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Background Gynecologic surgery is hypothesized to reduce risk of breast cancer; however, associations may be modified by subsequent hormone use. Our objective was to examine the association between gynecologic surgery and breast cancer incidence considering the use of hormone therapy. Methods The Sister Study is a prospective cohort of initially breast cancer–free women aged 35-74 years with a sister who had breast cancer. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between gynecologic surgery (no surgery, hysterectomy only, bilateral oophorectomy with or without hysterectomy) and incident breast cancer among 50 701 women. Results History of gynecologic surgery was common, with 13.8% reporting hysterectomy only and 18.1% reporting bilateral oophorectomy with or without hysterectomy. During follow-up (median = 11.4 years), 3948 cases were diagnosed. Compared with no surgery, bilateral oophorectomy was inversely associated with breast cancer (HR = 0.91, 95% CI = 0.83 to 1.00), and hysterectomy alone was positively associated (HR = 1.12, 95% CI = 1.02 to 1.23). Compared with no surgery and no hormone therapy, bilateral oophorectomy combined with estrogen only therapy (HR = 0.83, 95% CI = 0.74 to 0.94) was inversely associated with breast cancer, while hysterectomy combined with estrogen plus progestin therapy was positively associated with breast cancer (HR = 1.25, 95% CI = 1.01 to 1.55). Conclusions We observed an inverse association between bilateral oophorectomy and breast cancer risk. The positive association between hysterectomy and breast cancer may be due to concomitant estrogen plus progestin therapy. [ABSTRACT FROM AUTHOR]

BACKGROUND: During the 2010 Deepwater Horizon (DWH) disaster, response and cleanup workers were potentially exposed to toxic volatile components of crude oil. However, to our knowledge, no study has examined exposure to individual oil spill–related chemicals in relation to cardiovascular outcomes among oil spill workers. OBJECTIVES: Our aim was to investigate the association of several spill-related chemicals [benzene, toluene, ethylbenzene, xylene, 푛-hexane (BTEX-H)] and total hydrocarbons (THC) with incident coronary heart disease (CHD) events among workers enrolled in a prospective cohort. METHODS: Cumulative exposures to THC and BTEX-H across the cleanup period were estimated via a job-exposure matrix that linked air measurement data with self-reported DWH spill work histories. We ascertained CHD events following each worker’s last day of cleanup work as the first self-reported physician-diagnosed myocardial infarction (MI) or a fatal CHD event. We estimated hazard ratios (HR) and 95% confidence intervals for the associations of exposure quintiles (Q) with risk of CHD. We applied inverse probability weights to account for bias due to confounding and loss to follow-up. We used quantile g-computation to assess the joint effect of the BTEX-H mixture. RESULTS: Among 22,655 workers with no previous MI diagnoses, 509 experienced an incident CHD event through December 2019. Workers in higher quintiles of each exposure agent had increased CHD risks in comparison with the referent group (Q1) of that agent, with the strongest associations observed in Q5 (range of HR = 1.14–1:44). However, most associations were nonsignificant, and there was no evidence of exposure–response trends. We observed stronger associations among ever smokers, workers with =high school education, and workers with body mass index <30 kg/m². No apparent positive association was observed for the BTEX-H mixture. CONCLUSIONS: Higher exposures to volatile components of crude oil were associated with modest increases in risk of CHD among oil spill workers, although we did not observe exposure–response trends. [ABSTRACT FROM AUTHOR]

• Vitamin D status has been inconsistently associated with age of menopause. • We used data from the Sister Study cohort (N=13, 102). • We examined vitamin D or calcium supplement use and 25-hydroxyvitamin D (25OHD) level with the timing of natural menopause. • Concomitant multivitamin and vitamin D use was associated with slightly earlier menopause (HR(CI): 1.10 (0.98, 1.24). • None of the remaining vitamin D or calcium supplement variables meaningfully associated with timing of natural menopause. • Future studies of menopause timing should focus on a life course approach and include 25OHD measures from early mid-life. Vitamin D status has been inconsistently associated with ovarian reserve and menopause. We used data from the Sister Study cohort to examine the associations of vitamin D supplement use, total 25-hydroxyvitamin D (25OHD) level, and calcium supplement use with the timing of natural menopause. Vitamin D and calcium supplement use were assessed on a questionnaire at baseline (mean age: 46) and two follow-up time points, and characterized in multiple ways based on type, dose, and duration of use. Serum samples from a random subset of participants were analyzed for total 25OHD (25OHD 3 + 25OHD 2 + epi-25OHD 3) using liquid chromatography-mass spectrometry. Menopause was assessed at each yearly follow-up with the question "Have you had a menstrual period in the past 12 months?"; if the response was "no", age at last menstrual period was recorded. We censored women at time of hysterectomy or medically induced menopause, death, loss to follow-up or October 2020. We used multivariable Cox proportional hazard models with age as the time scale to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs), adjusting for race/ethnicity, education, body mass index, alcohol use, smoking status, and physical activity. Among the 13,102 eligible premenopausal participants, 8897 experienced natural menopause during follow-up. Concomitant use of a multivitamin and a vitamin D supplement was associated with slightly earlier menopause (HR(CI): 1.10 (0.98, 1.24)). None of the remaining vitamin D or calcium supplement variables (alone or in combination) were meaningfully associated with timing of natural menopause. In a subsample with 25OHD measurements (n = 906), neither total 25OHD nor 25OHD 3 was associated with timing of menopause. Our study includes, on average, 6 years of follow-up from an average age of 46 years and did not find associations between vitamin D or calcium supplement use and timing of menopause. Future studies should focus on a life course approach to this question and include 25OHD measures from early mid-life when examining menopause timing. [ABSTRACT FROM AUTHOR]

We evaluated whether hair products, which may contain carcinogens and endocrine disruptors that can be absorbed into the bloodstream, are related to ovarian cancer incidence in a prospective cohort. After excluding women with a history of ovarian cancer or bilateral oophorectomy, 40 559 Sister Study participants ages 35–74 at enrollment (2003–2009) were included. Participants completed questionnaires on hair product use, including hair dyes, straighteners/relaxers and permanents/body waves, in the past 12 months. Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between hair products and incident ovarian cancer. We assessed associations stratified by tumor type (serous, non-serous). Over a mean follow-up of 10 years, 241 women were diagnosed with ovarian cancer. Ever use of any of the examined hair products during the past year was not associated with ovarian cancer risk. However, frequent use (>4 times/year) of straighteners/relaxers or pressing products in the past year was associated with an increased risk of ovarian cancer (HR = 2.19, 95% CI: 1.12–4.27). Ever use of permanent hair dye was positively associated with non-serous (HR = 1.94, 95% CI 1.12–3.37), but inversely associated with serous (HR = 0.65, 95% CI: 0.43–0.99) tumors (p -for-heterogeneity = 0.002). Our novel findings suggest that frequent use of hair straighteners/relaxers or pressing products, which are primarily used by African American/Black women, and possibly permanent hair dye, may be associated with the occurrence of ovarian cancers. [ABSTRACT FROM AUTHOR]

Background: Peripheral blood DNA methylation may be associated with breast cancer, but studies of candidate genes and global and genome-wide DNA methylation have been inconsistent.Methods: We performed an epigenome-wide study using Infinium HumanMethylation450 BeadChips with prospectively collected blood DNA samples from the Sister Study (1552 cases, 1224 subcohort). Differentially methylated cytosine-phosphate-guanine sites (dmCpGs) were identified using case-cohort proportional hazard models and replicated using deposited data from European Prospective Investigation into Cancer and Nutrition in Italy (EPIC-Italy) (n = 329). The correlation between methylation and time to diagnosis was examined using robust linear regression. Causal or consequential relationships of methylation to breast cancer were examined by Mendelian randomization using OncoArray 500 K single-nucleotide polymorphism data. All statistical tests were two-sided.Results: We identified 9601 CpG markers associated with invasive breast cancer (false discovery rate = q < 0.01), with 510 meeting a strict Bonferroni correction threshold (10-7). A total of 2095 of these CpGs replicated in the independent EPIC-Italy dataset, including 144 meeting the Bonferroni threshold. Sister Study women who developed ductal carcinoma in situ had methylation similar to noncases. Most (1501, 71.6%) dmCpGs showed lower methylation in invasive cases. In case-only analysis, methylation was statistically significantly associated (false discovery rate = q < 0.05) with time to diagnosis for 892 (42.6%) of the dmCpGs. Analyses based on genetic association suggest that methylation differences are likely a consequence rather than a cause of breast cancer. Pathway analysis shows enrichment of breast cancer-related gene pathways, and dmCpGs are overrepresented in known breast cancer susceptibility genes.Conclusions: Our findings suggest that the DNA methylation profile of blood starts to change in response to invasive breast cancer years before the tumor is clinically detected. [ABSTRACT FROM AUTHOR]

Purpose: We assessed the cross-sectional association between healthy dietary patterns [alternate Mediterranean diet (aMED), Dietary Approaches to Stop Hypertension (DASH), alternative Healthy Eating Index (aHEI), and Healthy Eating Index 2015 (HEI-2015)] and urinary biomarkers of oxidative stress. Methods: Between 2003 and 2009, the Sister Study enrolled 50,884 breast cancer-free US women aged 35 to 74 (non-Hispanic White, 83.7%). Data were analyzed for 844 premenopausal and 454 postmenopausal women who had urine samples analyzed for F2-isoprostanes and non-missing covariate data. Food frequency questionnaire responses were used to calculate dietary pattern scores. Concentrations of 8-iso-prostaglandin F2α (8-iso-PGF2α) and its metabolite (8-iso-PGF2α-M) were measured in urine samples by GC/MS for premenopausal women and LC/MS for postmenopausal women. Multivariable linear regression models were used to estimate associations between aMED, DASH, aHEI, and HEI-2015 and urinary F2-isoprostanes by menopausal status. Effect modification by sociodemographic, lifestyle, and clinical characteristics was also evaluated. Results: Among premenopausal women, the four dietary indices were inversely associated with 8-iso-PGF2α (aMED βQ4vsQ1: − 0.17, 95% CI − 0.27, − 0.08; DASH βQ4vsQ1: − 0.18, 95% CI − 0.28, − 0.08; aHEI βQ4vsQ1: − 0.20, 95% CI − 0.30, − 0.10; HEI-2015 βQ4vsQ1: − 0.19, 95% CI − 0.29, − 0.10). In contrast, inverse associations with 8-iso-PGF2α-M were found for the continuous aMED, aHEI, and HEI-2015. Associations between dietary indices and 8-iso-PGF2α were generally stronger among younger women, women with lower income, and women with higher BMI. Similar results were observed among postmenopausal women, though only the continuous DASH and aHEI models were statistically significant. Conclusion: Healthy dietary patterns were associated with lower levels of oxidative stress. [ABSTRACT FROM AUTHOR]

BACKGROUND: Atrazine is a common agricultural herbicide in the United States. Few epidemiologic studies have evaluated cancer risks. Previous analyses within the Agricultural Health Study (AHS) have found some evidence of associations with cancer at some sites. OBJECTIVE: We updated exposure information, incident cases, and follow-up time to assess the associations between atrazine use and cancer at specific sites in the AHS. METHODS: Information about lifetime pesticide use was reported at enrollment (1993–1997) and follow-up (1999–2005). Among 53,562 pesticide applicators in North Carolina and Iowa, we identified 8,915 incident cases through cancer registry linkages through 2014 (North Carolina)/2017 (Iowa). We used Poisson regression to evaluate the association between ever/never and intensity-weighted lifetime days of atrazine use and incident cancer risk controlling for several confounders. We also evaluated lagged exposures and age-stratified risk. RESULTS: Approximately 71.2% of applicators reported ever using atrazine, which was associated with lung cancer [rate ratios(RR)= 1.24; 95% confidence interval (CI): 1.04, 1.46]. Aggressive prostate cancer risk was increased in the highest quartile (RRQ4 = 1.20; 95% CI: 0.95, 1.52; 푝-trend = 0.19), particularly among those <60 years old (RRQ4 = 3.04; 95% CI: 1.61, 5.75; 푝-trend <0.001; 푝-interaction = 0.04). Among applicators <50 years of age, ever-atrazine use was associated with non-Hodgkin lymphoma (NHL) (RR = 2.43; 95% CI: 1.10, 5.38; 푝-interaction = 0.60). For soft tissue sarcoma, there was an elevated risk in the highest tertile of exposure (RRT3: 2.54; 95% CI: 0.97, 6.62; 푝-trend = 0.31). In analyses with exposure lagged by 25 years, there was an elevated risk of pharyngeal (RRT3 = 3:04; 95% CI: 1.45, 6.36; 푝-trend = 0.07) and kidney (RRQ4 = 1.62; 95% CI: 1.15, 2.29; 푝-trend <0:005) cancers. DISCUSSION: We observed suggestive associations with some malignancies in overall, age-specific, and lagged analyses. Associations with aggressive prostate cancer and NHL were apparent among those diagnosed at younger ages and with cancers of the pharynx and kidney, and soft tissue sarcomas were observed in lagged analyses. Further work is needed to confirm these observed associations and elucidate potential underlying mechanisms [ABSTRACT FROM AUTHOR]

With the threat of climate change looming, the public health community has an interest in identifying communities at the highest risk of devastation based not only on geographic features but also on social characteristics. Indices of community social vulnerability can be created by applying a spatial factor analysis to a set of relevant social variables measured for each community; however, current spatial factor analysis methodology is ill-equipped to handle spatially misaligned data. We introduce a joint spatial factor analysis model that can accommodate spatial data from two distinct partitions of a geographic space and identify a common set of latent factors underlying them. By defining the latent factors over the intersection of the two partitions, the model minimizes loss of information. Using simulated data constructed to mimic the spatial structure of our real data, we confirm the reliability of the model and demonstrate its superiority over competing ad hoc methods for dealing with misaligned data in spatial factor analysis. Finally, we construct an index of community social vulnerability for each census tract in Louisiana, a state prone to environmental disasters, which could be exacerbated by climate change, by applying the joint spatial factor analysis model to a set of misaligned social indicator data from the state. To demonstrate the utility of this index, we integrate it with Louisiana flood insurance claims data to identify communities that may be at particularly high risk during natural disasters, based on both social and geographic features. [ABSTRACT FROM AUTHOR]

Exposure to total hydrocarbons (THC) and volatile organic compounds from air pollution is associated with risk of coronary heart disease. THC exposure from oil spills might be similarly associated, but no research has examined this. We assessed the relationship between THC exposure during the response and cleanup of the Deepwater Horizon oil spill (Gulf of Mexico) and heart attack risk among 24,375 oil spill workers enrolled in the Gulf Long-Term Follow-up Study. There were 312 first heart attacks (self-reported physician-diagnosed myocardial infarction, or fatal coronary heart disease) ascertained during the study period (2010–2016). THC exposures were estimated using a job-exposure matrix incorporating self-reported activities and personal air measurements. We used Cox proportional hazards regression to estimate hazard ratios, with inverse-probability weights to account for confounding and censoring. Maximum THC levels of ≥0.30 parts per million (ppm) were associated with heart attack risk, with a 1.8-fold risk for exposure of ≥3.00 ppm versus <0.30 ppm (hazard ratio = 1.81, 95% confidence interval: 1.11, 2.95). The risk difference for highest versus lowest THC level was 10 excess cases per 1,000 workers. This is the first study of the persistent health impacts of THC exposure during oil spill work, and results support increased protection against oil exposure during cleanup of future spills. [ABSTRACT FROM AUTHOR]

Prospective and retrospective studies of vitamin D levels and breast cancer have produced discrepant results. This may be due to variations in serum 25-hydroxyvitamin D (25(OH)D) concentrations over time, including systematic changes after breast cancer diagnosis. We measured total serum 25(OH)D levels in participants from the Sister Study, a US cohort study of sisters of breast cancer patients, who provided samples at baseline (2003–2009) and 4–10 years later (2013–2015). This included 827 women with an intervening breast cancer and 771 women without one. Although 25(OH)D levels were modestly correlated over time (R = 0.42), 25(OH)D concentrations increased in both groups, with larger increases among cases (averaging 31.6 ng/mL at baseline and 43.5 ng/mL at follow-up) than among controls (32.3 ng/mL at baseline, 40.4 ng/mL at follow-up). Consequently, the estimated association between 25(OH)D and breast cancer depended on whether baseline measurements (per 10-ng/mL increase, odds ratio = 0.87, 95% confidence interval: 0.78, 0.98) or measurements from the second blood draw (per 10-ng/mL increase, odds ratio = 1.17, 95% confidence interval: 1.08, 1.26) were used. Concentrations were related to regular use (≥4 times/week) of vitamin D supplements, which became more common over time; increases in regular use were greater in cases (from 56% to 84%) than in controls (from 56% to 77%). Our results do not explain previously observed differences between retrospective and prospective studies, but they do demonstrate how reverse causation and temporal trends in exposure can distort inference. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although styrene is an established neurotoxicant at occupational exposure levels, its neurotoxicity has not been characterized in relation to general population exposures. Further, occupational research to date has focused on central nervous system impairment. OBJECTIVE: We assessed styrene-associated differences in sensory and motor function among Gulf coast residents. METHODS: We used 2011 National Air Toxics Assessment estimates of ambient styrene to determine exposure levels for 2,956 nondiabetic Gulf state residents enrolled in the Gulf Long-term Follow-up Study, and additionally measured blood styrene concentration in a subset of participants 1 to 2 y after enrollment (n=310). Participants completed an enrollment telephone interview and a comprehensive test battery to assess sensory and motor function during a clinical follow-up exam 2 to 4 y later. Detailed covariate information was ascertained at enrollment via telephone interview. We used multivariate linear regression to estimate continuous differences in sensory and motor function, and log-binomial regression to estimate prevalence ratios for dichotomous outcomes. We estimated associations of both ambient and blood styrene exposures with sensory and motor function, independently for five unique tests. RESULTS: Those participants in the highest 25% vs. lowest 75% of ambient exposure and those in the highest 10% vs. lowest 90% of blood styrene had slightly diminished visual contrast sensitivity. Mean vibrotactile thresholds were lower among those in the highest vs. lowest quartile of ambient styrene and the highest 10% vs. lowest 90% of blood styrene (-0:13 log microns; 95% CI: -0:23, -0:03 and -0:39 log microns; 95% CI: -0:72, -0:05, respectively). The highest vs. lowest quartile of ambient styrene was associated with significantly poorer postural stability, and (unexpectedly) with significantly greater grip strength. DISCUSSION: We observed associations between higher styrene exposure and poorer visual, sensory, and vestibular function, though we did not detect associations with reduced voluntary motor system performance. Associations were more consistent for ambient exposures, but we also found notable associations with measured blood styrene. [ABSTRACT FROM AUTHOR]

The randomized Vitamin D and Omega-3 Trial (VITAL) was underpowered to study breast cancer incidence, with only 246 breast cancer cases diagnosed at the time of analysis.12 Furthermore, the VITAL trial allowed personal supplement use, which would bias the effect toward the null. Women who identify as members of these racial/ethnic groups have lower blood vitamin D concentrations on average than non-Hispanic White women, and the potential health-related consequences of racial/ethnic differences in vitamin D are not understood. [Extracted from the article]

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: The Sister Study enrolled 50,884 U.S. and Puerto Rican women 35-74 y 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 <30 y of age (79%), never-smokers (56%) with body mass indexes (BMIs) of <29:9 kg=m² (70%). Few (5%) reported any cancer prior to enrollment. CONCLUSIONS: 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. [ABSTRACT FROM AUTHOR]

BACKGROUND: Indoor burning of fuel for heating or cooking releases carcinogens. Little is known about the impact of indoor air pollution from wood-burning stoves or fireplaces on breast cancer risk. OBJECTIVES: In a large prospective cohort study, we evaluated the risk of breast cancer in relation to indoor heating and cooking practices. METHODS: Sister Study participants (n=50,884) were recruited from 2003-2009. Breast cancer-free women in the United States or Puerto Rico, 35-74 y old, with a sister with breast cancer were eligible. Participants completed questionnaires on indoor heating and cooking practices for both their enrollment and their longest adult residence. Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association between indoor heating/cooking and breast cancer. RESULTS: A total of 2,416 breast cancer cases were diagnosed during follow-up (mean=6:4 y). Having an indoor wood-burning stove/fireplace in the longest adult residence was associated with a higher breast cancer risk [HR=1:11 (95% CI: 1.01, 1.22)]; the risk increased with average frequency of use [=once=week, HR=1:17 (95% CI: 1.02, 1.34)] (p for trend=0:01). An elevated HR was seen for women burning wood [HR=1:09 (95% CI: 0.98, 1.21)] or natural gas/propane [HR=1:15 (95% CI: 1.00, 1.32)]. No association was observed for burning artificial fire-logs [HR=0:98 (95% CI: 0.85, 1.12)] except among women from western states [HR=1:36 (95% CI: 1.02, 1.81)]. CONCLUSIONS: In this prospective study, using an indoor wood-burning stove/fireplace in the longest adult residence at least once a week and burning either wood or natural gas/propane was associated with a modestly higher risk of breast cancer. [ABSTRACT FROM AUTHOR]

BACKGROUND: Vitamin D is an environmental and dietary agent with known anticarcinogenic effects, but protection against breast cancer has not been established. OBJECTIVE: We evaluated the association between baseline serum 25-hydroxyvitamin D [25(OH)D] levels, supplemental vitamin D use, and breast cancer incidence over the subsequent 5 y of follow-up. METHODS: From 2003-2009, the Sister Study enrolled 50,884 U.S. women 35-74 y old who had a sister with breast cancer but had never had breast cancer themselves. Using liquid chromatography-mass spectrometry, we measured 25(OH)D in serum samples from 1,611 women who later developed breast cancer and from 1,843 randomly selected cohort participants. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of developing breast cancer using Cox proportional hazards models. RESULTS: We found that 25(OH)D levels >38:0 ng=mL were associated with a 21% lower breast cancer hazard (highest versus lowest quartile: adjusted HR=0:79; CI: 0.63, 0.98). Analysis of the first 5 y of follow-up for all 50,884 Sister Study participants showed that self-reported vitamin D supplementation =4 times=wk was associated with an 11% lower hazard [HR=0:89 (CI: 0.81, 0.99)]. These associations were particularly strong among postmenopausal women [HR=0:72 (CI: 0.57, 0.93) and HR=0:83 (CI: 0.74, 0.93), respectively]. CONCLUSIONS: In this cohort of women with elevated risk, high serum 25(OH)D levels and regular vitamin D supplement use were associated with lower rates of incident, postmenopausal breast cancer over 5 y of follow-up. These results may help to establish clinical benchmarks for 25(OH)D levels; in addition, they support the hypothesis that vitamin D supplementation is useful in breast cancer prevention. [ABSTRACT FROM AUTHOR]

BACKGROUND: The occupation of farming has been associated with rheumatoid arthritis (RA); pesticides may account for this association, but there are few studies. OBJECTIVES: We investigated associations between RA and use of pesticides in the Agricultural Health Study. METHODS: The study sample was drawn from male pesticide applicators enrolled in 1993-1997 who provided questionnaire data at baseline and at least once during follow-up (over a median 18 y; interquartile range 16-19). Incident RA cases (n=220), confirmed by physicians or by self-reported use of disease-modifying antirheumatic drugs, were compared with noncases (n=26,134) who did not report RA. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression, adjusting for enrollment age, state, smoking pack-years, and education. We evaluated the association of RA with the use of 46 pesticides and across 4 levels (never use and tertiles) of lifetime days of use for 16 pesticides with OR≥1:2 for ever use. RESULTS: Incident RA was associated with ever use of fonofos (OR = 1.70; 95% CI: 1.22, 2.37), carbaryl (OR = 1.51; 95% CI: 1.03, 2.23), and chlorimuron ethyl (OR = 1.45; 95% CI: 1.01, 2.07) compared with never use. Statistically significant exposure--response trends in association with RA were observed for lifetime days of use of atrazine [ORtertile3 = 1.62 (95% CI: 1.09, 2.40); ptrend =0:01] and toxaphene [ORtertile3 = 2.42 (95% CI: 1.03, 5.68); ptrend =0:02]. Exposure--response was nonlinear for fonofos [ORtertil13 = 2.27 (95% CI: 1.44, 3.57); ORtertile2 = 0.98 (95% CI: 0.54, 1.80); ORtertile3 = 2.10 (95% CI: 1.32, 3.36); ptrend =0:005] and suggestive for carbaryl (ptrend =0:053). CONCLUSIONS: Our results provide novel evidence of associations between exposure to some pesticides and RA in male farmers. [ABSTRACT FROM AUTHOR]

During the 2010 Deepwater Horizon (DWH) disaster, in-situ burning and flaring were conducted to remove oil from the water. Workers near combustion sites were potentially exposed to burning-related fine particulate matter (PM 2.5). Exposure to PM 2.5 has been linked to increased risk of coronary heart disease (CHD), but no study has examined the relationship among oil spill workers. To investigate the association between estimated PM 2.5 from burning/flaring of oil/gas and CHD risk among the DWH oil spill workers. We included workers who participated in response and cleanup activities on the water during the DWH disaster (N = 9091). PM 2.5 exposures were estimated using a job-exposure matrix that linked modelled PM 2.5 concentrations to detailed DWH spill work histories provided by participants. We ascertained CHD events as the first self-reported physician-diagnosed CHD or a fatal CHD event that occurred after each worker's last day of burning exposure. We estimated hazard ratios (HR) and 95% confidence intervals (95%CI) for the associations between categories of average or cumulative daily maximum PM 2.5 exposure (versus a referent category of water workers not near controlled burning) and subsequent CHD. We assessed exposure-response trends by examining continuous exposure parameters in models. We observed increased CHD hazard among workers with higher levels of average daily maximum exposure (low vs. referent: HR = 1.26, 95% CI: 0.93, 1.70; high vs. referent: HR = 2.11, 95% CI: 1.08, 4.12; per 10 μg/m3 increase: HR = 1.10, 95% CI: 1.02, 1.19). We also observed suggestively elevated HRs among workers with higher cumulative daily maximum exposure (low vs. referent: HR = 1.19, 95% CI: 0.68, 2.08; medium vs. referent: HR = 1.38, 95% CI: 0.88, 2.16; high vs. referent: HR = 1.44, 95% CI: 0.96, 2.14; per 100 μg/m3-d increase: HR = 1.03, 95% CI: 1.00, 1.05). Among oil spill workers, exposure to PM 2.5 from flaring/burning of oil/gas was associated with increased risk of CHD. • In the Deepwater Horizon disaster, controlled burning of oil/gas produced PM 2.5. • Many oil spill workers were exposed to PM 2.5 levels above the EPA's daily standard. • PM 2.5 exposure was linked to higher risk of coronary heart disease among workers. • Increase in heart disease risk persisted up to 10 years after the burning exposure. [ABSTRACT FROM AUTHOR]

Objective: To evaluate exposure to tobacco, marijuana, and indoor heating/cooking sources in relation to antimüllerian hormone (AMH) levels.Design: Cross-sectional analysis in a sample of premenopausal women (n = 913) enrolled in the Sister Study cohort (n = 50,884).Setting: Not applicable.Patient(s): Women, ages 35-54 years at time of enrollment, with an archived serum sample and at least one intact ovary and classified as premenopausal.Intervention(s): Not applicable.Main Outcome Measure(s): Serum AMH (ng/mL) levels ascertained by ultrasensitive ELISA assay.Result(s): Lower AMH levels were associated with sources of indoor heating, including burning wood (-36.0%; 95% confidence interval [CI], -55.7%, -7.8%) or artificial fire logs (-45.8%; 95% CI, -67.2%, -10.4%) at least 10 times/year in a residential indoor stove/fireplace. Lower AMH levels were also observed in women who were current smokers of ≥20 cigarettes/day relative to nonsmokers (-56.2%; 95% CI, -80.3%, -2.8%) and in women with 10+ years of adult environmental tobacco smoke (ETS) exposure (-31.3%; 95% CI, -51.3%, -3.1%), but no associations were observed for marijuana use.Conclusion(s): We confirmed previously reported findings of lower AMH levels in current heavy smokers and also found associations for long-term ETS exposure and indoor burning of wood or artificial fire logs. These findings suggest that combustion by-products from common exposures can have toxic effects on the human ovary. [ABSTRACT FROM AUTHOR]

The relationship between type 2 diabetes (T2D), metformin, and breast cancer is complex. T2D may increase risk, but metformin used as first-line treatment of T2D may decrease breast cancer risk. This comment explores efforts to disentangle effects of T2D and metformin use on breast cancer risk in a prospective study. [ABSTRACT FROM AUTHOR]

The relationship between type 2 diabetes (T2D), metformin, and breast cancer is complex. T2D may increase risk, but metformin used as first-line treatment of T2D may decrease breast cancer risk. This comment explores efforts to disentangle effects of T2D and metformin use on breast cancer risk in a prospective study. [ABSTRACT FROM AUTHOR]

Objective: Evaluate the association between thyroid disease and use of insecticides, herbicides, and fumigants/fungicides in male applicators in the Agricultural Health Study. Methods: We examined the association between use of 50 specific pesticides and self-reported hypothyroidism, hy- perthyroidism, and "other" thyroid disease among 22,246 male pesticide applicators. Results: There was increased odds of hypothyroidism with ever use of the herbicides 2,4-D (2,4-dichlorophenoxyacetic acid), 2,4,5-T (2,4,5-trichlorophenoxyacetic acid), 2,4,5-TP (2,4,5-trichlorophenoxy- propionic acid), alachlor, dicamba, and petroleum oil. Hypothyroidism was also associated with ever use of eight insecticides: organochlorines chlordane, dichlorodiphenyltrichloroethane (DDT), heptachlor, lindane, and toxaphene; organophosphates diazinon and malathion; and the carbamate carbofuran. Exposure-response analysis showed increasing odds with increasing level of exposure for the herbicides alachlor and 2,4-D and the insecticides aldrin, chlordane, DDT, lindane, and parathion. Conclusion: There is an association between hypothyroidism and specific herbicides and insecticides in male applicators, similar to previous results for spouses. [ABSTRACT FROM AUTHOR]

Abstract: Background: DNA methylation patterns are heritable but can change over time and in response to exposures. Lower global DNA methylation, which may result in increased genomic and chromosomal instability, has been associated with increased cancer risk. Physical activity is a modifiable factor that has been inversely related to the risk of cancer. Changes in DNA methylation may be a mechanism by which lifestyle and environment factors influence disease. We investigated the relationship between DNA methylation and physical activity in a sample of women enroled in The Sister Study, a large United States (U.S.) cohort study of women aged 35–74years with a family history of breast cancer. Methods: Global DNA methylation was measured using bisulphite-converted DNA and pyrosequencing of a LINE-1 repetitive sequence in the peripheral blood of 647 non-Hispanic white women. Physical activity (average hours per week) was retrospectively assessed for three time periods: childhood (ages 5–12), teenage years (ages 13–19) and the previous 12months. Findings: Compared with women with physical activity levels below the median for all three time periods, those at or above the median physical activity for one (β =0.20, 95% confidence interval (CI): −0.10, 0.49), two (β =0.22, 95% CI: −0.08, 0.52) or all three (β =0.33, 95% CI: 0.01, 0.66) time periods had increased global methylation. Interpretation: Maintaining higher levels of physical activity over these three time periods was associated with increased global DNA methylation, consistent with reported associations between exercise and decreased cancer risk. [Copyright &y& Elsevier]

Background: Studies examining the association between telomere length and cancer risk have often relied on measurement of telomere length from a single blood draw using a real-time PCR technique. We examined the reliability of telomere length measurement using sequential samples collected over a 9-month period. Methods and Findings: Relative telomere length in peripheral blood was estimated using a single tube monochrome multiplex quantitative PCR assay in blood DNA samples from 27 non-pregnant adult women (aged 35 to 74 years) collected in 7 visits over a 9-month period. A linear mixed model was used to estimate the components of variance for telomere length measurements attributed to variation among women and variation between time points within women. Mean telomere length measurement at any single visit was not significantly different from the average of 7 visits. Plates had a significant systematic influence on telomere length measurements, although measurements between different plates were highly correlated. After controlling for plate effects, 64% of the remaining variance was estimated to be accounted for by variance due to subject. Variance explained by time of visit within a subject was minor, contributing 5% of the remaining variance. Conclusion: Our data demonstrate good short-term reliability of telomere length measurement using blood from a single draw. However, the existence of technical variability, particularly plate effects, reinforces the need for technical replicates and balancing of case and control samples across plates. [ABSTRACT FROM AUTHOR]

The article presents the relationship of myocardial infarction (MI) incidence and pesticide use among farm women in the Agricultural Health Study. It states that logistic regression analysis was utilized to assess pesticide use and the occurrence of nonfatal MI among these women while 6 out of 27 pesticides were assessed which showed a significant relationship with nonfatal MI including chlorpyrifos, coumaphos and carbofuran. It was found out that pesticides play a role in MI risk among women.

Long-chain ω-3 polyunsaturated fatty acids (PUFAs) may have antineoplastic properties in the colon. The authors examined the association between intakes of different PUFAs and distal large bowel cancer in a population-based case-control study of 1,503 whites (716 cases; 787 controls) and 369 African Americans (213 cases; 156 controls) in North Carolina (2001-2006). Unconditional logistic regression was used to estimate odds ratios and 95% confidence intervals for distal large bowel cancer risk in relation to quartiles of PUFA intake. Increased consumption of long-chain ω-3 PUFAs was associated with reduced risk of distal large bowel cancer in whites (multivariable odds ratios = 0.88 (95% confidence interval (CI): 0.63, 1.22), 0.69 (95% CI: 0.49, 0.98), and 0.49 (95% CI: 0.34, 0.71) for second, third, and highest vs. lowest quartile) (Ptrend < 0.01). Intake of individual eicosapentaenoic acids and docosahexaenoic acids was inversely related to distal large bowel cancer risk, whereas the ratio of ω-6 to long-chain ω-3 PUFAs was associated with increased risk of distal large bowel cancer in whites, but not among African Americans (Pinteraction < 0.05). Study results support the hypothesis that long-chain ω-3 PUFAs have beneficial effects in colorectal carcinogenesis. Whether or not the possible benefit of long-chain ω-3 PUFAs varies by race warrants further evaluation. [ABSTRACT FROM AUTHOR]

Thyroid disease is common, and evidence of an association between organochlorine exposure and thyroid disease is increasing. The authors examined the cross-sectional association between ever use of organochlorines and risk of hypothyroidism and hyperthyroidism among female spouses (n = 16,529) in Iowa and North Carolina enrolled in the Agricultural Health Study in 1993–1997. They also assessed risk of thyroid disease in relation to ever use of herbicides, insecticides, fungicides, and fumigants. Prevalence of self-reported clinically diagnosed thyroid disease was 12.5%, and prevalence of hypothyroidism and hyperthyroidism was 6.9% and 2.1%, respectively. There was an increased odds of hypothyroidism with ever use of organochlorine insecticides (adjusted odds ratio (ORadj) = 1.2 (95% confidence interval (CI): 1.0, 1.6) and fungicides (ORadj = 1.4 (95% CI: 1.1, 1.8) but no association with ever use of herbicides, fumigants, organophosphates, pyrethroids, or carbamates. Specifically, ever use of the organochlorine chlordane (ORadj = 1.3 (95% CI: 0.99, 1.7), the fungicides benomyl (ORadj = 3.1 (95% CI: 1.9, 5.1) and maneb/mancozeb (ORadj = 2.2 (95% CI: 1.5, 3.3), and the herbicide paraquat (ORadj = 1.8 (95% CI: 1.1, 2.8) was significantly associated with hypothyroidism. Maneb/mancozeb was the only pesticide associated with both hyperthyroidism (ORadj = 2.3 (95% CI: 1.2, 4.4) and hypothyroidism. These data support a role of organochlorines, in addition to fungicides, in the etiology of thyroid disease among female spouses enrolled in the Agricultural Health Study. [ABSTRACT FROM PUBLISHER]

Pesticides have been reported to be associated with malignant and non-malignant kidney disease. Few studies have examined the relationship between individual pesticides and kidney dysfunction. We evaluated the associations of pesticide use with measured kidney function among male pesticide applicators in the Biomarkers of Exposure and Effect in Agriculture (BEEA) study, a subcohort in the Agricultural Health Study. Serum creatinine was measured in 1545 BEEA participants and estimated glomerular filtration rate (eGFR) was calculated with the chronic kidney disease epidemiology collaboration (CKD-EPI) equation. Using reported information on lifetime use of 41 pesticides, multivariable linear and logistic regression was used to examine associations with eGFR modeled continuously and with CKD (eGFR <60 mL/min/1.73 m2), respectively. Models were adjusted for possible confounding factors related to kidney function and correlated pesticides. Lower eGFR was observed among pesticide applicators who ever used the herbicides pendimethalin (−3.7%, 95% confidence interval (CI): 5.8%, −1.5%), atrazine (−3.7%, 95% CI: 6.9%, −0.4%), and dicamba (−2.8%, 95% CI: 5.3%, −0.2%) compared with never users of each pesticide. Ever use of pendimethalin (odds ratio (OR)=1.6, 95% CI: 1.1, 2.2) and atrazine (OR=1.8, 95% CI: 1.0, 3.0) was also associated with elevated odds of CKD, with an exposure-response association between intensity-weighted lifetime days of pendimethalin use and CKD among active farmers (N=1302; p trend =0.04). Atrazine use within the last year was associated with lower eGFR and elevated odds of CKD when compared with never users, and we observed exposure-response associations with intensity-weighted lifetime days among recent users. Use of several other pesticides was associated with higher eGFR. These results suggest that two widely used herbicides, pendimethalin and atrazine, may be associated with altered kidney function among pesticide applicators. Our findings for these herbicides are consistent with observed associations with end-stage renal disease in the Agricultural Health Study. • Lifetime and recent atrazine use were associated with lower kidney function, with exposure-response trends among recent users. • Lifetime use of several other herbicides (pendimethalin, dicamba) was also associated with lower kidney function. • The observed associations with atrazine and pendimethalin are consistent with prior findings for advanced kidney disease. [ABSTRACT FROM AUTHOR]

Radon is a well-established cause of lung cancer in miners. Residents of homes with high levels of radon are potentially also at risk. Although most individual studies of indoor radon have failed to demonstrate significant risks, results have generally been consistent with estimates from studies of miners. We studied 1474 incident lung cancer cases aged 40–79 yr in Connecticut, Utah, and southern Idaho. Population controls (n = 1811) were identified by random telephone screening and from lists of Medicare recipients, and were selected to be similar to cases on age, gender, and smoking 10 yr before diagnosis/interview using randomized recruitment. Complete residential histories and information on known lung cancer risk factors were obtained by in-person and telephone interviews. Radon was measured on multiple levels of past and current homes using 12-mo alpha-track etch detectors. Missing data were imputed using mean radon concentrations for informative subgroups of controls. Average radon exposures were lower than anticipated, with median values of 23 Bq/m 3 in Connecticut and 45 Bq/m 3 in Utah/southern Idaho. Overall, there was little association between time-weighted average radon exposures 5 to 25 yr prior to diagnosis/interview and lung cancer risk. The excess relative risk (ERR) associated with a 100-Bq/m 3 increase in radon level was 0.002 (95% CI -0.21, 0.21) in the overall population, 0.134 (95% CI -0.23, 0.50) in Connecticut, and -0.112 (95% CI -0.34, 0.11) in Utah/Idaho. ERRs were higher for some subgroups less prone to misclassification, but there was no group with a statistically significant linear increase in risk. While results were consistent with the estimates from studies of miners, this study provides no evidence of an increased risk for lung cancer at the exposure levels observed. [ABSTRACT FROM AUTHOR]

Purpose: This analysis of the Agricultural Health Study cohort assesses the mortality experience of licensed pesticide applicators and their spouses. Methods: This report is based on 52,393 private applicators (who are mostly farmers) and 32,345 spouses of farmers in Iowa and North Carolina. At enrollment, each pesticide applicator completed a 21-page enrollment questionnaire. Mortality assessment from enrollment (1994–1997) through 2000 provided an average follow-up of about 5.3 years, 447,154 person-years, and 2055 deaths. Results: Compared with the general population in the two states, the cohort experienced a very low mortality rate. Standardized mortality ratios (SMRs) for total mortality, cardiovascular disease, diabetes, COPD, total cancer, and cancers of the esophagus, stomach, and lung were 0.6 or lower for both farmers and spouses. These deficits varied little by farm size, type of crops or livestock on the farm, years of handling pesticides, holding a non-farm job, or length of follow up. SMRs among ever smokers were not as low as among never smokers, but were still less than 1.0 for all smoking-related causes of death. No statistically significant excesses occurred, but slightly elevated SMRs, or those near 1.0, were noted for diseases that have been associated with farming in previous studies. Conclusions: Several factors may contribute to the low mortality observed in this population, including the healthy worker effect typically seen in cohorts of working populations (which may decline in future years), a short follow-up interval, and a healthier lifestyle manifested through lower cigarette use and an occupation that has traditionally required high levels of physical activity. [Copyright &y& Elsevier]

: PurposeTo examine the effects of lifestyle risk factors such as alcohol consumption, cigarette smoking and body mass index (BMI) on the development of chronic kidney disease.: MethodsWe used a case-control study of 554 hospital cases and 516 age, race, and gender-matched community controls. The main outcome measure was newly-diagnosed chronic kidney disease, assessed by chart review. Self-reported history of alcohol consumption, smoking, and BMI as well as other co-variables were obtained during telephone interviews. Logistic regression models assessed the association between lifestyle risk factors and chronic kidney disease and were adjusted for important co-variables.: ResultsWe found no significant associations between alcohol consumption and chronic kidney disease, with the exception of moonshine, which resulted in an increased risk of chronic kidney disease (including all subtypes). The effects of smoking on chronic kidney disease were inconsistent, but pointed to no appreciable excess risk among smokers. Increasing quartiles of BMI were positively and significantly associated with nephrosclerosis (ORs [95% CI]: 2.5 [1.0–6.0], 2.8 [1.2–6.8] and 4.6 [1.8–11.6], for the second, third, and fourth quartiles of BMI, respectively).: ConclusionsOur study revealed a significant positive association between BMI and nephrosclerosis. We did not find an increased risk of chronic kidney disease associated with alcohol or cigarette smoking. [Copyright &y& Elsevier]

Background Outdoor air pollution is a ubiquitous exposure that includes endocrine-disrupting and carcinogenic compounds that may contribute to the risk of hormone-sensitive outcomes such as uterine cancer. However, there is limited evidence about the relationship between outdoor air pollution and uterine cancer incidence. Methods We investigated the associations of residential exposure to particulate matter less than 2.5 µm in aerodynamic diameter (PM2.5) and nitrogen dioxide (NO2) with uterine cancer among 33 417 Sister Study participants with an intact uterus at baseline (2003-2009). Annual average air pollutant concentrations were estimated at participants' geocoded primary residential addresses using validated spatiotemporal models. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for the association between time-varying 12-month PM2.5 (µg/m3) and NO2 (parts per billion; ppb) averages and uterine cancer incidence. Results Over a median follow-up period of 9.8 years, 319 incident uterine cancer cases were identified. A 5-ppb increase in NO2 was associated with a 23% higher incidence of uterine cancer (hazard ratio = 1.23, 95% confidence interval = 1.04 to 1.46), especially among participants living in urban areas (hazard ratio = 1.53, 95% confidence interval = 1.13 to 2.07), but   PM2.5 was not associated with increased uterine cancer incidence. Conclusion In this large US cohort, NO2, a marker of vehicular traffic exposure, was associated with a higher incidence of uterine cancer. These findings expand the scope of health effects associated with air pollution, supporting the need for policy and other interventions designed to reduce air pollutant exposure. [ABSTRACT FROM AUTHOR]

We obtained data on smoking by parents from 438 cancer cases nd 470 controls to investigate whether cancer risk in adult life is related to transplacental or childhood exposure to cigarette smoke. Cancer cases were between ages 15 and 59 at time of diagnosis. All 'sites but basal cell cancer of the skin were included. Cancer risk was increased 50 per cent among offspring of men who smoked, increased risk associated with father's smoking was not explained by demographic factors social class, or individual smoking habits and was not limited to known smoking related sites. Relative risk (RR) estimates associated with father's smoking tended to be greatest for smokers, males, and non-Whites. There was only a slight increase in overall cancer risk associated with maternal smoking. Mother's and father's smoking were both associated with risk for hematopoietic cancers, and a dose-response relationship was seen. The RR for hematopoietic cancers increased flora 1.7 when one parent smoked to 4.6 when both parents smoked. Although they should be considered tentative study findings suggest a long-term hazard from transplacental or childhood passive exposure to cigarette smoke. (Am J Public Health 1985: 75:487-492.) [ABSTRACT FROM AUTHOR]

Objective: To evaluate the risk for chronic renal disease associated with regular use of nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs).Design: Multicenter case-control study.Patients: Patients were 554 North Carolina residents (age range, 30 to 79 years) hospitalized between 1980 and 1982 with a discharge diagnosis indicating newly diagnosed chronic renal dysfunction and a serum creatinine level consistently at or above 130 mumol/L (1.5 mg/dL). Controls were 516 persons chosen randomly by telephone screening (if younger than 65 years of age) and from listings of Medicare recipients (if 65 years of age or older), frequency-matched to patients by age, race, sex, and proximity to study hospitals.Measurements: Data on use of prescription NSAIDs and other analgesics before 1980, other risk factors, and potential confounders were obtained by telephone interviews. Patients were classified by frequency and duration of use; daily users were those who took an NSAID for at least 360 consecutive days.Main Results: A twofold risk for chronic renal disease was associated with previous daily use of NSAIDs (adjusted odds ratio, 2.1; 95% Cl, 1.1 to 4.1). Increased risk was predominantly limited to men older than 65 years, for whom the odds ratio for daily use was 10.0 (Cl, 1.2 to 82.7) after adjusting for use of other analgesics. In other age-sex groups, the risk associated with NSAID use tended to be increased among those with heart disease or other factors that might indicate compromised renal circulation. These findings did not result from confounding by known renal disease risk factors and were not readily explained by potential biases.Conclusions: Regular use of NSAIDs may increase the risk for chronic kidney disease in some high-risk groups. With the recent over-the-counter availability and increasing popularity of NSAIDs, the possibility of an increased risk for chronic renal disease associated with their use may warrant further scrutiny. [ABSTRACT FROM AUTHOR]

Mortality associated with passive smoking was evaluated in a 12-year study of 27,891 White adult smokers and 19,035 never smokers identified in 1963. Death rates were calculated using an estimate of the person-years at risk. Adjusted for age, marital status, education, and quality of housing, the estimated relative risks of death from all causes were 1.17 (approximate 95% confidence interval 1.01, 1.36) for men and 1.15 (1.06, 1.24) for women with passive exposure. These relative risks were similar to those for ex-smokers and for pipe or cigar smokers. Risks increased slightly with level of exposure. The relative risk from passive smoking was greatest for men under age 50 (RR = 2.09, 1.31-3.34). Risks from passive smoking were slightly elevated for several causes among men and women, and may be broader than those previously reported. On the other hand, these small nonspecific increases in death rates may reflect other characteristics of passive smokers that increase mortality. [ABSTRACT FROM AUTHOR]

Antinuclear antibodies (ANA), a marker of self-reactivity to DNA and other nuclear antigens, are present in several autoimmune diseases and have been observed in healthy persons in the absence of autoimmune disease. ANA prevalence is higher in women and older adults, but the health implications of ANA in middle- to older-aged adults are unknown. Immune system differences by sex may further result in sex-specific susceptibility to morbidity. In a cross-sectional analysis of data from the Baltimore Longitudinal Study of Aging, we examined the sex-specific relationship between age and ANA as well as the associations (odds ratios and 95% confidence intervals) between ANA and type-2 diabetes and multimorbidity (2 or more chronic diseases), stratified by sex and controlling for age and race. ANA was measured in a 1:160 dilution of sera by immunofluorescence using HEp-2 cells (seropositive = 3 or 4). Overall ANA seroprevalence was 12% (15.1% in women, 8.8% in men). We observed a non-linear relationship between age and ANA that varied by sex (interaction p -value < 0.05), with a clear sex differences in younger participants (ages 48–59), which converged in the oldest (age 80+). ANA positive women had higher odds of type 2 diabetes (OR: 2.06, 95% confidence interval: 1.04, 4.07) and multimorbidity (OR: 2.47, 95% confidence interval 1.11, 5.50) than women who were ANA negative. No statistically significant associations were observed in men. Insight into differences in age-related ANA positivity and ANA associations with chronic diseases by sex is important for understanding the impact of immune dysregulation in aging individuals. • Sex differences in ANA seropositivity at younger ages appeared to converge in the oldest individuals. • Women with multimorbidity have higher odds of ANA. • Understanding the contribution of ANA to morbidity may lend insight into healthy aging. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether regular use of nonsteroidal anti‐inflammatory drugs (NSAIDs) is associated with poor olfaction in older adults. Methods: We selected 4020 participants, aged 50 to 79 years in 2018, from 36,492 eligible participants in the National Institute of Environmental Health Sciences Sister Study, according to their self‐reported olfaction status. Of these, 3406 women completed the 12‐item Brief Smell Identification Test. We defined poor olfaction as a test score ≤9 in the primary analysis. We then estimated odds ratios (ORs) and 95% confidence intervals (CIs) from weighted logistic models, accounting for the study design, missing exposures/outcomes, and covariates. Results: Overall, NSAID use was not associated with poor olfaction. However, we found evidence for potential multiplicative interactions. Specifically, the OR comparing regular versus never use of aspirin was 1.8 (95% CI, 1.1–3.2) among women who had not regularly used nonaspirin NSAIDs, while the corresponding OR was 0.8 (95% CI, 0.5–1.2) among nonaspirin NSAID users (P for interaction = 0.016). Similar results were seen for ibuprofen alone versus ibuprofen with other NSAID use (P for interaction = 0.010). Among women using either drug alone, associations with poor olfaction increased with increasing duration and cumulative dose. Post hoc analyses showed that the interactions could not be readily explained by potential biases. Other NSAIDs were not associated with olfaction. Conclusion: Long‐term regular use of aspirin or ibuprofen was associated with poor olfaction among women who never regularly used other types of NSAIDs. These preliminary findings warrant independent confirmation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Some personal care products (PCPs) contain endocrine-disrupting chemicals that may affect breast cancer (BC) risk. Patterns of use vary by race and ethnicity. Use often starts in adolescence, when rapidly developing breast tissue may be more susceptible to environmental carcinogens. Few studies have examined associations of BC with PCP use during this susceptible window. OBJECTIVES: We characterized race and ethnicity-specific patterns of PCP use at 10-13 years of age and estimated associations of use with incident BC. METHODS: At enrollment (2003-2009), Sister Study participants (푛=4,049 Black, 2,104 Latina, and 39,312 White women) 35-74 years of age reported use of 37 "everyday" PCPs during the ages of 10-13 y (did not use, sometimes, or frequently used). We conducted race and ethnicity-specific latent class analyses to separately identify groups of women with similar patterns of beauty, hair, and skincare/hygiene product use. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for associations of identified PCP classes and single products with incident BC using Cox proportional hazards regression. RESULTS: During a mean follow-up time of 10.8 y, 280 Black, 128 Latina, and 3,137 White women were diagnosed with BC. Classes of adolescent PCP use were not clearly associated with BC diagnosis among Black, Latina, or White women. HRs were elevated but imprecise for frequent nail product and perfume use in Black women (HR=1.34; 95% CI: 0.85, 2.12) and greater hair product use in Black (HR=1.28; 95% CI: 0.91, 1.80) and Latina (HR =1.42; 95% CI: 0.81, 2.48) women compared with lighter use. In single-product models, we observed higher BC incidence associated with frequent use of lipstick, nail products, pomade, perfume, makeup remover, and acne/blemish products in at least one group. DISCUSSION: This work provides some support for the hypothesis that PCP use during puberty is associated with BC risk. More research is needed to confirm these novel findings. [ABSTRACT FROM AUTHOR]

Presents a study in which the `null' genotype of glutathione S-transferases theta 1 (GSTT1) and M1 (GSTM1) altered the risk for myelodyplastic syndromes (MDS). Explanation of MDS; Patients and methods; Findings; Results and discussion.

Background: Familial clustering of age at onset would have implications for both personalized screening and aetiology, but has not been studied for breast cancer.Methods: We prospectively studied a cohort of 23 145 sisters to explore whether their breast cancer risk changed near the age at diagnosis of a previously affected older sister. Using an age-time-dependent variable in a Cox regression model, we estimated hazard ratios for breast cancer when participants were near their sister's diagnosis age, relative to similarly aged women whose sister was diagnosed at a very different age. To rule out a correlation driven by young-onset familial cancer, we separately investigated women who had enrolled at age 50 or older.Results: Of the 23 145 women, 1412 developed breast cancer during follow-up (median 9.5 years). The estimated hazard ratio was 1.80 (95% confidence interval: 1.18, 2.74) at their sister's age at diagnosis, suggesting a substantial increase in risk compared with women of the same age but whose sister was diagnosed at a very different age. Restriction to women who enrolled at or after age 50 produced similar results.Conclusions: This familial clustering suggests that there may be important genetic and/or early environmental risk factors that influence the timing of breast cancer, even when onset is late in life. Personalized screening might need to account for the age at which a sister was earlier diagnosed with breast cancer. [ABSTRACT FROM AUTHOR]

To describe the geographic pattern of breast cancer incidence in a nationwide prospective cohort and investigate whether environmental exposures and/or neighborhood socioeconomic status explain observed geographic disparities. Using accelerated failure time models with a spatial random effect term, we mapped the health region-level association between residential location and breast cancer incidence for 44,707 participants in the Sister Study after controlling for established individual-level breast cancer risk factors. We performed a variable selection process to select environmental exposures [i.e., ambient nitrogen dioxide (NO 2) and fine particulate matter (PM 2.5), PM 2.5 chemical composition, outdoor light at night (LAN), ambient noise, ultraviolet radiation, and greenspace] and neighborhood-level factors [i.e., population density and area deprivation index (ADI)] that predicted breast cancer incidence and quantified the spatial variation explained by the selected factors. We also considered whether the geographic pattern and predictors were similar when restricting to estrogen receptor-positive (ER+) tumors. We observed a spatial patterning in the incidence of overall breast cancer (Moran's I = 16.7, p < 0.05) and ER+ breast cancer (Moran's I = 13.2, p < 0.05), with a lower risk observed in the South and Southeast and a greater risk in the Northwest and certain areas of the Midwest and Northeast. NO 2 , LAN, and ADI explained 21.4% of the spatial variation in overall breast cancer incidence whereas NO 2 , PM 2.5 chemical composition, LAN, greenspace, and ADI together explained 63.3% of the spatial variation in ER+ breast cancer incidence. Our findings provide additional evidence for a role of environmental exposures in breast cancer incidence and suggest that geographic-based risk factors may vary according to breast cancer subtype. Our findings support the need for additional research to quantify the relative contributions of geographic-based risk factors for breast cancer. [ABSTRACT FROM AUTHOR]

BACKGROUND: Air pollutants may contribute to the development of Parkinson's disease (PD), but empirical evidence is limited and inconsistent. OBJECTIVES: This study aimed to prospectively investigate the associations of PD with ambient exposures to fine particulate matter with aerodynamic diameter = 2.5μm (PM2.5) and nitrogen dioxide (NO2). METHODS: We analyzed data from 47,108 US women from the Sister Study, enrolled from 2003–2009 (35–80 years of age) and followed through 2018. Exposures of interest included address-level ambient PM2.5 and NO2 in 2009 and their cumulative averages from 2009 to PD diagnosis with varying lag-years. The primary outcome was PD diagnosis between 2009 and 2018 (푛 = 163). We used multivariable Cox proportional hazards and time-varying Cox models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: NO2 exposure in 2009 was associated with PD risk in a dose-response manner. The HR and 95% CI were 1.22 (95% CI: 1.03, 1.46) for one interquartile [4.8 parts per billion (ppb)] increment in NO2, adjusting for age, race and ethnicity, education, smoking status, alcohol drinking, caffeine intake, body mass index, physical activity, census region, residential area type, area deprivation index (ADI), and self-reported health status. The association was confirmed in secondary analyses with time-varying averaged cumulative exposures. For example, the multivariable adjusted HR for PD per 4.8 ppb increment in NO2 was 1.25 (95% CI: 1.05, 1.50) in the 2-year lag analysis using cumulative average exposure. Post hoc subgroup analyses overall confirmed the association. However, statistical interaction analyses found that the positive association of NO2 with PD risk was limited to women in urban, rural, and small town areas and women with = 50th percentile ADI but not among women from suburban areas or areas with < 50th percentile ADI. In contrast, PM2.5 exposure was not associated with PD risk with the possible exception for women from the Midwest region of the US (HRinterquartile-range = 2.49, 95% CI: 1.20, 5.14) but not in other census regions. DISCUSSION: In this nationwide cohort of US women, higher level exposure to ambient NO2 is associated with a greater risk of PD. This finding needs to be independently confirmed and the underlying mechanisms warrant further investigation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Glyphosate is the most commonly used herbicide worldwide and has been implicated in the development of certain hematologic cancers. Although mechanistic studies in human cells and animals support the genotoxic effects of glyphosate, evidence in human populations is scarce. OBJECTIVES: We evaluated the association between lifetime occupational glyphosate use and mosaic loss of chromosome Y (mLOY) as a marker of genotoxicity among male farmers. METHODS: We analyzed blood-derived DNA from 1,606 farmers ≥ 50 years of age in the Biomarkers of Exposure and Effect in Agriculture study, a subcohort of the Agricultural Health Study. mLOY was detected using genotyping array intensity data in the pseudoautosomal region of the sex chromosomes. Cumulative lifetime glyphosate use was assessed using self-reported pesticide exposure histories. Using multivariable logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between glyphosate use and any detectable mLOY (overall mLOY) or mLOY affecting ≥ 10% of cells (expanded mLOY). RESULTS: Overall, mLOY was detected in 21.4% of farmers, and 9.8% of all farmers had expanded mLOY. Increasing total lifetime days of glyphosate use was associated with expanded mLOY [highest vs. lowest quartile; OR = 1.75 (95% CI: 1.00, 3.07), 푝trend = 0.03] but not with overall mLOY; the associations with expanded mLOY were most apparent among older (≥ 70 years of age) men [OR = 2.30 (95% CI: 1.13, 4.67), 푝trend = 0.01], never smokers [OR = 2.32 (95% CI: 1.04, 5.21), 푝trend = 0.04], and nonobese men [OR = 2.04 (95% CI: 0.99, 4.19), 푝trend = 0.03]. Similar patterns of associations were observed for intensity-weighted lifetime days of glyphosate use. DISCUSSION: High lifetime glyphosate use could be associated with mLOY affecting a larger fraction of cells, suggesting glyphosate could confer genotoxic or selective effects relevant for clonal expansion. As the first study to investigate this association, our findings contribute novel evidence regarding the carcinogenic potential of glyphosate and require replication in future studies. [ABSTRACT FROM AUTHOR]

Background Breast cancer survivors have increased incidence of age-related diseases, suggesting that some survivors may experience faster biological aging. Methods Among 417 women enrolled in the prospective Sister Study cohort, DNA methylation data were generated on paired blood samples collected an average of 7.7 years apart and used to calculate 3 epigenetic metrics of biological aging (PhenoAgeAccel, GrimAgeAccel, and Dunedin Pace of Aging Calculated from the Epigenome [DunedinPACE]). Approximately half (n = 190) the women sampled were diagnosed and treated for breast cancer between blood draws, whereas the other half (n = 227) remained breast cancer–free. Breast tumor characteristics and treatment information were abstracted from medical records. Results Among women who developed breast cancer, diagnoses occurred an average of 3.5 years after the initial blood draw and 4 years before the second draw. After accounting for covariates and biological aging metrics measured at baseline, women diagnosed and treated for breast cancer had higher biological aging at the second blood draw than women who remained cancer-free as measured by PhenoAgeAccel (standardized mean difference [β] = 0.13, 95% confidence interval [CI) = 0.00 to 0.26), GrimAgeAccel (β = 0.14, 95% CI = 0.03 to 0.25), and DunedinPACE (β = 0.37, 95% CI = 0.24 to 0.50). In case-only analyses assessing associations with different breast cancer therapies, radiation had strong positive associations with biological aging (PhenoAgeAccel: β = 0.39, 95% CI = 0.19 to 0.59; GrimAgeAccel: β = 0.29, 95% CI = 0.10 to 0.47; DunedinPACE: β = 0.25, 95% CI = 0.02 to 0.48). Conclusions Biological aging is accelerated following a breast cancer diagnosis and treatment. Breast cancer treatment modalities appear to differentially contribute to biological aging. [ABSTRACT FROM AUTHOR]

Background: As breast cancer represents a major morbidity and mortality burden in the U.S., with about one in eight women developing invasive breast cancer over her lifetime, accurate low-cost screening is an important public health issue. First-degree family history, often simplified as a dichotomous or three-level categorical variable (0/1/>1) based on number of affected relatives, is an important risk factor for many conditions. However, detailed family structure information such as the total number of first-degree relatives, and for each, their current or death age, and age at diagnosis are also important for risk prediction. Methods: We develop a family history score under a Bayesian framework, based on first-degree family structure. We tested performance of the proposed score using data from a large prospective cohort study of women with a first-degree breast cancer family history. We used likelihood ratio tests to evaluate whether the proposed score added additional information to a Cox model with known breast cancer risk factors and the three-level family history variable. We also compared prediction performance through Receiver Operating Characteristic (ROC) curves and goodness-of-fit testing. Results: Our proposed Bayesian family history score improved fit compared to the commonly used three-level family history score, both without and with adjustment for other risk factors (likelihood ratio tests p = 0.003 without adjustment for other risk factors, and p = 0.007 and 0.009 under adjustment with two candidate sets of risk factors). AUCs of ROC curves for the two models were similar, though in all cases were higher after addition of the BFHS. Conclusions: Capturing detailed family history data through the proposed family history score can improve risk assessment and prediction. Such approaches could enable better-targeted personalized screening schedules and prevention strategies. [ABSTRACT FROM AUTHOR]

We investigated the role of socioeconomic disparities in the association between diet and risk of type 2 diabetes (T2D). We used prospective data from 40,243 Sister Study participants aged 35 to 74 years who were enrolled in 2003–2009. Scores for healthy eating indices (alternate Mediterranean diet, Dietary Approaches to Stop Hypertension, alternative Healthy Eating Index, and Healthy Eating Index 2015 (HEI-2015)) were calculated using data from a 110-item food frequency questionnaire completed at enrollment. Incident T2D was defined based on self-reported physician's diagnosis or use of anti-diabetic medications. Multivariable-adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. We observed inverse associations between all four dietary indices and incident T2D after multivariable adjustment. These associations were most pronounced among women with higher educational attainment, higher income, and lower area deprivation index (ADI) (e.g., for the HEI-2015: low ADI, aHR Q4vsQ1 : 0.44, 95% CI: 0.35, 0.56 vs high ADI, aHR Q4vsQ1 : 0.75, 95% CI: 0.63, 0.90; p interaction : 0.0007). Weaker associations among women with lower socioeconomic status and higher neighborhood deprivation suggests that other factors play a larger role in T2D incidence than diet quality among individuals with low SES. [ABSTRACT FROM AUTHOR]

BACKGROUND: Improving mental health is recognized as an important factor for achieving global development goals. Despite strong evidence that neighborhood greenery promotes better mental health, there are environmental justice concerns over the distribution of neighborhood greenery. Underlying these concerns are present-day consequences of historical discriminatory financial investment practices, such as redlining which was established by the U.S. Federal Home Owners’ Loan Corporation (HOLC) in the 1930s. The impacts of redlining on environmental and health disparities have been researched extensively. However, the influences of redlining on the associations between neighborhood environment and health outcomes have not been fully assessed. OBJECTIVES: The aim of this study was to examine whether associations between residential tree cover and depressive symptoms vary across areas subject to HOLC practices. METHODS: Depressive symptoms were defined by the 10-item Center for Epidemiologic Studies Depression Scale collected during the period 2008– 2012 for 3,555 women in the Sister Study cohort residing in cities subject to HOLC practices across the United States. HOLC rating maps were obtained from the Mapping Inequality Project, University of Richmond, with neighborhoods graded as A (best for financial investment, green), B (still desirable, blue), C (declining, yellow), and D (hazardous, red—known as redlined). Tree cover within 500 m and 2,000 m from residences was estimated using 2011 U.S. Forest Service Percent Tree Canopy Cover. Mixed model using climate zone as the random effect was applied to evaluate the associations with adjustments for potential covariates. Analyses were stratified by HOLC grade. RESULTS: Tree cover was significantly higher in neighborhoods with better HOLC grades. A 10% increase in tree cover was associated with reduced odds of depressive symptoms for the full study population, with adjusted odds ratios (AORs) of 0.93 [95% confidence interval (CI): 0.88, 0.99], and 0.91 (0.85, 0.97) for 500-m and 2,000-m buffer, respectively. Across HOLC grades, the strongest associations were observed in redlined neighborhoods, with respective AORs of 0.72 (95% CI: 0.52, 0.99) and 0.63 (95% CI: 0.45, 0.90) for 500-m and 2,000-m buffer. DISCUSSION: Findings support a remediation strategy focused on neighborhood greenery that would address multiple public health priorities, including mental health and environmental justice. [ABSTRACT FROM AUTHOR]

BACKGROUND: Poor olfaction is common in older adults and may have profound adverse implications on their health. However, little is known about the potential environmental contributors to poor olfaction. OBJECTIVE: We investigated ambient fine particulate matter [PM ≤ 2.5 μm in aerodynamic diameter (PM2.5)] and nitrogen dioxide (NO2) in relation to poor olfaction in middle-aged to older women. METHODS: The Sister Study is a nationwide cohort of 50,884 women in the United States with annual average air pollutant exposures estimated based on participants' residences from enrollment (2003-2009) through 2017. This analysis was limited to 3,345 women, 50-79 years of age as of January 2018, who completed the Brief Smell Identification Test (B-SIT) in 2018-2019. Poor olfaction was defined as a B-SIT score of ≤ 9 in the primary analysis. We conducted multivariable logistic regressions, accounting for covariates and study sampling design. RESULTS: Overall, we found little evidence for associations of air pollutants with poor olfaction. The odds ratio (OR) and 95% confidence interval (CI) of poor olfaction for each interquartile range (IQR) increment of air pollutants in 2006 were 1.03 (95% CI: 0.91, 1.17) for PM2.5 (per 3.3 μg/m³) and 1.08 (95% CI: 0.96, 1.22) for NO2 (per 5.7 ppb). Results were similar in the analyses using the most recent (2017) or the cumulative average (2006-2017) air pollutant exposure data. Secondary analyses suggested potential association in certain subgroups. The OR per IQR was 1.35 (95% CI: 1.11, 1.65) for PM2.5 among younger participants (< 54.2 years of age) and 1.87 (95% CI: 1.29, 2.71) for NO2 among current smokers. DISCUSSION: This study did not find convincing evidence that air pollutants have lasting detrimental effects on the sense of smell of women 50-79 years of age. The subgroup analyses are exploratory, and the findings need independent confirmation. [ABSTRACT FROM AUTHOR]

Background/Objectives: Antibiotic use in early life has been associated with weight gain in several populations. However, associations between chronic antibiotic use and weight among adults in the general population are unknown. Subjects/Methods: The NIEHS Sister Study is a longitudinal cohort of sisters of women with breast cancer. We examined associations between chronic antibiotic use (≥ 3 months) during the fourth decade of life (30–39 years) and subsequent obesity at enrollment (mean age = 55) via logistic regression. We also examined associations between chronic antibiotic use in the 5 years and 12 months prior to enrollment and weight gain after enrollment in linear mixed models. Models were adjusted for race/ethnicity, education, urban/rural status, age, and smoking. Results: In adjusted analyses (n = 50,237), chronic penicillin use during the 4th decade of life was associated with obesity at enrollment (OR 2.00, 95% CI 1.40, 2.87), and use in the 5 years prior to enrollment was associated with increased BMI change after enrollment (β 1.00 95% CI 0.01, 2.00). Use of bactericidals (OR 1.71, 95% CI 1.29, 2.26) during the 4th decade of life was also associated with obesity at enrollment. Associations for penicillins and bactericidals were consistent across indications for use. Bacteriostatic use in the 5 years prior to enrollment was associated with a reduction in BMI after enrollment (β -0.52, 95% CI -1.04, 0.00), and tetracycline use during the 4th decade of life was associated with reduced odds of obesity at enrollment (OR 0.72, 95% CI 0.56, 0.92). However, these inverse associations were only present for those who reported taking antibiotics for skin purposes. Cephalosporins, macrolides, quinolones, and sulfonamides were not associated with BMI change over time. Conclusions: Chronic use of antibiotics during adulthood may have long-lasting impacts on BMI. Associations may differ by antibiotic class, and confounding by indication may be important for some antibiotic classes. [ABSTRACT FROM AUTHOR]

Background: Large prospective studies are essential for investigating the environmental causes of Parkinson's disease (PD), but PD diagnosis via clinical exams is often infeasible in such studies. Objective: To present case ascertainment strategy and data collection in a US cohort of women. Methods: In the Sister Study (n = 50,884, baseline ages 55.6±9.0), physician-made PD diagnoses were first reported by participants or their proxies. Cohort-wide follow-up surveys collected data on subsequent diagnoses, medication usage and PD-relevant motor and nonmotor symptoms. We contacted self-reported PD cases and their treating physicians to obtain relevant diagnostic and treatment history. Diagnostic adjudication was made via expert review of all available data, except nonmotor symptoms. We examined associations of nonmotor symptoms with incident PD, using multivariable logistic regression models and reported odds ratio (OR) and 95% confidence intervals (CI). Results: Of the 371 potential PD cases identified, 242 diagnoses were confirmed. Compared with unconfirmed cases, confirmed cases were more likely to report PD diagnosis from multiple sources, medication usage, and motor and nonmotor features consistently during the follow-up. PD polygenic risk score was associated with confirmed PD (ORinter-quartile range = 1.74, 95% CI: 1.45–2.10), but not with unconfirmed cases (corresponding OR = 1.05). Hyposmia, dream-enacting behaviors, constipation, depression, unexplained weight loss, dry eyes, dry mouth, and fatigue were significantly related to PD risk, with ORs from 1.71 to 4.88. Only one of the eight negative control symptoms was associated with incident PD. Conclusion: Findings support our PD case ascertainment approach in this large cohort of women. PD prodromal presentation is likely beyond its well-documented profile. [ABSTRACT FROM AUTHOR]