Double-strand break damage and associated DNA repair genes predispose smokers to gene methylation.

Gene promoter hypermethylation in sputum is a promising biomarker for predicting lung cancer. Identifying factors that predispose smokers to methylation of multiple gene promoters in the lung could affect strategies for early detection and chemoprevention. This study evaluated the hypothesis that double-strand break (DSB) repair capacity and sequence variation in genes in this pathway are associated with a high methylation index in a cohort of current and former cancer-free smokers.

Correlates of circulating C-reactive protein and serum amyloid A concentrations in breast cancer survivors.

Introduction: Inflammatory status may be an important prognostic factor for breast cancer. Correlates of markers of inflammation in breast cancer survivors have not been thoroughly evaluated.

Methods: Using data from, the Health, Eating, Activity, and Lifestyle (HEAL) Study (a population-based, multiethnic prospective cohort study of female breast cancer patients) we evaluated the associations between circulating markers of inflammation (C-reactive protein [CRP] and serum amyloid A [SAA], measured approximately 31 months after diagnosis) and several demographic, lifestyle, and clinical characteristics in 741 disease-free breast cancer survivors.

Glutathione S-transferase P1, maternal smoking, and asthma in children: a haplotype-based analysis.

Background: Glutathione S-transferase P1 (GSTP1) plays a role in a spectrum of respiratory diseases; however, the effects of sequence variation across the entire locus in asthma pathogenesis have yet to be determined.

Objectives: This study was designed to investigate whether sequence variations in the GSTP1 coding and promoter regions are associated with asthma and wheezing outcomes and to determine whether variants affect susceptibility to maternal smoking.

Methods: Four haplotype tagging SNPs were selected that accounted for 83% of the common haplotypic variation in GSTP1.

Associations of FcepsilonRIbeta E237G polymorphism with wheezing in Taiwanese schoolchildren.

Background: The beta-chain of a high-affinity IgE receptor (FcepsilonRIbeta) has been proposed as a candidate gene for atopic diseases, but previous studies have come to inconsistent conclusions. Because some air pollutants would produce oxidative stress, increase serum IgE, and trigger T-helper type 2 (Th2)-type airway inflammation, the associations of FcepsilonRIbeta polymorphism with wheezing illness may vary by their exposures and variants of oxidant defence genes. The purpose of this study was to investigate the association of FcepsilonRIbeta E237G polymorphism with wheezing illness and to determine whether these associations vary with air pollution and glutathione S-transferase (GST) P1-105 and M1 genotypes.

Ozone, oxidant defense genes, and risk of asthma during adolescence.

Rationale: Although oxidative stress is a cardinal feature of asthma, the roles of oxidant air pollutants and antioxidant genes heme oxygenase 1 (HMOX-1), catalase (CAT), and manganese superoxide dismutase (MNSOD) in asthma pathogenesis have yet to be determined.

Objectives: We hypothesized that the functional polymorphisms of HMOX-1 ([GT](n) repeat), CAT (-262C>T -844C>T), and MNSOD (Ala-9Val) are associated with new-onset asthma, and the effects of these variants vary by exposure to ozone, a potent oxidant air pollutant.

Methods: We assessed this hypothesis in a population-based cohort of non-Hispanic (n = 1,125) and Hispanic white (n = 586) children who resided in 12 California communities and who were followed annually for 8 years to ascertain new-onset asthma.

Genotypes in matrix metalloproteinase 9 are a risk factor for COPD.

A growing body of evidence indicates that matrix metalloproteinases (MMPs) play a role in the pathogenesis of COPD. Therefore, we conducted a candidate gene association study of 4 promoter polymorphisms that are known to modify expression levels of the MMP-1, MMP-2, and MMP-9 genes and a Gln279Arg polymorphism in exon 6 of MMP-9 that modifies the substrate-binding region. We examined the association of each variant and haplotypes in 385 male veterans with greater than 20 pack-years of cigarette smoking whose COPD status was characterized using spirometry.

Recent evidence for adverse effects of residential proximity to traffic sources on asthma.

Purpose Of Review: A growing body of evidence indicates that residential proximity to traffic sources increases the risk for asthma and asthma exacerbations. In this review we have considered publications from 2006-2007 that examined the impact of residential traffic-related exposures on asthma occurrence and severity.

Recent Findings: In these studies, exposures were estimated using traffic metrics based on residential distances from major roads and freeways, traffic densities around homes, and models of traffic exposure.

Radiation-induced lung adenocarcinoma is associated with increased frequency of genes inactivated by promoter hypermethylation.

Epigenetic inactivation of genes by promoter hypermethylation, a major mechanism in the initiation and progression of tobacco-induced cancer, has also been associated with lung cancer induced through environmental and occupational exposures. Our previous study of gene methylation in workers from the MAYAK nuclear enterprise identified a significantly higher prevalence for methylation of the p16 gene (CDKN2A) in adenocarcinomas from workers compared to tumors from non-worker controls. The purpose of this investigation was to determine whether genes in addition to p16 are "targeted" for silencing and whether overall gene methylation was more common in radiation-induced adenocarcinoma.

Microsomal epoxide hydrolase, glutathione S-transferase P1, traffic and childhood asthma.

Background: Microsomal epoxide hydrolase (EPHX1) metabolises xenobiotics including polyaromatic hydrocarbons (PAHs). Functional variants at this locus have been associated with respiratory diseases. The effects of EPHX1 variants may depend upon exposures from tobacco smoke and traffic emissions that contain PAHs as well as variants in other enzymes in the PAH metabolic pathway such as glutathione S-transferase (GST) genes.

Transforming growth factor- 1 C-509T polymorphism, oxidant stress, and early-onset childhood asthma.

Rationale: Transforming growth factor (TGF)-beta1 is involved in airway inflammation and remodeling, two key processes in asthma pathogenesis. Tobacco smoke and traffic emissions induce airway inflammation and modulate TGF-beta1 gene expression. We hypothesized that the effects of functional TGF-beta1 variants on asthma occurrence vary by these exposures.