Irina Mordukhovich

Association between long-term exposure to traffic particles and blood pressure in the Veterans Administration Normative Aging Study

Objectives Particulate air pollution is associated with cardiovascular events, but the mechanisms are not fully understood. The main objective was to assess the relationship between long-term exposure to traffic-related air pollution and blood pressure (BP). Methods The authors used longitudinal data from 853 elderly men participating in the Veterans Administration Normative Aging Study, followed during 1996–2008. Long-term average exposures to traffic particles were created from daily predictions of black carbon (BC) exposure at the geocoded address of each subject, using a validated spatiotemporal model based on ambient monitoring at 82 Boston-area locations. The authors examined the association of these exposures with BP using a mixed model. The authors included the following covariates: age, body mass index, smoking, alcohol, fasting glucose, creatinine clearance, use of cardiovascular medication, education, census-level poverty, day of week and season of clinical visit. Results The authors found significant positive associations between 1-year average BC exposure and both systolic and diastolic blood pressure. An IQR increase in 1-year average BC exposure (0.32 μg/m3) was associated with a 2.64 mm Hg increase in systolic blood pressure (95% CI 1.47 to 3.80) and a 2.41 mm Hg increase in diastolic blood pressure (95% CI 1.77 to 3.05). Conclusions Long-term exposure to traffic particles is associated with increased BP, which may explain part of the association with myocardial infarctions and cardiovascular deaths reported in cohort studies.

Associations of toenail arsenic, cadmium, mercury, manganese, and lead with blood pressure in the normative aging study

Background: Arsenic, cadmium, mercury, and lead are associated with cardiovascular disease in epidemiologic research. These associations may be mediated by direct effects of the metals on blood pressure (BP) elevation. Manganese is associated with cardiovascular dysfunction and hypotension in occupational cohorts. Objectives: We hypothesized that chronic arsenic, cadmium, mercury, and lead exposures elevate BP and that manganese lowers BP. Methods: We conducted a cross-sectional analysis of associations between toenail metals and BP among older men from the Normative Aging Study (n = 639), using linear regression and adjusting for potential confounders. Results: An interquartile range increase in toenail arsenic was associated with higher systolic BP [0.93 mmHg; 95% confidence interval (CI): 0.25, 1.62] and pulse pressure (0.76 mmHg; 95% CI: 0.22, 1.30). Positive associations between arsenic and BP and negative associations between manganese and BP were strengthened in models adjusted for other toenail metals. Conclusions: Our findings suggest associations between BP and arsenic and manganese. This may be of public health importance because of prevalence of both metal exposure and cardiovascular disease. Results should be interpreted cautiously given potential limitations of toenails as biomarkers of metal exposure.

A review of African American-white differences in risk factors for cancer: prostate cancer

ObjectiveAfrican American men have higher prostate cancer incidence rates than White men, for reasons not completely understood. This review summarizes the existing literature of race-specific associations between risk factors and prostate cancer in order to examine whether associations differ.MethodsWe reviewed epidemiologic studies published between January 1970 and December 2008 that reported race-specific effect estimates. We focused mainly on modifiable risk factors related to lifestyle and health. A total of 37 articles from 21 study populations met our inclusion criteria.ResultsWe found no evidence of racial differences in associations between prostate cancer and alcohol intake, tobacco use, and family history of prostate cancer. Research suggests that a modest positive association may exist between height and prostate cancer risk (all prostate cancer and advanced prostate cancer) among Whites only. No clear patterns were observed for associations with physical activity, weight/body mass index, dietary factors, occupational history, sexual behavior, sexually transmissible infections, and other health conditions.DiscussionOur results suggest few differences in prostate cancer risk factors exist between racial groups and underscore areas where additional research is needed. Future studies should enroll higher numbers of African American participants and report results for advanced prostate cancer.

Associations between Polycyclic Aromatic Hydrocarbon–Related Exposures and p53 Mutations in Breast Tumors

Background Previous studies have suggested that polycyclic aromatic hydrocarbons (PAHs) may be associated with breast cancer. However, the carcinogenicity of PAHs on the human breast remains unclear. Certain carcinogens may be associated with specific mutation patterns in the p53 tumor suppressor gene, thereby contributing information about disease etiology. Objectives We hypothesized that associations of PAH-related exposures with breast cancer would differ according to tumor p53 mutation status, effect, type, and number. Methods We examined this possibility in a population-based case–control study using polytomous logistic regression. As previously reported, 151 p53 mutations among 859 tumors were identified using Surveyor nuclease and confirmed by sequencing. Results We found that participants with p53 mutations were less likely to be exposed to PAHs (assessed by smoking status in 859 cases and 1,556 controls, grilled/smoked meat intake in 822 cases and 1,475 controls, and PAH–DNA adducts in peripheral mononuclear cells in 487 cases and 941 controls) than participants without p53 mutations. For example, active and passive smoking was associated with p53 mutation–negative [odds ratio (OR) = 1.55; 95% confidence interval (CI), 1.11–2.15] but not p53 mutation–positive (OR = 0.77; 95% CI, 0.43–1.38) cancer (ratio of the ORs = 0.50, p < 0.05). However, frameshift mutations, mutation number, G:C→A:T transitions at CpG sites, and insertions/deletions were consistently elevated among exposed subjects. Conclusions These findings suggest that PAHs may be associated with specific breast tumor p53 mutation subgroups rather than with overall p53 mutations and may also be related to breast cancer through mechanisms other than p53 mutation.

Vehicular Traffic-Related Polycyclic Aromatic Hydrocarbon Exposure and Breast Cancer Incidence: The Long Island Breast Cancer Study Project (LIBCSP).

Background Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants, known human lung carcinogens, and potent mammary carcinogens in laboratory animals. However, the association between PAHs and breast cancer in women is unclear. Vehicular traffic is a major ambient source of PAH exposure. Objectives Our study aim was to evaluate the association between residential exposure to vehicular traffic and breast cancer incidence. Methods Residential histories of 1,508 participants with breast cancer (case participants) and 1,556 particpants with no breast cancer (control participants) were assessed in a population-based investigation conducted in 1996–1997. Traffic exposure estimates of benzo[a]pyrene (B[a]P), as a proxy for traffic-related PAHs, for the years 1960–1995 were reconstructed using a model previously shown to generate estimates consistent with measured soil PAHs, PAH–DNA adducts, and CO readings. Associations between vehicular traffic exposure estimates and breast cancer incidence were evaluated using unconditional logistic regression. Results The odds ratio (95% CI) was modestly elevated by 1.44 (0.78, 2.68) for the association between breast cancer and long-term 1960–1990 vehicular traffic estimates in the top 5%, compared with below the median. The association with recent 1995 traffic exposure was elevated by 1.14 (0.80, 1.64) for the top 5%, compared with below the median, which was stronger among women with low fruit/vegetable intake [1.46 (0.89, 2.40)], but not among those with high fruit/vegetable intake [0.92 (0.53, 1.60)]. Among the subset of women with information regarding traffic exposure and tumor hormone receptor subtype, the traffic–breast cancer association was higher for those with estrogen/progesterone-negative tumors [1.67 (0.91, 3.05) relative to control participants], but lower among all other tumor subtypes [0.80 (0.50, 1.27) compared with control participants]. Conclusions In our population-based study, we observed positive associations between vehicular traffic-related B[a]P exposure and breast cancer incidence among women with comparatively high long-term traffic B[a]P exposures, although effect estimates were imprecise. Citation Mordukhovich I, Beyea J, Herring AH, Hatch M, Stellman SD, Teitelbaum SL, Richardson DB, Millikan RC, Engel LS, Shantakumar S, Steck SE, Neugut AI, Rossner P Jr., Santella RM, Gammon MD. 2016. Vehicular traffic–related polycyclic aromatic hydrocarbon exposure and breast cancer incidence: the Long Island Breast Cancer Study Project (LIBCSP). Environ Health Perspect 124:30–38; http://dx.doi.org/10.1289/ehp.1307736

Association Between Low-Level Environmental Arsenic Exposure and QT Interval Duration in a General Population Study

High-level arsenic exposure is consistently associated with QT prolongation, a risk factor for arrhythmia and sudden cardiac death. Arsenic may act on QT by increasing cardiac calcium currents. The authors hypothesized that low-level arsenic exposure would be associated with QT duration and that this effect would be stronger among persons not using calcium channel blockers. They performed a cross-sectional analysis in elderly men from the Normative Aging Study to analyze associations between toenail arsenic and QT and heart rate-corrected QT (QTc) durations and to examine effect modification by calcium channel blocker use, using linear regression and adjusting for potential confounders. Participants were examined in Boston, Massachusetts, between 2000 and 2002 or in 2006. An interquartile range increase in arsenic concentration was associated with a 3.8-millisecond increase in QT (95% confidence interval: 0.82, 6.8) and a 2.5-millisecond increase in QTc (95% confidence interval: 0.11, 4.9). There was no evidence of effect modification by medication use for either QT (P = 0.93) or QTc (P = 0.58). The authors observed positive associations between a biomarker of arsenic exposure and QT duration but found no evidence of effect modification by calcium channel blocker use, possibly because of modest power.

Exposure to multiple sources of polycyclic aromatic hydrocarbons and breast cancer incidence

BACKGROUND Despite studies having consistently linked exposure to single-source polycyclic aromatic hydrocarbons (PAHs) to breast cancer, it is unclear whether single sources or specific groups of PAH sources should be targeted for breast cancer risk reduction. OBJECTIVES This study considers the impact on breast cancer incidence from multiple PAH exposure sources in a single model, which better reflects exposure to these complex mixtures. METHODS In a population-based case-control study conducted on Long Island, New York (N=1508 breast cancer cases/1556 controls), a Bayesian hierarchical regression approach was used to estimate adjusted posterior means and credible intervals (CrI) for the adjusted odds ratios (ORs) for PAH exposure sources, considered singly and as groups: active smoking; residential environmental tobacco smoke (ETS); indoor and outdoor air pollution; and grilled/smoked meat intake. RESULTS Most women were exposed to PAHs from multiple sources, and the most common included active/passive smoking and grilled/smoked food intake. In multiple-PAH source models, breast cancer incidence was associated with residential ETS from a spouse (OR=1.20, 95%CrI=1.03, 1.40) and synthetic firelog burning (OR=1.29, 95%CrI=1.06, 1.57); these estimates are similar, but slightly attenuated, to those from single-source models. Additionally when we considered PAH exposure groups, the most pronounced significant associations included total indoor sources (active smoking, ETS from spouse, grilled/smoked meat intake, stove/fireplace use, OR=1.45, 95%CrI=1.02, 2.04). CONCLUSIONS Groups of PAH sources, particularly indoor sources, were associated with a 30-50% increase in breast cancer incidence. PAH exposure is ubiquitous and a potentially modifiable breast cancer risk factor.

Sources of polycyclic aromatic hydrocarbons are associated with gene-specific promoter methylation in women with breast cancer

BACKGROUND Tobacco smoke, diet and indoor/outdoor air pollution, all major sources of polycyclic aromatic hydrocarbons (PAHs), have been associated with breast cancer. Aberrant methylation may be an early event in carcinogenesis, but whether PAHs influence the epigenome is unclear, particularly in breast tissue where methylation may be most relevant. We aimed to evaluate the role of methylation in the association between PAHs and breast cancer. METHODS In a population-based case-control study, we measured promoter methylation of 13 breast cancer-related genes in breast tumor tissue (n=765-851 cases) and global methylation in peripheral blood (1055 cases/1101 controls). PAH sources (current active smoking, residential environmental tobacco smoke (ETS), vehicular traffic, synthetic log burning, and grilled/smoked meat intake) were evaluated separately. Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS When comparing methylated versus unmethylated genes, synthetic log use was associated with increased ORs for CDH1 (OR=2.26, 95%CI=1.06-4.79), HIN1 (OR=2.14, 95%CI=1.34-3.42) and RARβ (OR=1.80, 95%CI=1.16-2.78) and decreased ORs for BRCA1 (OR=0.44, 95%CI=0.30-0.66). Residential ETS was associated with decreased ORs for ESR1 (OR=0.74, 95%CI=0.56-0.99) and CCND2 methylation (OR=0.65, 95%CI=0.44-0.96). Current smoking and vehicular traffic were associated with decreased ORs for DAPK (OR=0.53, 95%CI=0.28-0.99) and increased ORs for TWIST1 methylation (OR=2.79, 95%CI=1.24-6.30), respectively. In controls, synthetic log use was inversely associated with LINE-1 (OR=0.59, 95%CI=0.41-0.86). DISCUSSION PAH sources were associated with hypo- and hypermethylation at multiple promoter regions in breast tumors and LINE-1 hypomethylation in blood of controls. Methylation may be a potential biologic mechanism for the associations between PAHs and breast cancer incidence.

Association Between Particulate Air Pollution and QT Interval Duration in an Elderly Cohort.

Background: Short-term fine particulate matter (PM2.5) exposure has been linked with increased QT interval duration, a marker of ventricular repolarization and a risk factor for cardiac arrhythmia and sudden death, in several studies. Only one previous study evaluated whether long-term PM exposure is related to the QT interval. We aim to evaluate whether subchronic and long-term exposure to PM2.5 at home is linked with QT duration in an elderly cohort. Methods: We measured heart-rate corrected QT interval duration among 404 participants from the Greater Boston area between 2003 and 2011. We modeled residential PM2.5 exposures using a hybrid satellite- and land use-based model. We evaluated associations between moving averages of short-term (1–2 days), subchronic (3–28 days), and long-term (1 year) pollutant exposures and corrected QT duration using linear mixed models. We also evaluated effect modification by oxidative stress genetic score using separated regression models and interaction terms. Results: We observed positive associations between subchronic and long-term PM2.5 exposure and corrected QT duration, with the strongest results for longer-term exposures. For example, a one standard deviation increase in 1-year PM2.5 was associated with a 6.3 ms increase in corrected QT (95% confidence interval: 1.8, 11). We observed somewhat greater effects among subjects with higher (8.5 ms) rather than lower (3.1 ms) oxidative stress allelic profiles (P interaction = 0.25). Conclusions: PM2.5 was associated with increased corrected QT duration in an elderly cohort. While most previous studies focused on short-term air pollution exposures, our results suggest that longer-term exposures are associated with cardiac repolarization.

Indoor air pollution exposure from use of indoor stoves and fireplaces in association with breast cancer: a case-control study

BackgroundPrevious studies suggest that polycyclic aromatic hydrocarbons (PAHs) may adversely affect breast cancer risk. Indoor air pollution from use of indoor stoves and/or fireplaces is an important source of ambient PAH exposure. However, the association between indoor stove/fireplace use and breast cancer risk is unknown. We hypothesized that indoor stove/fireplace use in a Long Island, New York study population would be positively associated with breast cancer and differ by material burned, and the duration and timing of exposure. We also hypothesized that the association would vary by breast cancer subtype defined by p53 mutation status, and interact with glutathione S-transferases GSTM1, T1, A1 and P1 polymorphisms.MethodsPopulation-based, case-control resources (1,508 cases/1,556 controls) were used to conduct unconditional logistic regression to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI).ResultsBreast cancer risk was increased among women reporting ever burning synthetic logs (which may also contain wood) in their homes (OR = 1.42, 95% CI 1.11, 1.84), but not for ever burning wood alone (OR = 0.93, 95% CI 0.77, 1.12). For synthetic log use, longer duration >7 years, older age at exposure (>20 years; OR = 1.65, 95% CI 1.02, 2.67) and 2 or more variants in GSTM1, T1, A1 or P1 (OR = 1.71, 95% CI 1.09, 2.69) were associated with increased risk.ConclusionsBurning wood or synthetic logs are both indoor PAH exposure sources; however, positive associations were only observed for burning synthetic logs, which was stronger for longer exposures, adult exposures, and those with multiple GST variant genotypes. Therefore, our results should be interpreted with care and require replication.