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BACKGROUND:Toxic metals show evidence of carcinogenic and estrogenic properties. However, little is known about the relationship between airborne metals and breast cancer. We evaluated the risk of breast cancer in relation to exposure to toxic metallic substances in air, individually and combined, in a US-wide cohort. METHODS:Sister Study participants (n = 50,884), breast cancer–free women who had a sister with breast cancer were recruited, from 2003 to 2009. The 2005 Environmental Protection Agency National Air Toxic Assessment’s census-tract estimates of metal concentrations in air (antimony, arsenic, cadmium, chromium, cobalt, lead, manganese, mercury, nickel, and selenium) were matched to participants’ enrollment residence. We used Cox regression to estimate the association between quintiles of individual metals and breast cancer incidence and weighted quantile sum regression to model the association between the metal mixture and breast cancer. RESULTS:A total of 2,587 breast cancer cases were diagnosed during follow-up (mean = 7.4 years). In individual chemical analyses comparing the highest to lowest quintiles, postmenopausal breast cancer risk was elevated for mercury (hazard ratio [HR] = 1.3, 95% confidence interval [CI], 1.1, 1.5), cadmium (HR = 1.1, 95% CI, 0.96, 1.3), and lead (HR = 1.1, 95% CI, 0.98, 1.3). The weighted quantile sum index was associated with postmenopausal breast cancer (odds ratio [OR] = 1.1, 95% CI, 1.0, 1.1). Consistent with the individual chemical analysis, the most highly weighted chemicals for predicting postmenopausal breast cancer risk were lead, cadmium, and mercury. Results were attenuated for overall breast cancer. CONCLUSIONS:Higher levels of some airborne metals, specifically mercury, cadmium, and lead, were associated with a higher risk of postmenopausal breast cancer.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous organic compounds associated with chronic disease in epidemiologic studies, though the contribution of PAH exposure on fatal outcomes in the U.S. is largely unknown. We investigated urinary hydroxylated PAH metabolites (OH-PAHs) with all-cause and cause-specific mortality in a representative sample of the U.S. population. Study participants were ≥20 years old from the National Health and Nutrition Examination Survey 2001-2014. Concentrations (nmol/L) of eight OH-PAHs from four parent PAHs (naphthalene, fluorene, phenanthrene, pyrene) were measured in spot urine samples at examination. We identified all-cause, cancer-specific, and cardiovascular-specific deaths through 2015 using the National Death Index. We used Cox proportional hazards regression to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between ΣOH-PAHs and mortality endpoints. We assessed potential heterogeneity by age, gender, smoking status, poverty, and race/ethnicity. Additionally, we examined the overall mixture effect using quantile g-computation. In 9,739 eligible participants, there were 934 all-cause deaths, 159 cancer-specific deaths, and 108 cardiovascular-specific deaths (median 6.75 years follow-up). A log10 increase in ΣOH-PAHs was associated with higher all-cause mortality (HRadj = 1.39 [95%CI: 1.21, 1.61]), and possibly cancer-specific mortality (HRadj = 1.15 [95%CI: 0.79, 1.69]), and cardiovascular-specific mortality (HRadj = 1.49 [95%CI: 0.94, 2.33]). We observed substantial effect modification by age, smoking status, gender, and race/ethnicity across mortality endpoints. Risk of cardiovascular mortality was higher for non-Hispanic blacks and those in poverty, indicating potential disparities. Quantile g-computation joint associations for a simultaneous quartile increase in OH-PAHs were HRadj = 1.15 [95%CI: 1.02, 1.31], HRadj = 1.41 [95%CI: 1.05, 1.90], and HRadj = 0.98 [95%CI: 0.66, 1.47] for all-cause, cancer-specific, and cardiovascular-specific mortalities, respectively. Our results support a role for total PAH exposure in all-cause and cause-specific mortality in the U.S. population.

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 (PM 2.5 ) total mass (μg/m 3 ) 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 PM 2.5 and gaseous pollutants. We used K -means clustering to identify groups of individuals with similar levels of PM 2.5 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 PM 2.5 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 PM 2.5 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 PM 2.5 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.

Iron status is often assessed in epidemiologic studies, and toenails offer a convenient alternative to serum because of ease of collection, transport, and storage, and the potential to reflect a longer exposure window. Very few studies have examined the correlation between serum and toenail levels for trace metals. Our aim was to compare iron measures using serum and toenails on both a cross-sectional and longitudinal basis. Using a subset of the US-wide prospective Sister Study cohort, we compared toenail iron measures to serum concentrations for iron, ferritin and percent transferrin saturation. Among 146 women who donated both blood and toenails at baseline, a subsample (59%, n = 86) provided specimens about 8 years later. Cross-sectional analyses included nonparametric Spearman’s rank correlations between toenail and serum biomarker levels. We assessed within-woman maintenance of rank across time for the toenail and serum measures and fit mixed effects models to measure change across time in relation to change in menopause status. Spearman correlations at baseline (follow-up) were 0.08 (0.09) for serum iron, 0.08 (0.07) for transferrin saturation, and − 0.09 (− 0.17) for ferritin. The within-woman Spearman correlation for toenail iron between the two time points was higher (0.47, 95% CI 0.30, 0.64) than for serum iron (0.30, 95% CI 0.09, 0.51) and transferrin saturation (0.34, 95% CI 0.15, 0.54), but lower than that for ferritin (0.58, 95% CI 0.43, 0.73). Serum ferritin increased over time while nail iron decreased over time for women who experienced menopause during the 8-years interval. Based on cross-sectional and repeated assessments, our evidence does not support an association between serum biomarkers and toenail iron levels. Toenail iron concentrations did appear to be moderately stable over time but cannot be taken as a proxy for serum iron biomarkers and they may reflect physiologically distinct fates for iron.

More than 73 million people in the United States live within 3 mi (5 km) of a Superfund site, which can be sources of uncontrolled hazardous waste. These sites tend to be in areas of lower socioeconomic status or with higher proportions of people of color. Many Superfund sites release metals into different environmental media, making the sites plausible sources of exposure for nearby communities. We aimed to evaluate associations between residential proximity to metal-containing Superfund sites and toenail metal biomarker concentrations, with consideration of how these associations varied by race to assess the potential for unequal burden of exposure. Non-Hispanic Black women had a slightly higher residential density of all types of metal-containing Superfund sites than non-Hispanic White women. Median toenail concentrations of arsenic and cadmium were higher in non-Hispanic White women, whereas the median concentration of antimony was higher in non-Hispanic Black women Overall, we observed positive associations between the IDW score for Superfund sites containing antimony (87.4%, 95% CI: 20.5, 191) and leadin relation to respective toenail levels.

Purpose Adult physical activity is associated with reduced breast cancer risk, but few studies have evaluated activity before adulthood. Early life may be an important period because of rapid breast development and hormonal changes. This study contributes new information by examining childhood (ages 5–12) and teenage (ages 13–19) activity separately and overall. Methods The Sister Study is a cohort of 50,884 women aged 35–74. Women reported age 5–19 sports/exercise activities and age 10 and 16 unstructured activities. Both hours and MET-hours of activity were considered in association with breast cancer overall, by ER status, and by menopausal status. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with Cox proportional hazards models. Results 2416 cases were diagnosed during follow-up (mean = 6.4 years). Participation in 7+ hours (vs <1 h) per week of sports/exercise during ages 5–19 was associated with reduced breast cancer risk (HR = 0.75; 95% CI 0.57–0.99). 7+ hours (vs <1 h) per week of unstructured physical activity at age 16, but not age 10, was inversely associated with breast cancer (HR = 0.81; 95% CI 0.70–0.95). Associations were more pronounced for ER+ tumors, especially for activity during the childhood (ages 5–12) period. Due to low correlation between childhood/teenage and adulthood activity in this study ( r  = 0.1), it is unlikely that recent activity explains our results. Conclusions Findings from this large cohort indicate higher levels of physical activity during ages 5–19 are inversely associated with breast cancer risk, supporting early life as a window of susceptibility for breast cancer development.

BACKGROUND:To date, epidemiologic studies have not strongly supported an association between pesticide exposure and breast cancer. However, few previous studies had the ability to assess specific time periods of exposure. Studies that relied on adult serum levels of metabolites of organochlorine pesticides may not accurately reflect exposure during developmental periods. Furthermore, exposure assessment often occurred after diagnosis and key tumor characteristics, such as hormone receptor status, have rarely been available to evaluate tumor subtype-specific associations. We examined the association between pesticide exposure during childhood and adolescence and breast cancer risk in the prospective Sister Study cohort (N = 50,884 women) to assess this relation by tumor subtype. METHODS:During an average 5-year follow-up, 2,134 incident invasive and in situ breast cancer diagnoses were identified. Residential and farm exposure to pesticides were self-reported at study enrollment during standardized interviews. Multivariable hazard ratios and 95% confidence intervals for breast cancer risk were calculated with Cox proportional hazards regression. RESULTS:HRs were near null for the association between childhood/adolescent pesticide exposure and breast cancer risk overall or among ER+/PR+ invasive tumors. However, among women who were ages 0–18 before the ban of dichlordiphenyltrichloroethane in the US, exposure to fogger trucks or planes was associated with a hazard ratio = 1.3 for premenopausal breast cancer (95% confidence interval0.92, 1.7). CONCLUSION:These findings do not support an overall association between childhood and adolescent pesticide exposure and breast cancer risk. However, modest increases in breast cancer risk were associated with acute events in a subgroup of young women.

Barrett's esophagus (BE) is the key precursor lesion of esophageal adenocarcinoma, a lethal cancer that has increased rapidly in westernized countries over the past four decades. Dietary sugar intake has also been increasing over time, and may be associated with these tumors by promoting hyperinsulinemia. The study goal was to examine multiple measures of sugar/starches intake in association with BE. This pooled analysis included 472 BE cases and 492 controls from two similarly conducted case-control studies in the United States. Dietary intake data, collected by study-specific food frequency questionnaires, were harmonized across studies by linking with the University of Minnesota Nutrient Database, and pooled based on study-specific quartiles. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for age, sex, race, total energy intake, study indicator, body mass index, frequency of gastro-esophageal reflux, and fruit/vegetable intake. In both studies, intake of sucrose (cases vs. controls, g/day: 36.07 vs. 33.51; 36.80 vs. 35.06, respectively) and added sugar (46.15 vs. 41.01; 44.18 vs. 40.68, respectively) were higher in cases than controls. BE risk was increased 79% and 71%, respectively, for associations comparing the fourth to the first quartile of intake of sucrose (ORQ4VS.Q1 = 1.79, 95% CI = 1.07-3.02, Ptrend= 0.01) and added sugar (ORQ4VS.Q1 = 1.71, 95% CI = 1.05-2.80, Ptrend = 0.15). Intake of sweetened desserts/beverages was associated with 71% increase in BE risk (ORQ4VS.QI = 1.71, 95% CI = 1.07-2.73, Ptrend = 0.04). Limiting dietary intake of foods and beverages that are high in added sugar, especially refined table sugar, may reduce the risk of developing BE.

Purpose. Millions of tons of ambient air toxics are released in the United States (US) each year. Understanding their impact on health outcomes is significant. Results from studies examining the association between air toxics and breast cancer have been inconsistent and no studies have examined the association between air toxics and shorter telomere length, a biomarker of aging, in a non-occupational setting. It is unknown whether body mass index (BMI) or physical activity modify these associations. Methods. Using census tract concentration estimates from the 2005 National Air Toxics Assessment, 29 non-metallic air toxics were examined. Associations between individual air toxics and breast cancer were estimated with Cox regression using 49,718 Sister Study women. Single-pollutant associations for telomere length were examined with linear regression using a random subcohort of 731 women. Effect-measure modification by BMI and physical activity was examined. Classification and regression trees (CART) were used to explore combinations of air toxics and covariates related to these outcomes. Results. With follow-up through September 2016, 2,975 ductal carcinoma in situ or invasive breast cancers were diagnosed (average follow-up time=8.4 years). The average telomere length, measured as the T/S ratio, in the subcohort was 1.24. Methylene chloride was consistently associated with increased breast cancer risk across analyses (e.g. overall breast cancer hazard ratio (HR)quintile4vs1=1.21; 95% confidence interval (CI): 1.07, 1.38). Associations for overall or estrogen receptor-positive (ER+) breast cancer were also observed for acrylamide, polycyclic organic matter, propylene dichloride, and styrene. BMI modified the association for six air toxics. Benzidine, 1,4-dioxane, carbon tetrachloride, chloroprene, ethylene dibromide, and propylene dichloride were associated with shorter telomere length. Combinations identified using CART included: age, methylene chloride, BMI, ethylidene dichloride, propylene dichloride, ethylene dibromide, and styrene in association with breast cancer; and age, BMI, physical activity, ethylene oxide, acrylonitrile, ethylidene dichloride, propylene dichloride, and styrene in association with telomere length. Conclusions. Several air toxics were associated with an increased overall and ER+ breast cancer risk. Some air toxic-breast cancer associations were stronger among overweight/obese women. Benzidine and 1,4-dioxane, and perhaps carbon tetrachloride, chloroprene, ethylene dibromide, and propylene dichloride were associated with shorter telomere length.

Seasonal vertical migration of large lipid-rich copepods is often described as a mass descent of animals when primary production ceases, with important implications for mesopelagic food webs and global carbon sequestration. This view ignores the existence of surface-resident individuals, but here we show that non-migrants can form a substantial part of the populations of polar migrant species. In the Central Arctic Ocean, the biomass-dominant Calanus hyperboreus was evenly distributed throughout the water column from November 2019 to March 2020, with ~20% of subadults and adult females remaining in the upper 200 m and ~41% migrating to 1000–2000 m. These vertical positions aligned with differences in the copepods’ cholesterol content, which can enhance the tissue density at higher temperatures. Gonad development and the vertical distribution of their offspring indicate that both non-migrant and migrant females contribute to the population recruitment. We reinterpret copepod seasonal migration as a bet-hedging strategy that balances nutritional benefits near the surface with survival benefits at depth, and thereby contributes to the species’ resilience under climatic change.