Black Carbon Exposure, Oxidative Stress Genes, and Blood Pressure in a Repeated-Measures Study

BACKGROUND. Particulate matter (PM) air pollution has been associated with cardiovascular morbidity and mortality, and elevated blood pressure (BP) is a known risk factor for cardiovascular disease. A small number of studies have investigated the relationship between PM and BP and found mixed results. Evidence suggests that traffic-related air pollution contributes significantly to PM-related cardiovascular effects. OBJECTIVES. We hypothesized that black carbon (BC), a traffic-related combustion by-product, would be more strongly associated with BP than would fine PM [aerodynamic diameter ≤ 2.5 μm (PM2.5)], a heterogeneous PM mixture, and that these effects would be larger among participants with genetic variants associated with impaired antioxidative defense. METHODS. We performed a repeated-measures analysis in elderly men to analyze associations between PM2.5 and BC exposure and BP using mixed-effects models with random intercepts, adjusting for potential confounders. We also examined statistical interaction between BC and genetic variants related to oxidative stress defense: GSTM1, GSTP1, GSTT1, NQO1, catalase, and HMOX-1. RESULTS. A 1-SD increase in BC concentration was associated with a 1.5-mmHg increase in systolic BP [95% confidence interval (CI), 0.1-2.8] and a 0.9-mmHg increase in diastolic BP (95% CI, 0.2-1.6). We observed no evidence of statistical interaction between BC and any of the genetic variants examined and found no association between PM2.5 and BP. CONCLUSIONS. We observed positive associations between BP and BC, but not between BP and PM2.5, and found no evidence of effect modification of the association between BC and BP by gene variants related to antioxidative defense.National Institute of Environmental Health Sciences (ES015172, ES014663); National Cancer Institute (2-T32-CA009330); United States Environmental Protection Agency (R832416); United States Deparment of Veterans Affairs; Massachusetts Veterans Epidemiology Research and Information Cente

Particulate Air Pollution, Oxidative Stress Genes, and Heart Rate Variability in an Elderly Cohort

Background and Objectives: We have previously shown that reduced defenses against oxidative stress due to glutathione S-transferase M1 (GSTM1) deletion modify the effects of PM[2.5] (fine-particulate air pollution of < 2.5 μm in aerodynamic diameter) on heart rate variability (HRV) in a cross-sectional analysis of the Normative Aging Study, an elderly cohort. We have extended this to include a longitudinal analysis with more subjects and examination of the GT short tandem repeat polymorphism in the heme oxygenase-1 (HMOX-1) promoter. Methods: HRV measurements were taken on 539 subjects. Linear mixed effects models were fit for the logarithm of HRV metrics—including standard deviation of normal-to-normal intervals (SDNN), high frequency (HF), and low frequency (LF)—and PM2.5 concentrations in the 48 hr preceding HRV measurement, controlling for confounders and a random subject effect. Results: PM2.5 was significantly associated with SDNN (p = 0.04) and HF (p = 0.03) in all subjects. There was no association in subjects with GSTM1, whereas there was a significant association with SDNN, HF, and LF in subjects with the deletion. Similarly, there was no association with any HRV measure in subjects with the short repeat variant of HMOX-1, and significant associations in subjects with any long repeat. We found a significant three-way interaction of PM[2.5] with GSTM1 and HMOX-1 determining SDNN (p = 0.008), HF (p = 0.01) and LF (p = 0.04). In subjects with the GSTM1 deletion and the HMOX-1 long repeat, SDNN decreased by 13% [95% confidence interval (CI), −21% to −4%], HF decreased by 28% (95% CI, −43% to −9%), and LF decreased by 20% (95% CI, −35% to −3%) per 10 μg/m3 increase in PM. Conclusions: Oxidative stress is an important pathway for the autonomic effects of particles

Polymorphisms in Nucleotide Excision Repair Genes, Arsenic Exposure, and Non-Melanoma Skin Cancer in New Hampshire

Background: Arsenic exposure may alter the efficiency of DNA repair. UV damage is specifically repaired by nucleotide excision repair (NER), and common genetic variants in NER may increase risk for non-melanoma skin cancer (NMSC). Objective: We tested whether polymorphisms in the NER genes XPA (A23G) and XPD (Asp312Asn and Lys751Gln) modify the association between arsenic and NMSC. Methods: Incident cases of basal and squamous cell carcinoma (BCC and SCC, respectively) were identified through a network of dermatologists and pathology laboratories across New Hampshire. Population-based controls were frequency matched to cases on age and sex. Arsenic exposure was assessed in toenail clippings. The analysis included 880 cases of BCC, 666 cases of SCC, and 780 controls. Results: There was an increased BCC risk associated with high arsenic exposure among those homozygous variant for XPA [odds ratio (OR) = 1.8; 95% confidence interval (CI), 0.9–3.7]. For XPD, having variation at both loci (312Asn and 751Gln) occurred less frequently among BCC and SCC cases compared with controls (OR = 0.8; 95% CI, 0.6–1.0) for both case groups. In the stratum of subjects who have variant for both XPD polymorphisms, there was a 2-fold increased risk of SCC associated with elevated arsenic (OR = 2.2; 95% CI, 1.0–5.0). The test for interaction between XPD and arsenic in SCC was of borderline significance (p < 0.07, 3 degrees of freedom). Conclusions: Our findings indicate a reduced NMSC risk in relation to XPD Asp312Asn and Lys751Gln variants. Further, these data support the hypothesis that NER polymorphisms may modify the association between NMSC and arsenic