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

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.

Assessing environmental and occupational risk factors for lung cancer in Mexican-Americans.

BACKGROUND: We investigated environmental and occupational exposures and smoking history (while controlling for demographics) in a population of Mexican-American lung cancer cases and controls from the Houston metropolitan area. METHODS: Data were collected between 1991 and 2005 as part of an on-going multi-racial/ethnic, lung cancer case-control study. Cases included 212 Mexican-American lung cancer cases from UT MD Anderson Cancer Center. Controls (n = 328) were recruited from Houston's largest multispecialty group practice and frequency matched to the cases by age (± 5 years), sex, and ethnicity. Environmental and occupational factors were analyzed and odds ratios and 95% confidence intervals were calculated using logistic regression. RESULTS: We detected elevated risks of lung cancer associated with pesticide exposure and found conventional and antimicrobial (e.g., sterilizers, disinfectants, antiseptics) pesticides 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; antimicrobial 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 pesticides, we could not identify individual pesticides. Our findings are an important preliminary step in identifying factors that are specifically associated with lung cancer risk among Mexican Americans.

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.

Prevalence of asthma by industry and occupation in the U.S. working population.

BACKGROUND: Workers are potentially exposed to asthmagens daily. Our study was conducted to estimate the prevalence of asthma among working adults in the U.S. by industry and occupation. METHODS: Using data from the National Health and Nutrition Examination Survey (2001-2004), multiple logistic regression was used to investigate associations between industry and occupation and current asthma as defined by positive responses to "Has a doctor or other health professional ever told you that you have asthma?" and "Do you still have asthma?" RESULTS: Workers in mining (17.0%), health-related industries (12.5%), teaching (13.1%), or in health-related occupations (12.6%) had the highest prevalence of asthma. As compared to construction industry workers, workers in mining (aOR = 5.2, 95% CI: 1.1-24.2) or health-related (aOR = 2.3, 95% CI: 1.1-4.8) industries had significantly higher odds of asthma. CONCLUSION: Our study adds to the increasing evidence that miners, healthcare workers and teachers remain high-risk working populations and appropriate evaluation and control measures are needed to protect these workers.

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.

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.

Genome-wide Gene-Asbestos Exposure Interaction Association Study Identifies a Common Susceptibility Variant on 22q13.31 Associated with Lung Cancer Risk.

BACKGROUND: Occupational asbestos exposure has been found to increase lung cancer risk in epidemiologic studies. METHODS: We conducted an asbestos exposure-gene interaction analyses among several Caucasian populations who were current or ex-smokers. The discovery phase included 833 Caucasian cases and 739 Caucasian controls, and used a genome-wide association study (GWAS) to identify single-nucleotide polymorphisms (SNP) with gene-asbestos interaction effects. The top ranked SNPs from the discovery phase were replicated within the International Lung and Cancer Consortium (ILCCO). First, in silico replication was conducted in those groups that had GWAS and asbestos exposure data, including 1,548 cases and 1,527 controls. This step was followed by de novo genotyping to replicate the results from the in silico replication, and included 1,539 cases and 1,761 controls. Multiple logistic regression was used to assess the SNP-asbestos exposure interaction effects on lung cancer risk. RESULTS: We observed significantly increased lung cancer risk among MIRLET7BHG (MIRLET7B host gene located at 22q13.31) polymorphisms rs13053856, rs11090910, rs11703832, and rs12170325 heterozygous and homozygous variant allele(s) carriers (P < 5 × 10(-7) by likelihood ratio test; df = 1). Among the heterozygous and homozygous variant allele(s) carriers of polymorphisms rs13053856, rs11090910, rs11703832, and rs12170325, each unit increase in the natural log-transformed asbestos exposure score was associated with age-, sex-, smoking status, and center-adjusted ORs of 1.34 [95% confidence interval (CI), 1.18-1.51], 1.24 (95% CI, 1.14-1.35), 1.28 (95% CI, 1.17-1.40), and 1.26 (95% CI, 1.15-1.38), respectively, for lung cancer risk. CONCLUSION: Our findings suggest that MIRLET7BHG polymorphisms may be important predictive markers for asbestos exposure-related lung cancer. IMPACT: To our knowledge, our study is the first report using a systematic genome-wide analysis in combination with detailed asbestos exposure data and replication to evaluate asbestos-associated lung cancer risk.

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 (I(2) = 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.

Self-reported prior lung diseases as risk factors for non-small cell lung cancer in Mexican Americans.

This study was conducted to assess the association between prior history of respiratory disease and lung cancer among Mexican Americans using data from a multi-racial/ethnic lung cancer case-control study. Cases (n = 204) were patients with previously untreated lung cancer. Healthy control participants (n = 325) were recruited from a large physician group practice. Demographics, cigarette use, and history of respiratory disease were collected. Multivariable logistic regression models were used to estimate relative risk. Prior history of COPD (OR = 2.0; 95 % CI 1.2-3.3) and pneumonia (OR = 2.2; 95 % CI 1.3-3.6) were associated with an increased risk of lung cancer. These findings illustrate that prior COPD and pneumonia are associated with an increased risk of lung cancer among Mexican Americans. To our knowledge, this is one of largest case-control analyses assessing the role of respiratory disease and lung cancer risk specifically among Mexican-Americans.

Perspective: publication ethics and the emerging scientific workforce: understanding "plagiarism" in a global context.

English has long been the dominant language of scientific publication, and it is rapidly approaching near-complete hegemony. The majority of the scientists publishing in English-language journals are not native English speakers, however. This imbalance has important implications for training concerning ethics and enforcement of publication standards, particularly with respect to plagiarism. The authors suggest that lack of understanding of what constitutes plagiarism and the use of a linguistic support strategy known as "patchwriting" can lead to inadvertent misuse of source material by nonnative speakers writing in English as well as to unfounded accusations of intentional scientific misconduct on the part of these authors. They propose that a rational and well-informed dialogue about this issue is needed among editors, educators, administrators, and both native-English-speaking and nonnative-English-speaking writers. They offer recommendations for creating environments in which such dialogue and training can occur.

The advantage of imputation of missing income data to evaluate the association between income and self-reported health status (SRH) in a Mexican American cohort study.

Missing data often occur in cross-sectional surveys and longitudinal and experimental studies. The purpose of this study was to compare the prediction of self-rated health (SRH), a robust predictor of morbidity and mortality among diverse populations, before and after imputation of the missing variable "yearly household income." We reviewed data from 4,162 participants of Mexican origin recruited from July 1, 2002, through December 31, 2005, and who were enrolled in a population-based cohort study. Missing yearly income data were imputed using three different single imputation methods and one multiple imputation under a Bayesian approach. Of 4,162 participants, 3,121 were randomly assigned to a training set (to derive the yearly income imputation methods and develop the health-outcome prediction models) and 1,041 to a testing set (to compare the areas under the curve (AUC) of the receiver-operating characteristic of the resulting health-outcome prediction models). The discriminatory powers of the SRH prediction models were good (range, 69-72%) and compared to the prediction model obtained after no imputation of missing yearly income, all other imputation methods improved the prediction of SRH (P < 0.05 for all comparisons) with the AUC for the model after multiple imputation being the highest (AUC = 0.731). Furthermore, given that yearly income was imputed using multiple imputation, the odds of SRH as good or better increased by 11% for each $5,000 increment in yearly income. This study showed that although imputation of missing data for a key predictor variable can improve a risk health-outcome prediction model, further work is needed to illuminate the risk factors associated with SRH.