Background: The metabolome is a collection of exogenous chemicals and metabolites from cellular processes that may reflect the body's response to environmental exposures. Studies of air pollution and metabolomics are limited. Objectives: To explore changes in the human metabolome before, during, and after the 2008 Beijing Olympics Games, when air pollution was high, low, and high, respectively. Methods: Serum samples were collected before, during, and after the Olympics from 26 participants in an existing panel study. Gas and ultra-high performance liquid chromatography/mass spectrometry were used in metabolomics analysis. Repeated measures ANOVA, network analysis, and enrichment analysis methods were employed to identify metabolites and classes associated with air pollution changes. Results: A total of 886 molecules were measured in our metabolomics analysis. Network partitioning identified four modules with 65 known metabolites that significantly changed across the three time points. All known molecules in the first module (n=33) were lipids (e.g., eicosapentaenoic acid, stearic acid). The second module consisted primarily of dipeptides (n=24, e.g., isoleucylglycine) plus 8 metabolites from four other classes (e.g., hypoxanthine, 12-hydroxyeicosatetraenoic acid). Most of the metabolites in Modules 3 (19 of 23) and 4 (5 of 5) were unknown. Enrichment analysis of module-identified metabolites indicted significantly overrepresented pathways, including long- and medium-chain fatty acids, polyunsaturated fatty acids (n3 and n6), eicosanoids, lysolipid, dipeptides, fatty acid metabolism, and purine metabolism [(hypo) xanthine/inosine–containing pathways]. Conclusions: We identified two major metabolic signatures: one consisting of lipids, and a second that included dipeptides, polyunsaturated fatty acids, taurine, and xanthine. Metabolites in both groups decreased during the 2008 Beijing Olympics, when air pollution was low, and increased after the Olympics, when air pollution returned to normal (high) levels. https://doi.org/10.1289/EHP3705
2183 Polycyclic aromatic hydrocarbons (PAHs) are an important component of air pollution and potential human carcinogens. While they have been shown to cause mammary cancer in animal studies, the association between PAH exposure and breast cancer risk is not well understood. Traffic emissions are one of the major sources of PAH exposure in cities. Further, growing evidence suggests that there may be critical time periods of exposure in breast cancer initiation and development. In this study, we examined the association between breast cancer risk and exposure to PAHs from traffic emissions estimated for each woman at menarche, at the time when she had her first pregnancy and birth, and at 20 and 10 years prior to interview, using data collected from the Western New York Exposures and Breast Cancer (WEB) study, a population based case control study in western New York. All participants were women, aged 35-79, residents of Erie and Niagara Counties. Cases had incident, primary, histologically-confirmed breast cancer. Controls were randomly selected and frequency-matched to cases on age, race and county. In-person interviews were used to collect data on potential breast cancer risk factors including self-reported lifetime residential history. Traffic volumes on roads were obtained from historical records for the years from 1960-2002. Tailpipe emission data were based on previous reports, including measurements carried out in tunnels or on individual vehicles run in place on test beds. A geographic model, developed by Dr. Beyea and colleagues from the Long Island Breast Cancer project, was used to reconstruct historical traffic PAHs, using BaP as a surrogate for total PAH exposure. Cruise emissions, cold engine emissions and intersection emissions were used to estimate total traffic PAH emissions. Meteorological information was also utilized in the geographic dispersion model to assign PAH exposure at each residence. The model was validated using data collected from both Long Island and our study area. We found evidence that higher exposure to traffic PAH emissions at menarche was associated with increased risk of premenopausal breast cancer (OR 2.07, 95% CI 0.91-4.72, p for trend 0.03) and emissions at the time of a woman’s first birth was associated with postmenopausal breast cancer (OR 2.58, 95% CI 1.15-5.83, p for trend 0.19). Both associations were limited to lifetime non-smokers. There was no association of traffic emissions with risk for any of the other time periods. These findings provide evidence for both the potential importance of early exposures and the potential importance of an environmental agent in risk of breast cancer.
The lung cancer mortality rate in Xuan Wei County is among the highest in China and has been attributed to exposure to indoor smoky coal emissions that contain very high levels of polycyclic aromatic hydrocarbons (PAHs). Nucleotide excision repair (NER) plays a key role in reversing DNA damage from exposure to environmental carcinogens, such as PAHs, that form bulky DNA adducts. We studied single nucleotide polymorphisms (SNPs) and their corresponding haplotypes in 6 genes (ERCC1, ERCC2/XPD, ERCC4/XPF, ERCC5/XPG, RAD23B and XPC) involved in NER in a population-based case-control study of lung cancer in Xuan Wei. A total of 122 incident primary lung cancer cases and 122 individually matched controls were enrolled. Three linked SNPs in ERCC2 were associated with lung cancer with similar ORs; e.g., persons with the Gln allele at codon 751 had a 60% reduction of lung cancer (OR = 0.40, 95% CI 0.18-0.89). Moreover, one haplotype in ERCC2 was associated with a decreased risk of lung cancer (OR = 0.40, 95% CI 0.19-0.85) compared to the most common haplotype. In addition, subjects with one or 2 copies of the Val allele at codon 249 of RAD23B had a 2-fold increased risk of lung cancer (OR = 1.91, 95% CI 1.12-3.24). In summary, our results suggest that genetic variants in genes involved in the NER pathway may play a role in lung cancer susceptibility in Xuan Wei. However, due to the small sample size, additional studies are needed to evaluate these associations within Xuan Wei and in other populations with substantial environmental exposure to PAHs.
Abstract Background: Polychlorinated biphenyls (PCBs) exposure is associated with increased risk of melanoma and non-Hodgkin lymphoma in some, but not all, epidemiologic studies. Although the carcinogenic mechanisms of specific PCB congeners remain to be fully explained, PCBs have been demonstrated to induce oxidative stress and inflammation and therefore may have deleterious impacts on telomere length. We investigated the association between serum concentrations of PCBs and telomere length in a highly exposed population. Methods: The Anniston Community Health Survey (ACHS) is a cross-sectional study of 766 residents of Anniston, Alabama conducted between 2005 and 2007. We measured relative telomere length (RTL) with telomere/single copy gene ratio, in DNA extracted from peripheral blood samples in a subset of 57 African-American and 46 white participants, using monochrome multiplex quantitative polymerase chain reaction. We used multiple linear regression to estimate the association between 27 individual PCB congeners, and sum PCBs, adjusting for age, plate, and total lipids. All analyses were stratified by race. PCBs and RTL were log-transformed. Results: ACHS participants had high serum concentrations of PCBs (mean sum PCBs among African-Americans = 14,687.69 ppt whole weight, SD = 23,515.46; mean sum PCBs white participants 6,088.32 ppt whole weight, SD = 8,750.57). RTL did not differ by race (mean RTL African-Americans = 0.94 SD = 0.08; mean RTL whites = 0.94, SD = 0.09). Among African-American participants, sum serum PCBs was not associated with RTL (0.70% per 100 ppt; 95% confidence interval = -9.43, 19.70). However, PCB 167 was weakly associated with higher RTL (2.35%, 95%CI = -8.56, 14.55), while PCB 157 was associated with shorter RTL (-4.36%; 95%CI = -15.63, 8.40). Among white participants, a 100 ppt increase in sum serum PCBs was associated with a 10.20% increase in RTL (95% CI = -7.10, 30.72). PCB 138, in particular, was associated with increased RTL among white participants (16.29%; 95% CI = 1.34, 33.46). Conversely, PCB 189 was associated with shorter RTL among white participants (-10.48%; 95%CI = -29.82, 14.19). Conclusions: We did not observe consistent associations between serum concentrations of PCBs and RTL, suggesting that the association may vary by race and be congener specific. Our results are necessarily preliminary and are limited by the small number of participants. Additional measurements of RTL among ACHS participants are on-going. Citation Format: Catherine Callahan, Marian Pavuk, Xuefeng Ren, James R. Olson, Matthew R. Bonner. Polychlorinated biphenyls and relative telomere length in the Anniston Community Health Survey: A cross-sectional study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3456.
Ambient air pollution is classified as a human carcinogen by the International Agency for Research on Cancer (IARC). However, epidemiologic studies supporting this classification have focused on lung cancer mortality rather than incidence, and spatial and temporal resolutions of exposure estimates have varied considerably across studies.We evaluated the association of outdoor air pollution and lung cancer incidence among never-smoking participants of the Women's Health Initiative (WHI) study, a large, US-based cohort of postmenopausal women (N = 65,419; 265 cases). We used geospatial models to estimate exposures to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) based on residential addresses at baseline and throughout follow-up. We also characterized exposures to traffic-related air pollution by proximity to major roadways. We estimated hazard ratios (HRs) for the risk of lung cancer in association with these exposure metrics using Cox proportional hazards regression models.No compelling associations of PM2.5 and NO2 exposures with lung cancer risk were observed. An increased risk of lung cancer was observed when comparing those individuals with residences <50 versus ≥200 meters from a primary limited access highway (HR = 5.23; 95% confidence interval = 1.94, 14.13).Our results do not exclude lung cancer risk estimates observed in association with PM2.5 and NO2 exposures identified in previous studies. Our results suggest that residential proximity to major roadways may be a proxy for carcinogenic exposures not correlated with PM2.5 or NO2 levels. New studies of air pollution and lung cancer incidence should characterize additional aspects of proximity to major roadways.
Abstract Background Growing laboratory and animal model evidence supports the potentially carcinogenic effects of some phthalates, chemicals used as plasticizers in a wide variety of consumer products, including cosmetics, medications, and vinyl flooring. However, prospective data on whether phthalates are associated with human breast cancer risk are lacking. Methods We conducted a nested case-control study within the Women’s Health Initiative (WHI) prospective cohort (n = 419 invasive case subjects and 838 control subjects). Control subjects were matched 2:1 to case subjects on age, enrollment date, follow-up time, and WHI study group. We quantified 13 phthalate metabolites and creatinine in two or three urine samples per participant over one to three years. Multivariable conditional logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for breast cancer risk associated with each phthalate biomarker up to 19 years of follow-up. Results Overall, we did not observe statistically significant positive associations between phthalate biomarkers and breast cancer risk in multivariable analyses (eg, 4th vs 1st quartile of diethylhexyl phthalate, OR = 1.03, 95% CI = 0.91 to 1.17). Results were generally similar in analyses restricted to disease subtypes, to nonusers of postmenopausal hormone therapy, stratified by body mass index, or to case subjects diagnosed within three, five, or ten years. Conclusions In the first prospective analysis of phthalates and postmenopausal breast cancer, phthalate biomarker concentrations did not result in an increased risk of developing invasive breast cancer.
Abstract Background Adolescents are engaged in agricultural work, including pesticide application, around the world. Adolescent pesticide applicators are more likely to be exposed to pesticides than their adult counterparts because of their application practice and hygiene habits surrounding pesticide use. There is a need for low-cost interventions to reduce pesticide exposure. We evaluated a theoretically-based educational intervention to change perceptions about the risk of pesticide use and hygiene habits during and after pesticide application for adolescent and young adult pesticide applicators in Egypt. Methods Young adult and adolescent male pesticide applicators were given a one-hour educational intervention to inform them about the risk of pesticide use and how to reduce pesticide exposure. The median age of participants was 18 years old. Changes in perceived susceptibility and effectiveness were measured with a survey pre and post-intervention ( n = 119) on the same day. The same survey ( n = 95) was given 8-months post-intervention to identify sustained effects. Observational checklists of pesticide application practice were also completed during application seasons before and after the intervention. Results There was an increase in the proportion of individuals who viewed pesticides as being a long-term health risk (74.7% pre-intervention to 97.9% post-intervention, McNemar test p < 0.001). This change remained significant when surveyed at the 8-month follow-up (90.5%, p < 0.001). There was also a sustained improvement regarding participants’ views of proper hygiene practice surrounding pesticide application. Applicators were observed wearing goggles, shoes, and masks more frequently post-intervention. Conclusion This theoretically-based intervention is an example of a low-cost solution that can improve adolescents’ and young adults’ practices regarding pesticide application and personal hygiene practices during and after pesticide application. The intervention can be applied in other countries with similar safety culture surrounding pesticide application.
