Michelle K. McHugh

Prevalence of Asthma among Adult Females and Males in the United States: Results from the National Health and Nutrition Examination Survey (NHANES), 2001–2004

BACKGROUND The prevalence of asthma has increased over the last three decades with females exhibiting a higher prevalence of asthma than males. The objective of this study was to obtain gender-specific estimates of the prevalence of current and ever asthma and describe the relationships between risk factors and asthma by gender in US men and women ages 20 to 85. METHODS Data for this study came from two cycles (2001-2002 and 2003-2004) of National Health and Nutrition Examination Survey (NHANES) and included 9,243 eligible adults: 4,589 females and 4,654 males. Multiple logistic regression was used to investigate gender-specific associations between race/ethnicity, body mass index (BMI), sociodemographic characteristics, and smoking habits for current asthma and ever asthma. RESULTS The prevalence of current asthma was 8.8% for women and 5.8% for men, while the prevalence of ever having been diagnosed with asthma was higher (13.7% and 10.4% for women and men, respectively). Current asthma was less prevalent in Mexican American women (1.9%) and men (0.9%) born in Mexico as compared to Mexican Americans born in the U.S. (8.7% and 5.2% for women and men, respectively) or for any other ethnic group. Approximately 20% of extremely obese women and men had ever been diagnosed with asthma; among this group, 15% reported they had current asthma. Results from multiple logistic regression models indicate that extreme obesity and living in poverty were strongly associated with current and ever asthma for both women and men, as was former smoking and ever asthma for men. CONCLUSION As compared to previous NHANES reports, our results indicate that the prevalence of asthma among U.S. adults continues to increase. Further, our findings of marked differences among subgroups of the population suggest asthma-related disparities for impoverished persons and greater prevalence of asthma among obese and extremely obese US adults.

Genome-wide gene–environment interaction analysis for asbestos exposure in lung cancer susceptibility

Abstract Asbestos exposure is a known risk factor for lung cancer. Although recent genome-wide association studies (GWASs) have identified some novel loci for lung cancer risk, few addressed genome-wide gene–environment interactions. To determine gene–asbestos interactions in lung cancer risk, we conducted genome-wide gene–environment interaction analyses at levels of single nucleotide polymorphisms (SNPs), genes and pathways, using our published Texas lung cancer GWAS dataset. This dataset included 317 498 SNPs from 1154 lung cancer cases and 1137 cancer-free controls. The initial SNP-level P -values for interactions between genetic variants and self-reported asbestos exposure were estimated by unconditional logistic regression models with adjustment for age, sex, smoking status and pack-years. The P- value for the most significant SNP rs13383928 was 2.17×10 –6 , which did not reach the genome-wide statistical significance. Using a versatile gene-based test approach, we found that the top significant gene was C7orf54 , located on 7q32.1 ( P = 8.90×10 –5 ). Interestingly, most of the other significant genes were located on 11q13. When we used an improved gene-set-enrichment analysis approach, we found that the Fas signaling pathway and the antigen processing and presentation pathway were most significant (nominal P < 0.001; false discovery rate < 0.05) among 250 pathways containing 17 572 genes. We believe that our analysis is a pilot study that first describes the gene–asbestos interaction in lung cancer risk at levels of SNPs, genes and pathways. Our findings suggest that immune function regulation-related pathways may be mechanistically involved in asbestos-associated lung cancer risk. Abbreviations:CI confidence intervalE environmentFDR false discovery rateG geneGSEA gene-set-enrichment analysisGWAS genome-wide association studiesi-GSEA improved gene-set-enrichment analysis approachOR odds ratioSNP single nucleotide polymorphism

Use of the Cytokinesis-Blocked Micronucleus Assay to Detect Gender Differences and Genetic Instability in a Lung Cancer Case–Control Study

Background: Although tobacco exposure is the predominant risk factor for lung cancer, other environmental agents are established lung carcinogens. Measuring the genotoxic effect of environmental exposures remains equivocal, as increases in morbidity and mortality may be attributed to coexposures such as smoking. Methods: We evaluated genetic instability and risk of lung cancer associated with exposure to environmental agents (e.g., exhaust) and smoking among 500 lung cancer cases and 500 controls using the cytokinesis-blocked micronucleus (CBMN) assay. Linear regression was applied to estimate the adjusted means of the CBMN endpoints (micronuclei and nucleoplasmic bridges). Logistic regression analyses were used to estimate lung cancer risk and to control for potential confounding by age, gender, and smoking. Results: Cases showed significantly higher levels of micronuclei and nucleoplasmic bridges as compared with controls (mean ± SEM = 3.54 ± 0.04 vs. 1.81 ± 0.04 and mean ± SEM = 4.26 ± 0.03 vs. 0.99 ± 0.03, respectively; P < 0.001) with no differences among participants with or without reported environmental exposure. No differences were observed when stratified by smoking or environmental exposure among cases or controls. A difference in lung cancer risk was observed between nonexposed male and female heavy smokers, although it was not statistically significant (I2 = 64.9%; P value for Q statistic = 0.09). Conclusions: Our study confirms that the CBMN assay is an accurate predictor of lung cancer and supports the premise that heavy smoking may have an effect on DNA repair capacity and in turn modulate the risk of lung cancer. Impact: Identifying factors that increase lung cancer risk may lead to more effective prevention measures. Cancer Epidemiol Biomarkers Prev; 22(1); 135–45. ©2012 AACR.

The feasibility of adapting a population-based asthma-specific job exposure matrix (JEM) to NHANES

BACKGROUND To determine the feasibility of applying a job exposure matrix (JEM) for classifying exposures to 18 asthmagens in the National Health and Nutrition Examination Survey (NHANES), 1999-2004. METHODS We cross-referenced 490 National Center for Health Statistics job codes used to develop the 40 NHANES occupation groups with 506 JEM job titles and assessed homogeneity in asthmagen exposure across job codes within each occupation group. RESULTS In total, 399 job codes corresponded to one JEM job title, 32 to more than one job title, and 59 were not in the JEM. Three occupation groups had the same asthmagen exposure across job codes, 11 had no asthmagen exposure, and 26 groups had heterogeneous exposures across jobs codes. CONCLUSION The NHANES classification of occupations limits the use of the JEM to evaluate the association between workplace exposures and asthma and more refined occupational data are needed to enhance work-related injury/illness surveillance efforts.

Evaluating narrow windows of maternal exposure to ozone and preterm birth in a large urban area in Southeast Texas

The association between O3 exposure and preterm birth (PTB) remains unclear. We evaluated associations for three categories of PTB and O3 in Harris County, Texas, during narrow periods of gestation. We computed two sets of exposure metrics during every 4 weeks of pregnancy for 152,214 mothers who delivered singleton, live-born infants in 2005–2007, accounting first for temporal variability and then for temporal and spatial sources of variability in ambient O3 levels. Associations were assessed using multiple logistic regression. We also examined the potential for a fixed cohort bias. In the bias-corrected cohort where associations were somewhat stronger, elevated odds ratios (ORs) per 10 parts per billion increase in O3 exposure (county-level metric) were detected for the fifth (OR=1.08, 95% confidence interval (CI): 1.04–1.12), sixth (OR=1.05, 95% CI=1.01–1.09), and seventh (OR=1.07, 95% CI=1.03–1.10) 4-week periods of pregnancy for late PTB (33–36 completed weeks gestation), the fifth (OR=1.13, 95% CI=1.02–1.25) and seventh (OR=1.15, 95% CI=1.04–1.27) 4-week periods of pregnancy for moderate PTB (29–32 completed weeks gestation), and the fifth (OR=1.21, 95% CI=1.08–1.36) 4-week period of pregnancy for severe PTB (20–28 completed weeks gestation). Conversely, decreased odds were found in the first 4-week period of pregnancy for severe PTB (OR=0.83, 95% CI=0.74–0.94). Associations were slightly attenuated using the spatially interpolated (kriged) metrics, and for women who did not work outside of the home. Our analyses confirm reports in other parts of the United States and elsewhere with findings that suggest that maternal exposure to ambient levels of O3 is associated with PTB.

Abstract 1878: Evidence for the indirect relationship between self-reported exposure to environmental agents and smoking in the assessment of lung cancer risk

Genetic factors play a role in determining individual susceptibility to cancer. Accumulation of multiple genetic alterations leads to cancer development and is cytogenetically detectable. Our group has applied the Cytonkinesis-Blocked Micronucleus assay (CBMN) as a sensitive predictor of individual susceptibility to lung cancer (LC). The objective of this study was to investigate whether self-reported exposure to ≥1 environmental agents (asbestos, fibers, paints, dust, exhaust, bleach, solvents) is associated with increased genetic instability and/or elevated risk of LC. We recruited 490 LC cases from an ongoing study at the University of Texas MD Anderson Cancer Center. Controls (n=500) were recruited from a large multispecialty physician group practice and frequency matched to cases by age (±5 years) and sex. Peripheral blood lymphocytes were collected and cytogenetic cultures prepared. One thousand binucleated cells per participant were scored and the frequencies of micronucleus (BN-MN), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) were recorded. Linear regression analyses were applied to estimate the adjusted means of the CBMN. Odds ratios and 95% confidence intervals were calculated using logistic regression and to control for confounding. We did not detect elevated odds of LC when exposure was assessed by self-report to ≥1 of the seven environmental agents. When stratified by smoking status, we found heavy smokers with ≥1 exposure had a 58% increased risk of LC compared to never smokers without exposure; yet heavy smokers with no exposure had a 79% increased risk compared to the referent group. Even though LC cases showed significantly higher frequencies than controls for all three CBMN endpoints, there were no significant differences in cases with or without exposure (p=0.15). However in controls, the differences were indirectly related to exposure. Mean BN-MN for controls without exposure (mean +SE = 2.68±0.07) was higher than the mean BN-MN for controls with ≥1 exposure (mean +SE = 2.44±0.07). We also found an indirect relationship between mean BN-MN levels and smoking among controls: never smokers (mean +SE = 2.81±0.09), light (mean +SE=2.76±0.11, moderate (mean +SE=2.51±0.11) and heavy smokers (mean +SE=2.26±0.10; p for trend= These results confirm our previous studies that found the CBMN assay to be a valuable tool for predicting LC risk; however, the risk confirmed by this biomarker is not related to exposure to the seven agents under study. Our new findings that CBMN frequencies were higher in the controls that were never or light smokers support the hypothesis that heavy smokers may develop a more robust DNA repair machinery due to the constant exposure to smoking-related carcinogens. These findings warrant the need for further studies to identify the underlying mechanisms involved in genetic susceptibility to lung cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1878. doi:10.1158/1538-7445.AM2011-1878

Abstract B91: Self-reported prior lung disease as risk factors for non-small cell lung cancer in Mexican Americans

Background: Although cigarette smoking is the primary risk factor for lung cancer, other risk factors have been shown to be associated with lung cancer including prior history of respiratory diseases. The purpose of this analysis was to assess the association between prior history of respiratory disease (i.e., asthma, chronic obstructive pulmonary disease (COPD), hay fever, and pneumonia) and lung cancer among Mexican Americans using data from a multi-racial/ethnic lung cancer case-control study. Methods: The data were collected between 1991 and 2010. Cases (n = 217) were patients who presented with newly diagnosed, histopathologically confirmed and previously untreated lung cancer. Healthy control participants (n = 339) were recruited from a large multispecialty physician group practice. Demographics, cigarette use, and history of respiratory disease were collected by personal interview using a validated questionnaire. Multivariable logistic regression models were used to estimate relative risk. All analyses were restricted to self-report Mexican Americans. Results: Prior history of COPD (OR = 2.33; 95% CI = 1.14–4.79) and pneumonia (OR = 2.88; 95% CI = 1.47–5.63) were associated with a statistically significant increased risk of lung cancer. Conversely, self-reported history of asthma (OR = 0.71, 95% CI = 0.20–2.45) or hay fever (OR = 0.59, 95% CI = 0.29–1.21) were inversely associated with lung cancer risk but the odds ratios were not statistically significant. Conclusions: These findings illustrate that COPD and pneumonia are associated with an increased for lung cancer among Mexican Americans. Identifying risk factors such as C. pneumonia infections and COPD may induce targeted treatments to help attenuate progression to lung cancer. At present this study is one of largest case-control analyses assessing respiratory disease and lung cancer risk among Mexican-Americans. Citation Information: Cancer Prev Res 2011;4(10 Suppl):B91.

Abstract LB-400: Conventional and anti-microbial pesticide exposures and increased risk of lung cancer in Mexican Americans

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Objective: We investigated demographic factors, environmental and occupational exposures, and medical and family cancer histories in a population of Mexican-American lung cancer cases and controls from the Houston Metropolitan area. Methods: Data were collected as a part of a multi-racial/ethnic on-going lung cancer case-control study. Cases included 212 Mexican American lung cancer cases. Controls (n=328) were recruited from Houstons largest multispecialty group practice and frequency matched to the cases by age (±5 years), sex and ethnicity. Odds ratios and 95% confidence intervals were calculated using logistic regression analysis. Environmental and occupational factors were analyzed individually; however pesticides were analyzed as: 1) any exposure to conventional or antimicrobial pesticides; 2) exposure to conventional pesticides only; and 3) exposure to antimicrobial pesticides only. Results: We detected elevated risks of lung cancer associated with asbestos, wood dust, fibers, SVF, benzene, toluene/xylene, dry cleaning fluids, vehicle exhaust, glues and plastics; however only pesticide exposure was statistically significant. We found both conventional and anti-microbial pesticide exposures were associated with an increased risk of lung cancer in Mexican Americans (conventional pesticides and antimicrobial pesticides combined: OR=1.80, 95%CI 1.13-2.86; conventional pesticides: OR=2.05, 95% CI 1.23-2.39; and anti-microbial pesticides: OR=2.48, 95% CI 1.46-4.21). Conclusions: Although we found over a two-fold increased risk of lung cancer among Mexican Americans for conventional and anti-microbial pesticides, we were not able to identify individual pesticides. Our findings are descriptive in nature and we believe are a necessary and important preliminary step in identifying factors that are specifically associated with lung cancer risk among this minority subgroup. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-400.