Explore the vast range of titles available.

Particulate matter (PM) is a complex mixture. Geographic variations in PM may explain the lack of consistent associations with breast cancer. We aimed to evaluate the relationship between air pollution, PM components, and breast cancer risk in a United States-wide prospective cohort. We estimated annual average ambient residential levels of particulate matter and in aerodynamic diameter ( and , respectively) and nitrogen dioxide ( ) using land-use regression for 47,433 Sister Study participants (breast cancer-free women with a sister with breast cancer) living in the contiguous United States. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk associated with an interquartile range (IQR) increase in pollutants. Predictive -means were used to assign participants to clusters derived from component profiles to evaluate the impact of heterogeneity in the mixture. For , we investigated effect measure modification by component cluster membership and by geographic region without regard to air pollution mixture. During follow-up ( ), 2,225 invasive and 623 ductal carcinoma (DCIS) cases were identified. and were associated with breast cancer overall [ (95% CI:0.99, 1.11) and 1.06 (95% CI:1.02, 1.11), respectively] and with DCIS but not with invasive cancer. Invasive breast cancer was associated with only in the Western United States [ (95% CI:1.02, 1.27)] and only in the Southern United States [ (95% CI:1.01, 1.33)]. was associated with a higher risk of invasive breast cancer among two of seven identified composition-based clusters. A higher risk was observed [ (95% CI: 0.97, 1.60)] in a California-based cluster characterized by low S and high Na and nitrate ( ) fractions and for another Western United States cluster [ (95% CI: 0.90, 2.85)], characterized by high fractions of Si, Ca, K, and Al. Air pollution measures were related to both invasive breast cancer and DCIS within certain geographic regions and PM component clusters. https://doi.org/10.1289/EHP5131.

Background Earlier age at menarche is an established risk factor for breast cancer. While age at menarche has been fairly stable over the past half-century, age at breast development (thelarche) has continued to decrease. Recently, earlier age at thelarche and a longer time between thelarche and menarche (pubertal tempo) were shown to be associated with increased breast cancer risk. Our objective was to examine how breast cancer risk was associated with pubertal timing and tempo in a prospective US cohort. Methods Women ages 35–74 years without a history of breast cancer, but who had a sister previously diagnosed with breast cancer, were enrolled in the Sister Study from 2003 to 2009 ( N  = 50,884). At enrollment, participants reported their ages at thelarche and menarche. Pubertal tempo was age at menarche minus age at thelarche. We estimated adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for each pubertal milestone and risk of breast cancer (invasive or ductal carcinoma in situ) using Cox proportional hazards regression. We examined whether associations between age at thelarche and breast cancer risk were modified by birth cohort, race/ethnicity, weight at age 10, and extent of breast cancer family history, as characterized by a Bayesian score based on first-degree family structure. Results During follow-up (mean = 9.3 years), 3295 eligible women were diagnosed with breast cancer. Early ages at thelarche (HR = 1.23, 95% CI 1.03–1.46 for < 10 vs. 12–13 years) and menarche (HR = 1.10, 95% CI 1.01–1.20 for < 12 vs. 12–13 years) were positively associated with breast cancer risk. Pubertal tempo was not associated with breast cancer risk (HR = 0.99, 95% CI 0.97–1.02 per 1-year longer tempo). When considering early thelarche (< 10 years) and early menarche (< 12 years) jointly, women with both had a 30% greater risk of breast cancer compared with women with neither risk factor (95% CI 1.07–1.57). The association between age at thelarche and breast cancer risk did not significantly vary by birth cohort, race/ethnicity, childhood weight, or Bayesian family history score. Conclusions Earlier ages at thelarche and menarche may enhance susceptibility to breast carcinogenesis. Age at thelarche is an important risk factor to consider given secular trends towards earlier development.

Anorexia and bulimia nervosa may have long-term effects on overall and reproductive health. We studied predictors of self-reported eating disorders and associations with later health events. We estimated odds ratios (ORs) for these associations in 47,759 participants from the Sister Study. Two percent (n = 967) of participants reported a history of an eating disorder. Risk factors included being non-Hispanic white, having well-educated parents, recent birth cohort (OR = 2.16, 95% confidence interval [CI]: 2.01-2.32 per decade), and having a sister with an eating disorder (OR = 3.68, CI: 1.92-7.02). As adults, women who had experienced eating disorders were more likely to smoke, to be underweight, to have had depression, to have had a later first birth, to have experienced bleeding or nausea during pregnancy, or to have had a miscarriage or induced abortion. In this descriptive analysis, we identified predictors of and possible long-term health consequences of eating disorders. Eating disorders may have become more common over time. Interventions should focus on prevention and mitigation of long-term adverse health effects.

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.

The Sister Study was designed to address gaps in the study of environment and breast cancer by taking advantage of more frequent breast cancer diagnoses among women with a sister history of breast cancer and the presumed enrichment of shared environmental and genetic exposures. The Sister Study sought a large cohort of women never diagnosed with breast cancer but who had a sister (full or half) diagnosed with breast cancer. A multifaceted national effort employed novel strategies to recruit a diverse cohort, and collected biological and environmental samples and extensive data on potential breast cancer risk factors. The Sister Study enrolled 50,884 U.S. and Puerto Rican women 35-74y of age (median 56 y). Although the majority were non-Hispanic white, well educated, and economically well off, substantial numbers of harder-to-recruit women also enrolled (race/ethnicity other than non-Hispanic white: 16%; no college degree: 35%; household income <$50,000: 26%). Although all had a biologic sister with breast cancer, 16.5% had average or lower risk of breast cancer according to the Breast Cancer Risk Assessment Tool (Gail score). Most were postmenopausal (66%), parous with a first full-term pregnancy <30y of age (79%), never-smokers (56%) with body mass indexes (BMIs) of <29.9 kg/m (70%). Few (5%) reported any cancer prior to enrollment. The Sister Study is a unique cohort designed to efficiently study environmental and genetic risk factors for breast cancer. Extensive exposure data over the life-course and baseline specimens provide important opportunities for studying breast cancer and other health outcomes in women. Collaborations are welcome. https://doi.org/10.1289/EHP1923.

The 2010 disaster led to the largest ever marine oil spill. Individuals who worked on the spill were exposed to toxicants and stressors that could lead to adverse effects. The GuLF STUDY was designed to investigate relationships between oil spill exposures and multiple potential physical and mental health effects. Participants were recruited by telephone from lists of individuals who worked on the oil spill response and clean-up or received safety training. Enrollment interviews between 2011 and 2013 collected information about spill-related activities, demographics, lifestyle, and health. Exposure measurements taken during the oil spill were used with questionnaire responses to characterize oil exposures of participants. Participants from Gulf states completed a home visit in which biological and environmental samples, anthropometric and clinical measurements, and additional health and lifestyle information were collected. Participants are being followed for changes in health status. Thirty-two thousand six hundred eight individuals enrolled in the cohort, and 11,193 completed a home visit. Most were young (56.2% ≤ 45 years of age), male (80.8%), lived in a Gulf state (82.3%), and worked at least 1 day on the oil spill (76.5%). Workers were involved in response (18.0%), support operations (17.5%), clean-up on water (17.4%) or land (14.6%), decontamination (14.3%), and administrative support (18.3%). Using an ordinal job exposure matrix, 45% had maximum daily total hydrocarbon exposure levels ≥ 1.0 ppm. The GuLF STUDY provides a unique opportunity to study potential adverse health effects from the oil spill.

Limited prior data suggest an association between traffic-related air pollution and incident asthma in adults. No published studies assess the effect of long-term exposures to particulate matter less than 2.5 μm in diameter (PM2.5) on adult incident asthma. To estimate the association between ambient air pollution exposures (PM2.5 and nitrogen dioxide, NO2) and development of asthma and incident respiratory symptoms. The Sister Study is a U.S. cohort study of risk factors for breast cancer and other health outcomes (n = 50,884) in sisters of women with breast cancer (enrollment, 2003-2009). Annual average (2006) ambient PM2.5 and NO2 concentrations were estimated at participants' addresses, using a national land-use/kriging model incorporating roadway information. Outcomes at follow-up (2008-2012) included incident self-reported wheeze, chronic cough, and doctor-diagnosed asthma in women without baseline symptoms. Adjusted analyses included 254 incident cases of asthma, 1,023 of wheeze, and 1,559 of chronic cough. For an interquartile range (IQR) difference (3.6 μg/m(3)) in estimated PM2.5 exposure, the adjusted odds ratio (aOR) was 1.20 (95% confidence interval [CI] = 0.99-1.46, P = 0.063) for incident asthma and 1.14 (95% CI = 1.04-1.26, P = 0.008) for incident wheeze. For NO2, there was evidence for an association with incident wheeze (aOR = 1.08, 95% CI = 1.00-1.17, P = 0.048 per IQR of 5.8 ppb). Neither pollutant was significantly associated with incident cough (PM2.5: aOR = 0.95, 95% CI = 0.88-1.03, P = 0.194; NO2: aOR = 1.00, 95% CI = 0.93-1.07, P = 0.939). Results suggest that PM2.5 exposure increases the risk of developing asthma and that PM2.5 and NO2 increase the risk of developing wheeze, the cardinal symptom of asthma, in adult women.

Objectives Recent meta-analyses suggest a physical activity health paradox: high levels of occupational physical activity (OPA) increase cardiovascular disease (CVD) risk, while leisure-time physical activity (LTPA) decreases risk. However, studies of women and cerebrovascular disease are limited. This report examines physical activity effects on stroke and transient ischemic attack (TIA) among working women in the United States. Methods OPA history, health status, and lifestyle were assessed by baseline interviews of 31 270 employed Sister Study participants aged 35-74 years. OPA was assessed at six intensity levels (lowest: \"mostly sitting\"); the highest three were combined as \"high intensity work.\" Independent OPA and LTPA effects on 6-year cerebrovascular disease incidence were estimated in adjusted Cox proportional hazard models. Results Stroke (N=441) and TIA (N=274) risk increased with more standing and higher intensity work at current and longest held job. Compared with mostly sitting, high intensity work at the current job increased TIA risk by 57% [hazard ratio (HR) 1.57, 95% confidence interval (CI) 1.04-2.38]. High intensity OPA at the longest held job increased risk for stroke by 44% (HR 1.44; 95% CI 1.08-1.93). Among women with CVD, sitting and standing equally, especially at the current job, increased risks up to two-fold (TIA HR 1.98, 95% CI 1.10-3.55) compared with mostly sitting at work. LTPA showed inverse associations. Conclusions Higher intensity levels of OPA increased stroke and TIA risks, while LTPA decreased risks; results corroborate the physical activity health paradox for women and cerebrovascular disease. More standing at work increased cerebrovascular disease risks, especially for women with CVD.

Background Vitamin D has anticarcinogenic and immune-related properties and may protect against some diseases, including breast cancer. Vitamin D affects gene transcription and may influence DNA methylation. Methods We studied the relationships between serum vitamin D, DNA methylation, and breast cancer using a case-cohort sample (1070 cases, 1277 in subcohort) of non-Hispanic white women. For our primary analysis, we used robust linear regression to examine the association between serum 25-hydroxyvitamin D (25(OH)D) and methylation within a random sample of the cohort (“subcohort”). We focused on 198 CpGs in or near seven vitamin D-related genes. For these 198 candidate CpG loci, we also examined how multiplicative interactions between methylation and 25(OH)D were associated with breast cancer risk. This was done using Cox proportional hazards models and the full case-cohort sample. We additionally conducted an exploratory epigenome-wide association study (EWAS) of the association between 25(OH)D and DNA methylation in the subcohort. Results Of the CpGs in vitamin D-related genes, cg21201924 ( RXRA ) had the lowest p value for association with 25(OH)D ( p  = 0.0004). Twenty-two other candidate CpGs were associated with 25(OH)D ( p  < 0.05; RXRA , NADSYN1/DHCR7 , GC , or CYP27B1 ). We observed an interaction between 25(OH)D and methylation at cg21201924 in relation to breast cancer risk (ratio of hazard ratios = 1.22, 95% confidence interval 1.10–1.34; p  = 7 × 10 −5 ), indicating a larger methylation-breast cancer hazard ratio in those with high serum 25(OH)D concentrations. We also observed statistically significant ( p  < 0.05) interactions for six other RXRA CpGs and CpGs in CYP24A1 , CYP27B1 , NADSYN1/DHCR7 , and VDR . In the EWAS of the subcohort, 25(OH)D was associated ( q  < 0.05) with methylation at cg24350360 ( EPHX1 ; p  = 3.4 × 10 −8 ), cg06177555 ( SPN ; p  = 9.8 × 10 −8 ), and cg13243168 ( SMARCD2 ; p  = 2.9 × 10 −7 ). Conclusions 25(OH)D concentrations were associated with DNA methylation of CpGs in several vitamin D-related genes, with potential links to immune function-related genes. Methylation of CpGs in vitamin D-related genes may interact with 25(OH)D to affect the risk of breast cancer.

Farming and pesticide use have previously been linked to non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). We evaluated agricultural use of specific insecticides, fungicides, and fumigants and risk of NHL and NHL-subtypes (including CLL and MM) in a U.S.-based prospective cohort of farmers and commercial pesticide applicators. A total of 523 cases occurred among 54,306 pesticide applicators from enrollment (1993-97) through December 31, 2011 in Iowa, and December 31, 2010 in North Carolina. Information on pesticide use, other agricultural exposures and other factors was obtained from questionnaires at enrollment and at follow-up approximately five years later (1999-2005). Information from questionnaires, monitoring, and the literature were used to create lifetime-days and intensity-weighted lifetime days of pesticide use, taking into account exposure-modifying factors. Poisson and polytomous models were used to calculate relative risks (RR) and 95% confidence intervals (CI) to evaluate associations between 26 pesticides and NHL and five NHL-subtypes, while adjusting for potential confounding factors. For total NHL, statistically significant positive exposure-response trends were seen with lindane and DDT. Terbufos was associated with total NHL in ever/never comparisons only. In subtype analyses, terbufos and DDT were associated with small cell lymphoma/chronic lymphocytic leukemia/marginal cell lymphoma, lindane and diazinon with follicular lymphoma, and permethrin with MM. However, tests of homogeneity did not show significant differences in exposure-response among NHL-subtypes for any pesticide. Because 26 pesticides were evaluated for their association with NHL and its subtypes, some chance finding could have occurred. Our results showed pesticides from different chemical and functional classes were associated with an excess risk of NHL and NHL subtypes, but not all members of any single class of pesticides were associated with an elevated risk of NHL or NHL subtypes. These findings are among the first to suggest links between DDT, lindane, permethrin, diazinon and terbufos with NHL subtypes.