Outdoor Ultrafine Particulate Matter and Risk of Lung Cancer in Southern California.

Rationale: Particulate matter ⩽2.5 µm in aerodynamic diameter (PM2.5) is an established cause of lung cancer, but the association with ultrafine particulate matter (UFP; aerodynamic diameter < 0.1 µm) is unclear. Objectives: To investigate the association between UFP and lung cancer overall and by histologic subtype. Methods: The Los Angeles Ultrafines Study includes 45,012 participants aged ⩾50 years in southern California at enrollment (1995-1996) followed through 2017 for incident lung cancer (n = 1,770). We estimated historical residential ambient UFP number concentrations via land use regression and back extrapolation using PM2.5. In Cox proportional hazards models adjusted for smoking and other confounders, we estimated associations between 10-year lagged UFP (per 10,000 particles/cm3 and quartiles) and lung cancer overall and by major histologic subtype (adenocarcinoma, squamous cell carcinoma, and small cell carcinoma). We also evaluated relationships by smoking status, birth cohort, and historical duration at the residence. Measurements and Main Results: UFP was modestly associated with lung cancer risk overall (hazard ratio [HR], 1.03 [95% confidence interval (CI), 0.99-1.08]). For adenocarcinoma, we observed a positive trend among men; risk was increased in the highest exposure quartile versus the lowest (HR, 1.39 [95% CI, 1.05-1.85]; P for trend = 0.01) and was also increased in continuous models (HR per 10,000 particles/cm3, 1.09 [95% CI, 1.00-1.18]), but no increased risk was apparent among women (P for interaction = 0.03). Adenocarcinoma risk was elevated among men born between 1925 and 1930 (HR, 1.13 [95% CI, 1.02-1.26] per 10,000) but not for other birth cohorts, and was suggestive for men with ⩾10 years of residential duration (HR, 1.11 [95% CI, 0.98-1.26]). We found no consistent associations for women or other histologic subtypes. Conclusions: UFP exposure was modestly associated with lung cancer overall, with stronger associations observed for adenocarcinoma of the lung.

Prediagnostic serum concentrations of per- and polyfluoroalkyl substances and risk of papillary thyroid cancer in the Finnish Maternity Cohort.

Human exposure to per- and polyfluoroalkyl substances (PFAS) occurs globally through contaminated food, dust, and drinking water. Studies of PFAS and thyroid cancer have been limited. We conducted a nested case-control study of prediagnostic serum levels of 19 PFAS and papillary thyroid cancer (400 cases, 400 controls) in the Finnish Maternity Cohort (pregnancies 1986-2010; follow-up through 2016), individually matched on sample year and age. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for log2 transformed and categorical exposures, overall and stratified by calendar period, birth cohort, and median age at diagnosis. We adjusted for other PFAS with Spearman correlation rho = 0.3-0.6. Seven PFAS, including perfluoroctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), N-ethyl-perfluorooctane sulfonamidoacetic acid (EtFOSAA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluorohexane sulfonic acid (PFHxS) were detected in >50% of women. These PFAS were not associated with risk of thyroid cancer, except for PFHxS, which was inversely associated (OR log2 = 0.82, 95% CI: 0.70-0.97). We observed suggestive but imprecise increased risks associated with PFOA, PFOS, and EtFOSAA for those diagnosed at ages <40 years, whereas associations were null or inverse among those diagnosed at 40+ years (P-interaction: .02, .08, .13, respectively). There was little evidence of other interactions. These results show no clear association between PFAS and papillary thyroid cancer risk. Future work would benefit from evaluation of these relationships among those with higher exposure levels and during periods of early development when the thyroid gland may be more susceptible to environmental harms.

Exposure to per- and polyfluoroalkyl substances and breast cancer risk: a systematic review and meta-analysis of epidemiologic studies.

We synthesized the epidemiologic evidence on the associations between per- and polyfluoroalkyl substances (PFAS) exposure and breast cancer risk. Our systematic review and meta-analysis included 18 and 11 articles, respectively, covering studies up to February 2023. The summary relative risks (RRs) estimated by random-effects meta-analyses did not support an association between PFAS and overall breast cancer risk (eg, a natural log (ln)-unit increase in serum/plasma concentrations [ng/mL] for perfluorooctanoate [PFOA] RR = 0.95; 95% CI, 0.77-1.18; perfluorooctane sulfonate [PFOS] RR = 0.98; 95% CI, 0.87-1.11). However, when limiting to studies that assessed exposures prior to a breast cancer diagnosis, we observed a positive association with PFOA (a ln-unit increase, RR = 1.16; 95% CI, 0.96-1.40). We also observed some possible heterogeneous associations by tumor estrogen and progesterone receptor status among postmenopausal breast cancer cases. No meaningful changes were observed after excluding the studies with high risk of bias (Tier 3). Based on the evaluation tool developed by the National Toxicology Program, given the heterogeneity across studies and the variability in timing of exposure measurements, the epidemiologic evidence needed to determine the association between PFAS exposure and breast cancer remains inadequate. Our findings support the need for future studies with improved study designs to determine this association.

Air quality and cancer risk in the All of Us Research Program.

INTRODUCTION: The NIH All of Us Research Program has enrolled over 544,000 participants across the US with unprecedented racial/ethnic diversity, offering opportunities to investigate myriad exposures and diseases. This paper aims to investigate the association between PM2.5 exposure and cancer risks. MATERIALS AND METHODS: This work was performed on data from 409,876 All of Us Research Program participants using the All of Us Researcher Workbench. Cancer case ascertainment was performed using data from electronic health records and the self-reported Personal Medical History questionnaire. PM2.5 exposure was retrieved from NASA's Earth Observing System Data and Information Center and assigned using participants' 3-digit zip code prefixes. Multivariate logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI). Generalized additive models (GAMs) were used to investigate non-linear relationships. RESULTS: A total of 33,387 participants and 46,176 prevalent cancer cases were ascertained from participant EHR data, while 20,297 cases were ascertained from self-reported survey data from 18,133 participants; 9,502 cancer cases were captured in both the EHR and survey data. Average PM2.5 level from 2007 to 2016 was 8.90 µg/m3 (min 2.56, max 15.05). In analysis of cancer cases from EHR, an increased odds for breast cancer (OR 1.17, 95% CI 1.09-1.25), endometrial cancer (OR 1.33, 95% CI 1.09-1.62) and ovarian cancer (OR 1.20, 95% CI 1.01-1.42) in the 4th quartile of exposure compared to the 1st. In GAM, higher PM2.5 concentration was associated with increased odds for blood cancer, bone cancer, brain cancer, breast cancer, colon and rectum cancer, endocrine system cancer, lung cancer, pancreatic cancer, prostate cancer, and thyroid cancer. CONCLUSIONS: We found evidence of an association of PM2.5 with breast, ovarian, and endometrial cancers. There is little to no prior evidence in the literature on the impact of PM2.5 on risk of these cancers, warranting further investigation.

Residential proximity to toxic metal-emitting industrial sites and toenail metal concentrations in a United States-wide prospective cohort.

BACKGROUND: Industrial facilities across the United States (US) release millions of pounds of toxic chemicals, including metals. Exposure to toxic metals has been associated with adverse health outcomes, but there is limited evidence on the association between living near metal-releasing facilities and the body burden of emitted compounds. OBJECTIVE: To investigate the association between residential proximity to toxic metal-emitting industrial facilities and toenail metal concentrations and to evaluate whether associations differed by race. METHODS: In a sample of 1556 non-Hispanic Black (32.5%) and non-Hispanic White (67.5%) women from the Sister Study, we used the US Environmental Protection Agency Toxics Release Inventory to identify metal-emitting facilities within 3, 5, and 10 km of participants' baseline residences. We measured toenail concentrations (µg/g) of arsenic, cadmium, cobalt, chromium, and lead. Using multivariable linear regression, we examined associations between residential proximity to and emissions from metal-emitting facilities and toenail metal concentrations, stratifying by race. We explored modification of race-stratified associations by neighborhood deprivation, using the Area Deprivation Index (ADI). RESULTS: Black participants were more likely to reside within 3 km of chromium-releasing facilities and 5 and 10 km of all observed metal-emitting sites. Living near metal-releasing facilities was not associated with higher toenail metal concentrations overall. Among Black women, higher chromium emissions exposure was associated with higher toenail chromium levels (ßTertile3vs.non-exposed = 2.36 µg/g, 95% CI = 0.63, 4.10). An association with lead was observed among Black women residing in the most deprived areas (≥75th ADI percentile: ß = 3.08 µg/g, 95% CI = 1.46, 4.71). No associations were observed for White participants. CONCLUSIONS: Despite low exposure prevalence, our findings suggest that living near chromium- and lead-releasing facilities, especially at shorter distances, may be associated with higher corresponding toenail metal levels among Black women, particularly those residing in the most disadvantaged areas.

Serum perfluorooctane sulfonate and perfluorooctanoate and risk of postmenopausal breast cancer according to hormone receptor status: An analysis in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

Per- and polyfluoroalkyl substances (PFAS) are highly persistent endocrine-disrupting chemicals that may contribute to breast cancer development; however, epidemiologic evidence is limited. We investigated associations between prediagnostic serum levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) and postmenopausal breast cancer risk, overall and by hormone receptor status, in a nested case-control study of 621 cases and 621 matched controls in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. PFOS and PFOA levels were determined based on serum metabolomic profiling performed using ultraperformance liquid chromatography-tandem mass spectrometry. We used multivariable conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between each PFAS and breast cancer risk, overall, by estrogen receptor (ER) or progesterone receptor (PR) status, and by joint ER/PR status. We found little evidence of association between PFOS or PFOA and breast cancer risk overall. However, in subtype-specific analyses, we observed statistically significant increased risks of ER+, PR+, and ER+/PR+ tumors for the third vs lowest quartile of serum PFOS (ORs [95% CIs] = 1.59 [1.01-2.50], 2.34 [1.29-4.23], and 2.19 [1.21-3.98], respectively) and elevated but nonstatistically significant ORs for the fourth quartile. Conversely, for PFOA, modest positive associations with ER-, PR-, ER+/PR-, and ER-/PR- tumors were generally seen in the upper quartiles. Our findings contribute evidence supporting positive associations between serum PFOS and hormone receptor-positive tumors, and possibly between PFOA and receptor-negative tumors. Future prospective studies incorporating tumor hormone receptor status are needed to better understand the role of PFAS in breast cancer etiology.

Outdoor light at night and risk of endometrial cancer in the NIH-AARP diet and health study.

PURPOSE: Outdoor light at night (LAN) can result in circadian disruption and hormone dysregulation and is a suspected risk factor for some cancers. Our study is the first to evaluate the association between LAN and risk of endometrial cancer, a malignancy with known relationship to circulating estrogen levels. METHODS: We linked enrollment addresses (1996) for 97,677 postmenopausal women in the prospective NIH-AARP cohort to satellite imagery of nighttime radiance to estimate LAN exposure. Multivariable Cox models estimated hazard ratios (HR) and 95% confidence intervals (95% CI) for LAN quintiles and incident endometrial cancer overall (1,669 cases) and endometrioid adenocarcinomas (991 cases) through follow-up (2011). We tested for interaction with established endometrial cancer risk factors. RESULTS: We observed no association for endometrial cancer overall (HRQ1vsQ5 0.92; 95% CI 0.78-1.08; p trend = 0.67) or endometrioid adenocarcinoma (HRQ1vsQ5 1.01; 95% CI 0.82-1.24; p trend = 0.36). Although body mass index and menopause hormone therapy were both associated with risk, there was no evidence of interaction with LAN (p interactions = 0.52 and 0.50, respectively). CONCLUSION: Our study did not find an association between outdoor LAN and endometrial cancer risk, but was limited by the inability to account for individual-level exposure determinants. Future studies should consider approaches to improve characterization of personal exposures to light.

Associations between per- and polyfluoroalkyl substances, liver function, and daily alcohol consumption in a sample of U.S. adults.

BACKGROUND AND AIM: Per- and polyfluoroalkyl substances (PFAS) are ubiquitous in the environment and in the serum of the U.S. POPULATION: We sought to evaluate the association of PFAS independently and jointly with alcohol intake on liver function biomarkers in a sample of the U.S. general population. METHODS: Using data from the National Health and Nutrition Examination Survey (2003-2016; N = 11,794), we examined the five most historically prevalent PFAS with >75% detection rates. We estimated odds ratios (OR) and 95% confidence intervals (CI) for the association between PFAS (quartiles and log-transformed continuous, ng/mL) and high levels (>95th percentile) of liver injury biomarkers using logistic regression models adjusted for key confounders. We evaluated interactions between PFAS and alcohol consumption and sex via stratified analyses and conducted sub-analyses adjusting for daily alcohol intake among those with available drinking history (N = 10,316). RESULT: Serum perfluorooctanoic acid (PFOA) was positively associated with high levels of alanine transferase (ALT) without monotonic trend (ORQ4vsQ1 = 1.45, CI: 0.99-2.12; p-trend = 0.18), and with increased aspartate transaminase when modeled continuously (OR = 1.15, CI: 1.02-1.30; p-trend = 0.03). Perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were both inversely associated with alkaline phosphatase while a trend was evident only for PFHxS (p = 0.02). A non-monotonic inverse association was observed with PFOA (p-trend = 0.10). The highest quartile of PFOS was associated with high total bilirubin (TB; ORQ4vsQ1 = 1.57, CI: 1.01-2.43, p-trend = 0.02). No significant associations were found between any PFAS and γ-glutamyl transpeptidase. We found no associations for perfluorodecanoic acid and perfluorononanoic acid. We observed some suggestive interactions with alcohol intake, particularly among heavy drinkers. CONCLUSION: Consistent with other studies, serum levels of PFOA, PFHxS and PFNA were positively associated with high levels of ALT, and we also observed weak positive associations between some PFAS and TB. Associations observed among heavy drinkers warrant additional evaluation.

Residential proximity to dioxin emissions and risk of breast cancer in the sister study cohort.

Some dioxins are carcinogenic, but few studies have investigated the relationship between ambient polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) and risk of breast cancer. We evaluated associations between proximity-based residential exposure to industrial emissions of PCDD/F and breast cancer risk in a large U.S. cohort. Sister Study participants at enrollment (2003-2009) were followed for incident breast cancer through September 2018. After restricting to participants with ≥10 years of residential history prior to enrollment (n = 35,908), we generated 10-year distance- and toxic equivalency quotient (TEQ)-weighted average emissions indices (AEI [g TEQ/km2]) within 3, 5, or 10 km of participants' residences, overall and by facility type. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between AEI quartiles (vs. zero AEI) and risk of breast cancer [invasive or ductal carcinoma in situ]. There were 2670 incident breast cancer cases over 11 years (median) of follow-up. Breast cancer risk was increased for those in the highest quartile [Q] of AEI exposure within 3 km (HRQ4:1.18, 95% CI: 0.99,1.40, Ptrend = 0.03). The HR was higher for the 10-year AEI at 3 km from municipal solid waste facilities (HR ≥ median.vs.0:1.50, 95% CI: 0.98, 2.29; Ptrend = 0.07). Risk was higher among ever smokers (vs. never smokers) in the top quartile of the 3 km AEI (HRQ4:1.41, 95% CI:1.12,1.77, Ptrend = 0.003; Pinteraction = 0.03) and higher risk for ER negative tumors was suggested (HRQ4:1.47, 95% CI: 0.95, 2.28, Ptrend = 0.07, Pheterogeneity = 0.17). Our findings suggest that residential exposure to PCDD/F emissions may confer an increased risk of breast cancer.

Invited Commentary: Predicting Incidence Rates of Rare Cancers-Adding Epidemiologic and Spatial Contexts.

There are unique challenges to identifying causes of and developing strategies for prevention of rare cancers, driven by the difficulty in estimating incidence, prevalence, and survival due to small case numbers. Using a Poisson modeling approach, Salmerón et al. (Am J Epidemiol. 2022;191(3):487-498) built upon their previous work to estimate incidence rates of rare cancers in Europe using a Bayesian framework, establishing a uniform prior for a measure of variability for country-specific incidence rates. They offer a methodology with potential transferability to other settings with similar cancer surveillance infrastructure. However, the approach does not consider the spatiotemporal correlation of rare cancer case counts and other, potentially more appropriate nonnormal probability distributions. In this commentary, we discuss the implications of future work from cancer epidemiology and spatial epidemiology perspectives. We describe the possibility of developing prediction models tailored to each type of rare cancer; incorporating the spatial heterogeneity in at-risk populations, surveillance coverage, and risk factors in these predictions; and considering a modeling framework with which to address the inherent spatiotemporal components of these data. We note that extension of this methodology to estimate subcountry rates at provincial, state, or smaller geographic levels would be useful but would pose additional statistical challenges.

Emissions of dioxins and dioxin-like compounds and incidence of hepatocellular carcinoma in the United States.

Ambient dioxin exposure from industrial sources, excluding exposures from occupations and accidental releases/contamination, may be associated with risk of developing hepatocellular carcinoma (HCC). The objective of this study was to examine the association between county-level ambient dioxin air emissions from industrial sources and HCC risk in the US. We obtained information on 90,359 incident HCC cases diagnosed between 2000 and 2016 from population-based cancer registries across the US in the Surveillance, Epidemiology, and End Results (SEER) database. Dioxin emissions from 1987 to 2007 from a nationwide spatial database of historical dioxin-emitting facilities were linked to the SEER county of residence at diagnosis using a geographic information system (GIS). Poisson regression with robust variance estimation was used to calculate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for the association between county-level dioxin emissions and HCC rates adjusting for individual-level age at diagnosis, sex, race/ethnicity, year of diagnosis, SEER registry, and county-level information on health conditions, lifestyle factors, and socioeconomic status. There was no association between dioxin emissions based on the number of dioxin-emitting facilities within a county or average annual emissions within a county and HCC risk. In analyses by facility type, there were positive associations between county-level dioxin emissions from coal-fired power plants (adjusted IRR 1.09, 95% CI 1.01-1.17), but not with the number of these facilities. Similarly, positive associations for industrial boilers and sewage sludge incinerators were evident, but not consistent across both exposure metrics. Future research should incorporate individual-level data to further explore the findings suggested by these ecologic analyses.

Associations between artificial light at night and risk for thyroid cancer: A large US cohort study.

BACKGROUND: Light at night (LAN) inhibits nighttime secretion of melatonin and may cause circadian disruption, which may be a risk factor for cancer. Recent studies have linked high LAN exposure with elevated breast cancer risk. Given that breast cancer may share a common hormone-dependent etiology with thyroid cancer and that circadian rhythms play a role in regulating thyroid function, the authors hypothesized that exposure to LAN is positively associated with thyroid cancer incidence. METHODS: This study examined the association between LAN and thyroid cancer incidence in the National Institutes of Health-American Association of Retired Persons Diet and Health Study. LAN exposure was estimated from satellite data and was linked to residential addresses at the baseline. Incident thyroid cancer cases were ascertained via linkage to state cancer registries. Cox regression was used to determine the relationship between LAN and thyroid cancer risk, with adjustments made for sociodemographic, lifestyle, and other environmental factors. RESULTS: Among 464,371 participants, a positive association was found between LAN and thyroid cancer risk. Specifically, in comparison with the lowest quintile of LAN, the highest quintile was associated with a 55% increase in risk (hazard ratio [HR], 1.55; 95% confidence interval [CI], 1.18-2.02). The association was primarily driven by papillary thyroid cancer and was stronger in women (HR, 1.81; 95% CI, 1.26-2.60) than men (HR, 1.29; 95% CI, 0.86-1.94). In women, the association was stronger for localized cancer, whereas in men, the association was stronger for a more advanced stage. Results were consistent across different tumor sizes. CONCLUSIONS: LAN was positively associated with thyroid cancer risk. Future studies are needed to confirm this association and identify underlying biological mechanisms.

Exposure to artificial light at night and risk of cancer: where do we go from here?

Despite experimental and mechanistic data suggesting circadian disruption's role in carcinogenesis, mixed findings from epidemiological investigations of artificial light at night and cancer risk in the general population are difficult to interpret due to exposure assessment limitations. It will be important for future studies to assess and validate individual-level exposures, ideally over the lifetime.

Residential exposure to carbamate, organophosphate, and pyrethroid insecticides in house dust and risk of childhood acute lymphoblastic leukemia.

BACKGROUND: Self-reported residential use of pesticides has consistently been associated with increased risk of childhood leukemia. However, these studies were limited in their ability to identify specific insecticide active ingredients that were associated with risk. OBJECTIVE: We used household carpet dust measurements of 20 insecticides (two carbamate, 10 organophosphate, two organochlorine, and six pyrethroid) as indicators of exposure and evaluated associations with the risk of childhood acute lymphoblastic leukemia (ALL). METHODS: We conducted a population-based case-control study of 252 ALL cases diagnosed from 1999 to 2007 and 306 birth certificate controls from 35 counties in Central and Northern California. Carpet dust was collected at a second interview (2001-2007) for cases who had not moved since diagnosis (comparable reference date for controls) using a specialized vacuum cleaner in the room where the child spent most of their time or from the household vacuum. Insecticides were categorized as detected (yes/no), or as tertiles or quartiles of their distributions among controls. We calculated odds ratios (OR) and 95% confidence intervals (CI) using unconditional logistic regression adjusting for demographic characteristics, interview year, and season of dust collection. RESULTS: Permethrin, chlorpyrifos, diazinon, and carbaryl were the most frequently detected insecticide active ingredients. When we compared the highest quartile to the lowest or to non-detections, there was no association with ALL for permethrin (OR Q4 vs. Q1 = 0.81; 95% CI 0.50-1.31), carbaryl (OR Q4 vs. non-detects = 0.61, 95% CI 0.34-1.08) or chlorpyrifos (OR Q4 vs. Q1 = 0.60; 95% CI 0.36-1.00). The highest quartile of diazinon concentration was inversely associated with risk in the single pesticide model but without a monotonic exposure-response (p-trend = 0.14). After adjusting for other common insecticides, the OR was not significant (OR Q4 vs. Q1 = 0.58; 95% CI 0.33-1.05). None of the other insecticides were associated with risk. CONCLUSION: Our results should be interpreted within the limitations of the case-control study design including the use of a single post-diagnosis dust sample and restriction to residentially stable participants, which may have resulted in selection bias. Although difficult to implement, additional studies with assessment of exposure to insecticide active and non-active ingredients are necessary to elucidate the role of these common exposures in childhood leukemia risk.

Evaluation of a commercial database to estimate residence histories in the los angeles ultrafines study.

BACKGROUND: Commercial databases can be used to identify participant addresses over time, but their quality and impact on environmental exposure assessment is uncertain. OBJECTIVE: To evaluate the performance of a commercial database to find residences and estimate environmental exposures for study participants. METHODS: We searched LexisNexis® for participant addresses in the Los Angeles Ultrafines Study, a prospective cohort of men and women aged 50-71 years. At enrollment (1995-1996) and follow-up (2004-2005), we evaluated attainment (address found for the corresponding time period) and match rates to survey addresses by participant characteristics. We compared geographically-referenced predictors and estimates of ultrafine particulate matter (UFP) exposure from a land use regression model using LexisNexis and survey addresses at enrollment. RESULTS: LexisNexis identified an address for 69% of participants at enrollment (N = 50,320) and 95% of participants at follow-up (N = 24,432). Attainment rate at enrollment modestly differed (≥5%) by age, smoking status, education, and residential mobility between surveys. The match rate at both survey periods was high (82-86%) and similar across characteristics. When using LexisNexis versus survey addresses, correlations were high for continuous values of UFP exposure and its predictors (rho = 0.86-0.92). SIGNIFICANCE: Time period and population characteristics influenced the attainment of addresses from a commercial database, but accuracy and subsequent estimation of specific air pollution exposures were high in our older study population.

Acute ambient air pollution exposure and placental Doppler results in the NICHD fetal growth studies - Singleton cohort.

BACKGROUND: Increased placental vascular resistance is a proposed mechanism by which air pollution exposure during pregnancy lowers birth weight and increases pregnancy-induced hypertensive disorders. OBJECTIVE: To examine the impact of acute air pollution exposure during pregnancy on uterine and umbilical artery Doppler indicators of placental vascular resistance. METHODS: After a first ultrasound to confirm gestational age, 2562 pregnant women recruited in 12 clinics throughout the United States underwent up to five standardized ultrasounds with Doppler measurements. Exposures to 11 air pollutants were estimated for the hour of ultrasound and each of the 2 h prior to ultrasound at the clinics using the National Air Quality Forecast Capability reanalysis products. We used mixed logistic regression to study the longitudinal odds ratio (OR) of any, uni- or bi-lateral systolic and diastolic uterine artery notching compared to no notching and the longitudinal OR of abnormal end diastolic flow of the umbilical artery compared to forward flow. Uterine and umbilical artery resistance indexes were studied using linear mixed models. RESULTS: Each inter-quartile range (IQR) increase of particulate matter < 2.5 µm, nitrate, ammonium, primary organic matter (POM) and nitrogen dioxide during the hour of ultrasound was associated with a decreased risk of unilateral systolic notch and with increased resistance index of the left uterine artery. For the umbilical artery, each IQR increase in ozone was associated with decreased resistance index (b: -0.26, 95 % CI: -0.52, -0.01) and with a decreased risk of abnormal end diastolic flow (OR: 0.36, 95 % CI: 0.14, 0.94); while each IQR increase of elemental carbon and POM was associated with increased risk of abnormal end diastolic flow (OR: 1.47, 95 % CI: 1.02, 2.13 and OR: 1.67, 95 % CI: 1.17, 2.39, respectively). DISCUSSION: Our results suggest acute air pollution exposure may influence placental vascular resistance.

sparrpowR: a flexible R package to estimate statistical power to identify spatial clustering of two groups and its application.

BACKGROUND: Cancer epidemiology studies require sufficient power to assess spatial relationships between exposures and cancer incidence accurately. However, methods for power calculations of spatial statistics are complicated and underdeveloped, and therefore underutilized by investigators. The spatial relative risk function, a cluster detection technique that detects spatial clusters of point-level data for two groups (e.g., cancer cases and controls, two exposure groups), is a commonly used spatial statistic but does not have a readily available power calculation for study design. RESULTS: We developed sparrpowR as an open-source R package to estimate the statistical power of the spatial relative risk function. sparrpowR generates simulated data applying user-defined parameters (e.g., sample size, locations) to detect spatial clusters with high statistical power. We present applications of sparrpowR that perform a power calculation for a study designed to detect a spatial cluster of incident cancer in relation to a point source of numerous environmental emissions. The conducted power calculations demonstrate the functionality and utility of sparrpowR to calculate the local power for spatial cluster detection. CONCLUSIONS: sparrpowR improves the current capacity of investigators to calculate the statistical power of spatial clusters, which assists in designing more efficient studies. This newly developed R package addresses a critically underdeveloped gap in cancer epidemiology by estimating statistical power for a common spatial cluster detection technique.

Mediterranean Diet and the Association Between Air Pollution and Cardiovascular Disease Mortality Risk.

BACKGROUND: Recent experimental evidence suggests that nutritional supplementation can blunt adverse cardiopulmonary effects induced by acute air pollution exposure. However, whether usual individual dietary patterns can modify the association between long-term air pollution exposure and health outcomes has not been previously investigated. We assessed, in a large cohort with detailed diet information at the individual level, whether a Mediterranean diet modifies the association between long-term exposure to ambient air pollution and cardiovascular disease mortality risk. METHODS: The National Institutes of Health-American Association for Retired Persons Diet and Health Study, a prospective cohort (N=548 845) across 6 states and 2 cities in the United States and with a follow-up period of 17 years (1995-2011), was linked to estimates of annual average exposures to fine particulate matter and nitrogen dioxide at the residential census-tract level. The alternative Mediterranean Diet Index, which uses a 9-point scale to assess conformity with a Mediterranean-style diet, was constructed for each participant from information in cohort baseline dietary questionnaires. We evaluated mortality risks for cardiovascular disease, ischemic heart disease, cerebrovascular disease, or cardiac arrest associated with long-term air pollution exposure. Effect modification of the associations between exposure and the mortality outcomes by alternative Mediterranean Diet Index was examined via interaction terms. RESULTS: For fine particulate matter, we observed elevated and significant associations with cardiovascular disease (hazard ratio [HR] per 10 µg/m3, 1.13; 95% CI, 1.08-1.18), ischemic heart disease (HR, 1.16; 95% CI, 1.10-1.23), and cerebrovascular disease (HR, 1.15; 95% CI, 1.03-1.28). For nitrogen dioxide, we found significant associations with cardiovascular disease (HR per 10 ppb, 1.06; 95% CI, 1.04-1.08) and ischemic heart disease (HR, 1.08; 95% CI, 1.05-1.11). Analyses indicated that Mediterranean diet modified these relationships, as those with a higher alternative Mediterranean Diet Index score had significantly lower rates of cardiovascular disease mortality associated with long-term air pollution exposure ( P-interaction<0.05). CONCLUSIONS: A Mediterranean diet reduced cardiovascular disease mortality risk related to long-term exposure to air pollutants in a large prospective US cohort. Increased consumption of foods rich in antioxidant compounds may aid in reducing the considerable disease burden associated with ambient air pollution.

Outdoor air pollution and terminal duct lobular involution of the normal breast.

BACKGROUND: Exposure to certain outdoor air pollutants may be associated with a higher risk of breast cancer, though potential underlying mechanisms are poorly understood. We examined whether outdoor air pollution was associated with involution of terminal duct lobular units (TDLUs), the histologic site where most cancers arise and an intermediate marker of breast cancer risk. METHODS: Pathologist-enumerated TDLUs were assessed in H&E (hematoxylin and eosin)-stained breast tissue sections from 1904 US women ages 18-75 who donated to the Susan G. Komen Tissue Bank (2009-2012). The 2009 annual fine particulate matter < 2.5 µm in diameter (PM2.5) total mass (µg/m3) at each woman's residential address was estimated from the Environmental Protection Agency's Downscaler Model combining Community Multiscale Air Quality (CMAQ) System modeling with air quality monitoring data. We secondarily considered CMAQ-modeled components of PM2.5 and gaseous pollutants. We used K-means clustering to identify groups of individuals with similar levels of PM2.5 components, selecting groups via cluster stability analysis. Relative rates (RRs) and 95% confidence intervals (95% CIs) for the association between air pollutants and TDLU counts were estimated from a zero-inflated negative binomial regression model adjusted for potential confounders. RESULTS: PM2.5 total mass was associated with higher TDLU counts among all women (interquartile range (IQR) increase, RR = 1.06; 95% CI: 1.01-1.11). This association was evident among both premenopausal and postmenopausal women (premenopausal RR = 1.05, 95% CI: 1.00-1.11; postmenopausal RR = 1.11, 95% CI: 1.00-1.23). We identified 3 groups corresponding to clusters that varied geographically and roughly represented high, medium, and low levels of PM2.5 components relative to population mean levels. Compared to the cluster with low levels, the clusters with both high (RR = 1.74; 95% CI: 1.08-2.80) and medium (RR = 1.82; 95% CI: 1.13-2.93) levels were associated with higher TDLU counts; although not significantly different, the magnitude of the associations was stronger among postmenopausal women. CONCLUSIONS: Higher PM2.5 levels were associated with reduced TDLU involution as measured by TDLU counts. Air pollution exposure may influence the histologic characteristics of normal tissue which could in turn affect breast cancer risk.

Outdoor light at night and postmenopausal breast cancer risk in the NIH-AARP diet and health study.

Circadian disruption may play a role in breast carcinogenesis. Previous studies reported relationships between outdoor light at night (LAN) and the breast cancer risk, but their findings are mixed. There is also a need to examine LAN and breast cancer incidence according to different individual and environmental characteristics to identify subpopulations at greater risk associated with LAN exposure. We studied residential outdoor LAN estimated from satellite imagery at baseline (1996) in relation to postmenopausal breast cancer incidence over ~16 years of follow-up in 186 981 postmenopausal women including 12 318 incident postmenopausal breast cancer cases in the NIH-AARP Diet and Health Study. We used Cox proportional hazards models to estimate hazard ratios (HR) and two-sided 95% confidence intervals (CI) of the relationship between quintiles of LAN and postmenopausal breast cancer risk, overall and by hormone receptor status and cancer stage. We found that when compared to women in the lowest quintile of baseline LAN, those in the highest quintile had a 10% increase in postmenopausal breast cancer risk (HR (95% CI), 1.10 (1.02, 1.18), P-trend, .002). The association appeared to be stronger for estrogen receptor (ER) positive breast cancer (1.12 [1.02, 1.24], .007) than for ER-negative cancer (1.07 [0.85, 1.34], .66). Our findings also suggested that the relationship between LAN and breast cancer risk may differ by individual characteristics, such as smoking, alcohol drinking, sleep duration and BMI, and neighborhood environment. In conclusion, our study suggests that higher outdoor LAN exposure may be a risk factor for postmenopausal breast cancer.