Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 365
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Hum Reprod ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31600381

RESUMO

STUDY QUESTION: Are reproductive characteristics associated with genome-wide DNA methylation and epigenetic age? SUMMARY ANSWER: Our data suggest that increasing parity is associated with differences in blood DNA methylation and small increases in epigenetic age. WHAT IS KNOWN ALREADY: A study of 397 young Filipino women (ages 20-22) observed increasing epigenetic age with an increasing number of pregnancies. STUDY DESIGN, SIZE, DURATION: We used data from 2356 non-Hispanic white women (ages 35-74) enrolled in the Sister Study cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data on reproductive history were ascertained via questionnaire. Of the 2356 women, 1897 (81%) reported at least one live birth. Among parous women, 487 (26%) women reported ever experiencing a pregnancy complication. Three epigenetic clocks (i.e. Hannum, Horvath and Levine) and genome-wide methylation were measured in DNA from whole blood using Illumina's HumanMethylation450 BeadChip. We estimated association ß-values and 95% CIs using linear regression. MAIN RESULTS AND THE ROLE OF CHANCE: All three epigenetic clocks showed weak associations between number of births and epigenetic age (per live birth; Hannum: ß = 0.16, 95% CI = 0.02, 0.29, P = 0.03; Horvath: ß = 0.12, 95% CI = -0.04, 0.27, P = 0.14; Levine: ß = 0.27, 95% CI = 0.08, 0.45, P = 0.01); however, additional adjustment for current BMI attenuated the associations. Among parous women, a history of abnormal glucose tolerance during pregnancy was associated with increased epigenetic age by the Hannum clock (ß = 0.96; 95% CI = 0.10, 1.81; P = 0.03) and Levine clocks (ß = 1.69; 95% CI = 0.54, 2.84; P < 0.01). In epigenome-wide analysis, increasing parity was associated with methylation differences at 17 CpG sites (Bonferroni corrected P≤ 1.0 × 10-7). LIMITATIONS, REASONS FOR CAUTION: We relied on retrospective recall to ascertain reproductive history and pregnancy complications. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that parity is associated with small increases in epigenetic age and with DNA methylation at multiple sites in the genome. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the Intramural Research program of the NIH, National Institute of Environmental Health Sciences (Z01-ES049033, Z01-ES049032 and Z01-ES044055). None of the authors have a conflict of interest. TRIAL REGISTRATION NUMBER: Not applicable.

2.
Environ Health Perspect ; 127(10): 107002, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31596602

RESUMO

BACKGROUND: Particulate matter (PM) is a complex mixture. Geographic variations in PM may explain the lack of consistent associations with breast cancer. OBJECTIVE: We aimed to evaluate the relationship between air pollution, PM components, and breast cancer risk in a United States-wide prospective cohort. METHODS: We estimated annual average ambient residential levels of particulate matter <2.5 µm and <10 µm in aerodynamic diameter (PM2.5 and PM10, respectively) and nitrogen dioxide (NO2) 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 k-means were used to assign participants to clusters derived from PM2.5 component profiles to evaluate the impact of heterogeneity in the PM2.5 mixture. For PM2.5, we investigated effect measure modification by component cluster membership and by geographic region without regard to air pollution mixture. RESULTS: During follow-up (mean=8.4 y), 2,225 invasive and 623 ductal carcinoma in situ (DCIS) cases were identified. PM2.5 and NO2 were associated with breast cancer overall [HR=1.05 (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 PM2.5 only in the Western United States [HR=1.14 (95% CI:1.02, 1.27)] and NO2 only in the Southern United States [HR=1.16 (95% CI:1.01, 1.33)]. PM2.5 was associated with a higher risk of invasive breast cancer among two of seven identified composition-based clusters. A higher risk was observed [HR=1.25 (95% CI: 0.97, 1.60)] in a California-based cluster characterized by low S and high Na and nitrate (NO3-) fractions and for another Western United States cluster [HR=1.60 (95% CI: 0.90, 2.85)], characterized by high fractions of Si, Ca, K, and Al. CONCLUSION: 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.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31575555

RESUMO

BACKGROUND: Red and processed meats have been implicated as risk factors in the development of colorectal cancer (CRC) in U.S. women, but associations with cooking practices are less well established. METHODS: Data are from the Sister Study, a cohort of women 35-74 years old from U.S. and Puerto Rico who have a sister diagnosed with breast cancer. Red and processed meat consumption, meat cooking practices, and intake of common meat products were collected at baseline using self-administered questionnaires (N=48,704). Multivariable hazard ratios (HRadj) and 95% confidence intervals (95%CIs) were estimated. RESULTS: During a median 8.7 years follow-up (range <1-12.7 years), 216 CRC cases were diagnosed. In categorical analyses, an increased risk of CRC was seen in the highest quartile of processed meat consumption compared to the lowest [HRadj=1.52 (95%CI: 1.01-2.30); p-trend: 0.02], and for specific meat products, including breakfast sausages (HRadj=1.85 [95%CI: 1.30-2.64]) and bacon (HRadj=1.46 [95%CI: 1.01-2.11]). The adjusted HR for the highest quartile of red meat consumption was 1.04 (95%CI: 0.68-1.60), and little evidence of association was observed for cooking practices or doneness of red meat. We observed positive associations with specific red meat products when cooking methods were considered; e.g., grilled/ barbequed steaks (HRadj=2.23 [95%CI: 1.20-4.14]) and hamburgers (HRadj=1.98 [95%CI: 1.00-3.91]). CONCLUSIONS: Higher reported daily intake of processed meats and consumption of barbecued/grilled red meat products were associated with increased risk of CRC in women. IMPACT: Variability in CRC risk by meat type and cooking method should be considered when evaluating meat consumption.

4.
Epidemiology ; 30(6): 845-852, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31584892

RESUMO

BACKGROUND: Perineal talc use and douching could affect the risk of uterine cancer through several possible pathways, including inflammation response, microbiota changes, or endocrine disruption. Two previous cohort studies of the association between talc use and uterine cancer have reported weak positive associations, but we know of no previous evaluations of the relationship between douching and uterine cancer. METHODS: Using a large prospective cohort, we examined the relationship between incident uterine cancer and self-reported use of talc or douche using Cox proportional hazards models. RESULTS: After excluding those with prior hysterectomy, 271 of 33,609 women reported incident uterine cancer (mean follow-up = 8.3 years in noncases; maximum 12.6 years). Overall, 26% of women reported ever using talc and 15% reported ever having douched. Ever talc use was associated with an increase in risk of uterine cancer (adjusted hazard ratio [HR] = 1.2; 95% confidence interval [CI] = 0.94, 1.6), with some evidence of a dose-response for frequency of talc use (P-for-trend = 0.07). Ever douching was not associated with uterine cancer risk (HR = 1.0; 95% CI = 0.72, 1.5), with no evidence of a frequency dose-response (P = 0.96). The estimates were similar when we restricted to invasive endometrial cancers, but not when we further restricted to endometroid adenocarcinomas. CONCLUSION: The positive association we observed between talc use and uterine cancer risk is consistent with findings from previous prospective cohort studies of endometrial cancer. The relationships between uterine cancer and both douching and talc use merit further consideration, particularly as both exposures are preventable.

5.
Int J Cancer ; 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31389007

RESUMO

Meat consumption has been postulated to increase the risk of breast cancer, but this association has not been consistently seen. We examined the association between consumption of different types of meat, meat mutagens and incident invasive breast cancer. Information on consumption of different meat categories and meat cooking practice behaviors was obtained from 42,012 Sister Study participants who completed a Block 1998 Food Frequency Questionnaire at enrollment (2003-2009) and satisfied eligibility criteria. Exposure to meat type and meat mutagens was calculated, and associations with invasive breast cancer risk were estimated using multivariable Cox proportional hazards regression. During follow-up (mean, 7.6 years), 1,536 invasive breast cancers were diagnosed at least 1 year after enrollment. Increasing consumption of red meat was associated with increased risk of invasive breast cancer (HRhighest vs. lowest quartile :1.23, 95% CI: 1.02-1.48, ptrend = 0.01). Conversely, increasing consumption of poultry was associated with decreased invasive breast cancer risk (HR highest vs. lowest quartile : 0.85; 95% CI: 0.72-1.00; ptrend = 0.03). In a substitution model with combined red meat and poultry consumption held constant, substituting poultry for red meat was associated with decreased invasive breast cancer risk (HR highest vs. lowest quartile of poultry consumption: 0.72, 95% CI: 0.58-0.89). No associations were observed for cooking practices, estimated heterocyclic amines or heme iron from red meat consumption with breast cancer risk. Red meat consumption may increase the risk of invasive breast cancer, whereas poultry consumption may be associated with reduced risk. Substituting poultry for red meat could reduce breast cancer risk.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31431499

RESUMO

Tamoxifen and raloxifene have been approved for the primary prevention of breast cancer in high-risk women, but are associated with an increased risk of serious side effects. Few studies have characterized risk-benefit profiles for chemoprevention among women who initiate tamoxifen or raloxifene outside of a clinical trial setting. Use of raloxifene and tamoxifen for chemoprevention was self-reported in 2014-2016 by participants in The Sister Study, a prospective cohort of women with a sister who had been diagnosed with breast cancer. After exclusions, 432 current raloxifene users and 96 current tamoxifen users were matched to 4307 and 953 non-users, respectively, on age and year of cohort enrollment. Conditional logistic regression was used to evaluate characteristics associated with chemoprevention use. Risk-benefit profiles were examined using published indices that assess the level of evidence (none, moderate, strong) that the benefits of chemoprevention outweigh the risk of serious side effects. Among current chemoprevention users, 44% of tamoxifen users and 5% of raloxifene users had no evidence of a net benefit. In analyses of factors associated with chemoprevention use, having strong evidence of benefit was a significant predictor of raloxifene use, but not of tamoxifen use. In our sample of women with a first-degree family history of breast cancer, raloxifene was more commonly used for breast cancer prevention than tamoxifen. Most raloxifene users, but <60% of tamoxifen users, were likely to benefit. Use of risk-benefit tables can help women and their healthcare providers make an informed decision about breast cancer chemoprevention.

7.
Occup Environ Med ; 76(9): 632-643, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31413186

RESUMO

OBJECTIVES: Lower mortality rates compared with the general population have been reported for Agricultural Health Study (AHS) participants (enrolled 1993-1997) followed through 2007. We extended analysis of mortality among AHS participants (51 502 private pesticide applicators, their 31 867 spouses and 4677 commercial pesticide applicators from North Carolina and Iowa) through 2015 and compared results using several analytical approaches. METHODS: We calculated standardised mortality ratios (SMRs), causal mortality ratios (CMR) and relative SMRs (rSMR) using state-specific mortality rates of the general populations as the referent. RESULTS: Over the average 16 years of follow-up (1999-2015), 9305 private applicators, 3384 spouses and 415 commercial applicators died. SMRs and CMRs, with expected deaths calculated using the person-time among the cohort and the general population, respectively, indicated lower overall mortality in all study subgroups (SMRs from 0.61 to 0.69 and CMRs from 0.74 to 0.89), although CMRs indicated elevated mortality in private applicators from North Carolina and in ever-smokers. In SMR analyses, there were fewer than expected deaths from many causes, but deaths from some external causes including transportation-related injuries and mechanical forces were elevated in private applicators. CMRs indicated higher than expected deaths from prostate cancer, lymphohaematopoietic cancers, Parkinson's and Alzheimer's disease, and chronic glomerulonephritis in private applicators, and non-Hodgkin's lymphoma in spouses (from 1.19 to 1.53). rSMR results were generally elevated, similar to CMR findings. CONCLUSIONS: AHS participants experienced lower overall mortality than the general population.Mortality from a few specific causes was increased in private applicators, specifically when CMR and rSMR approaches were used.

8.
Curr Environ Health Rep ; 6(3): 174-187, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31376082

RESUMO

Research conducted in the wake of a disaster can provide information to help mitigate health consequences, support future recovery efforts, and improve resilience. However, a number of barriers have prevented time-sensitive research responses following previous disasters. Furthermore, large-scale disasters present their own special challenges due to the number of people exposed to disaster conditions, the number of groups engaged in disaster response, and the logistical challenges of rapidly planning and implementing a large study. In this case study, we illustrate the challenges in planning and conducting a large-scale post-disaster research study by drawing on our experience in establishing the Gulf Long-term Follow-up (GuLF) Study following the 2010 Deepwater Horizon disaster. We describe considerations in identifying at-risk populations and appropriate comparison groups, garnering support for the study from different stakeholders, obtaining timely scientific and ethics review, measuring and characterizing complex exposures, and addressing evolving community health concerns and unmet medical needs. We also describe the NIH Disaster Research Response (DR2) Program, which provides a suite of resources, including data collection tools, research protocols, institutional review board guidance, and training materials to enable the development and implementation of time-critical studies following disasters and public health emergencies. In describing our experiences related to the GuLF Study and the ongoing efforts through the NIH DR2 Program, we aim to help improve the timeliness, quality, and value of future disaster-related data collection and research studies.

9.
Environ Int ; 132: 105071, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31387022

RESUMO

BACKGROUND: Epigenetic age, as defined by DNA methylation, may be influenced by air pollution exposure. OBJECTIVE: To evaluate the relationship between NO2, particulate matter (PM), PM components and accelerated epigenetic age. METHODS: In a sample of non-Hispanic white women living in the contiguous U.S. (n = 2747), we estimated residential exposure to PM2.5, PM10 and NO2 using a model incorporating land-use regression and kriging. Predictive k-means was used to assign participants to clusters representing different PM2.5 component profiles. We measured DNA methylation (DNAm) in blood using the Illumina's Infinium HumanMethylation450 BeadChip and calculated DNAm age using the Hannum, Horvath and Levine epigenetic clocks. Age acceleration was defined based on residuals after regressing DNAm age on chronological age. We estimated associations between interquartile range (IQR) increases in pollutants and age acceleration using linear regression. For PM2.5, we stratified by cluster membership. We examined epigenome-wide associations using robust linear regression models corrected with false discovery rate q-values. RESULTS: NO2 was inversely associated with age acceleration using the Hannum clock (ß = -0.24, 95% CI: -0.47, -0.02). No associations were observed for PM10. For PM2.5, the association with age acceleration varied by PM2.5 component cluster. For example, with the Levine clock, an IQR increase in PM2.5 was associated with an over 6-year age acceleration in a cluster that has relatively high fractions of crustal elements relative to overall PM2.5 (ß = 6.57, 95% CI: 2.68, 10.47), and an almost 2-year acceleration in a cluster characterized by relatively low sulfur fractions (ß = 1.88, 95% CI: 0.51, 3.25). In a cluster distinguished by lower relative nitrate concentrations, PM2.5 was inversely associated with age acceleration (ß = -1.33, 95% CI: -2.43, -0.23). Across the epigenome, NO2 was associated with methylation at 2 CpG sites. CONCLUSION: Air pollution was associated with epigenetic age, a marker of mortality and disease risk, among certain PM2.5 component profiles.

10.
Front Immunol ; 10: 1476, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354699

RESUMO

Farming and pesticide use have been associated with systemic autoimmune diseases, and while certain organochlorine insecticides and other pesticides are suspected to influence risk, the role of specific pesticides in the development of systemic autoimmunity is not known. We measured serum antinuclear autoantibodies (ANA) by immunofluorescence on Hep-2 cells in 668 male farmers in the study of Biomarkers of Exposure and Effect in Agriculture (BEEA; 2010-2013), an Agricultural Health Study (AHS) subcohort. We examined ANA in relation to lifetime use of 46 pesticides first reported at AHS enrollment (1993-1997) and updated at intervals through BEEA enrollment. Odds ratios (OR) and 95% confidence intervals (CI) were estimated after adjusting for age, state, education, season of blood draw, current pesticide use, and correlated pesticides. Having ANA antibodies (3 or 4+ intensity at a 1:80 dilution, 21% of study participants) was associated with a reported history of seeking medical care due to exposure to pesticides (OR 2.15; 95%CI 1.17, 3.95), use of the fumigant methyl bromide (OR 3.16; 95%CI 1.05, 9.5), and use of petroleum oil/distillates (OR 1.50; 95%CI 1.00, 2.25). Using a higher threshold (3 or 4+ at a 1:160 dilution, 9%) ANA positivity was associated with the carbamate insecticide aldicarb (OR 4.82; 95%CI 1.33, 17.5) and greater combined use of four cyclodiene organochlorine insecticides (top tertile of intensity-weighted lifetime days vs. no use; OR T3 3.20; 95%CI 1.10, 9.27). By contrast, greater use of non-cyclodiene organochlorine insecticides was inversely associated with ANA (1:80 dilution 3 or 4+, OR T3 0.24; 95%CI 0.08, 0.72). Specific autoantibodies (to extractable nuclear antigens and anti-dsDNA), measured on those with ANA detected at the 1:80 dilution 3 or 4+, were seen in 15 individuals (2%), and were associated with use of two or more cyclodiene organochlorine insecticides and several other pesticides (e.g., carbofuran, ethylene dibromide). These findings suggest that specific pesticide exposures may have long-term effects on ANA prevalence and support the hypothesis that certain organochlorine insecticides may increase the risk of developing systemic autoimmunity.

11.
J Autoimmun ; : 102295, 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31303354

RESUMO

Age-associated increases in antinuclear antibodies (ANA) in the general population are commonly noted but the mechanisms underlying this observation are unclear. This study aims to evaluate whether shorter peripheral blood mononuclear cell (PBMC) telomere length, a marker of more advanced biological age, is associated with ANA positivity prevalence and incidence in middle and older aged autoimmune disease-free individuals from the Baltimore Longitudinal Study of Aging (BLSA). Telomere length was measured by Southern Blot and categorized into tertiles. ANA was measured in a 1:80 and a 1:160 dilution of sera by immunofluorescence using HEp-2 cells (seropositive = 3 or 4). Multiple logistic regression was used to estimate the odds ratios and 95% confidence intervals of ANA positivity comparing the shorter tertiles of telomere length to the longest tertile for two cross-sectional points in time and then longitudinally to assess the association between shorter telomere length and incident ANA positivity. Cross-sectional analyses were adjusted for sex, race and BMI (N = 368 baseline, N = 370 follow-up) and longitudinal analyses were adjusted for sex, race, BMI and time between baseline and follow-up (N = 246). No statistically significant cross-sectional associations were observed at baseline or follow-up. Among those where ANA negative at baseline, individuals with shorter telomeres were more likely to be ANA positive at follow-up, an average 13 years later. Individuals with short telomeres at both time periods were more likely to be ANA positive. Findings suggest that ANA positivity in the general population may be indicative of immune dysfunction resulting from advanced cellular aging processes.

12.
Sleep ; 42(8)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31260523

RESUMO

STUDY OBJECTIVES: Exposure to traumatic childhood experiences (TCEs) may contribute to poor sleep in adulthood. Previous studies have been limited to mainly investigating physical and sexual abuse and did not consider betrayal trauma, or whether the victim regarded the perpetrator as someone socially close to them, the age group at occurrence, and trauma-related distress/anxiety. METHODS: We used a large cohort of US women, 35-74 years old, enrolled in the Sister Study from 2003 to 2009. Self-reports of specific TCEs occurring before the age of 18 years included sexual, physical, and psychological/emotional trauma; natural disasters; major accidents; and household dysfunction. Participants self-reported average sleep duration (short: <7 hours vs recommended: 7-9 hours), sleep onset latency (SOL) at least 30 vs less than 30 minutes, at least 3 night awakenings once asleep at least 3 times/week (Night awakenings [NA], yes vs no), and napping at least 3 vs less than 3 times/week. RESULTS: Among 40 082 women, 55% reported a TCE, with 82% reporting betrayal trauma. Compared to women reporting no TCE, women with any TCE were more likely to report short sleep (prevalence ratio [PR] = 1.08, [95% confidence interval (CI) = 1.04 to 1.11]), longer SOL (1.11, [1.06 to 1.16]), frequent NAs (1.06, [1.00 to 1.11]), and frequent napping (1.05, [0.99 to 1.12]). The relationship between experiencing any TCE and short sleep was stronger for TCEs by a perpetrator considered socially close vs not close (1.12, [1.09 to 1.16]), SOL (1.27, [1.22 to 1.33]), NA (1.20, [1.14 to 1.27]), and napping (1.24, [1.17 to 1.32]). CONCLUSIONS: TCEs were associated with poor sleep in women with greater impact when the perpetrator was regarded as close. More research is warranted to better understand pathways between childhood trauma and sleep health in adulthood to develop effective interventions.

13.
Ann Work Expo Health ; 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31334553

RESUMO

Tens of thousands of individuals performed oil spill response and clean-up (OSRC) activities following the 'Deepwater Horizon' oil drilling rig explosion in 2010. Many were exposed to oil residues and dispersants. The US National Institute of Environmental Health Sciences assembled a cohort of nearly 33 000 workers to investigate potential adverse health effects of oil spill exposures. Estimates of dermal and inhalation exposure are required for those individuals. Ambient breathing-zone measurements taken at the time of the spill were used to estimate inhalation exposures for participants in the GuLF STUDY (Gulf Long-term Follow-up Study), but no dermal measurements were collected. Consequently, a modelling approach was used to estimate dermal exposures. We sought to modify DREAM (DeRmal Exposure Assessment Method) to optimize the model for assessing exposure to various oil spill-related substances and to incorporate advances in dermal exposure research. Each DREAM parameter was reviewed in the context of literature published since 2000 and modified where appropriate. To reflect the environment in which the OSRC work took place, the model treatment of evaporation was expanded to include vapour pressure and wind speed, and the effect of seawater on exposure was added. The modified model is called GuLF DREAM and exposure is estimated in GuLF DREAM units (GDU). An external validation to assess the performance of the model for oils, tars, and fuels was conducted using available published dermal wipe measurements of heavy fuel oil (HFO) and dermal hand wash measurements of asphalt. Overall, measured exposures had moderate correlations with GDU estimates (r = 0.59) with specific correlations of -0.48 for HFO and 0.68 for asphalt. The GuLF DREAM model described in this article has been used to generate dermal exposure estimates for the GuLF STUDY. Many of the updates made were generic, so the updated model may be useful for other dermal exposure scenarios.

14.
Environ Int ; 130: 104897, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31226564

RESUMO

INTRODUCTION: Potentially carcinogenic hazardous air pollutants (air toxics) have been inconsistently associated with breast cancer. Whether metabolic factors modify these associations is unknown. We studied 29 non-metallic air toxics classified as mammary gland carcinogens in animal studies in relation to breast cancer risk. METHODS: Participants included 49,718 women from the Sister Study. Census tract air toxic concentration estimates from the 2005 National Air Toxics Assessment were linked to enrollment residential addresses. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for individual air toxics were estimated using Cox regression. Body mass index (BMI) was considered a potential modifier. Relevant mixtures were identified using classification trees. RESULTS: Over follow-up (average = 8.4 years), 2975 women were newly diagnosed with breast cancer (invasive or ductal carcinoma in situ). Several air toxics, including methylene chloride, polycyclic organic matter, propylene dichloride, and styrene, were associated with increased risk. Of these, methylene chloride was most consistently associated with risk across multiple analyses. It was associated with overall (HRquintile 4vs1 = 1.21 (95%CI = 1.07-1.38)) and estrogen receptor positive (ER+) invasive breast cancer (HRquintile 4vs1 = 1.28 (95%CI = 1.08-1.52)) in individual pollutant models, although no dose-response was observed. Associations were stronger among overweight/obese (vs. non-overweight/obese) women (p < 0.05) for six air toxics. The classification tree identified combinations of age, methylene chloride, BMI, and four other toxics (propylene dichloride, ethylene dibromide, ethylidene dichloride, styrene) related to overall breast cancer. CONCLUSIONS: Some non-metallic air toxics, particularly methylene chloride, were associated with the hazard for overall and ER+ breast cancer. Overweight/obese women may be particularly susceptible to air toxics.

15.
JAMA Intern Med ; 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31180469

RESUMO

Importance: Short sleep has been associated with obesity, but to date the association between exposure to artificial light at night (ALAN) while sleeping and obesity is unknown. Objective: To determine whether ALAN exposure while sleeping is associated with the prevalence and risk of obesity. Design, Setting, and Participants: This baseline and prospective analysis included women aged 35 to 74 years enrolled in the Sister Study in all 50 US states and Puerto Rico from July 2003 through March 2009. Follow-up was completed on August 14, 2015. A total of 43 722 women with no history of cancer or cardiovascular disease who were not shift workers, daytime sleepers, or pregnant at baseline were included in the analysis. Data were analyzed from September 1, 2017, through December 31, 2018. Exposures: Artificial light at night while sleeping reported at enrollment, categorized as no light, small nightlight in the room, light outside the room, and light or television in the room. Main Outcomes and Measures: Prevalent obesity at baseline was based on measured general obesity (body mass index [BMI] ≥30.0) and central obesity (waist circumference [WC] ≥88 cm, waist-to-hip ratio [WHR] ≥0.85, or waist-to-height ratio [WHtR]≥0.5). To evaluate incident overweight and obesity, self-reported BMI at enrollment was compared with self-reported BMI at follow-up (mean [SD] follow-up, 5.7 [1.0] years). Generalized log-linear models with robust error variance were used to estimate multivariable-adjusted prevalence ratios (PRs) and relative risks (RRs) with 95% CIs for prevalent and incident obesity. Results: Among the population of 43 722 women (mean [SD] age, 55.4 [8.9] years), having any ALAN exposure while sleeping was positively associated with a higher prevalence of obesity at baseline, as measured using BMI (PR, 1.03; 95% CI, 1.02-1.03), WC (PR, 1.12; 95% CI, 1.09-1.16), WHR (PR, 1.04; 95% CI, 1.00-1.08), and WHtR (PR, 1.07; 95% CI, 1.04-1.09), after adjusting for confounding factors, with P < .001 for trend for each measure. Having any ALAN exposure while sleeping was also associated with incident obesity (RR, 1.19; 95% CI, 1.06-1.34). Compared with no ALAN, sleeping with a television or a light on in the room was associated with gaining 5 kg or more (RR, 1.17; 95% CI, 1.08-1.27; P < .001 for trend), a BMI increase of 10% or more (RR, 1.13; 95% CI, 1.02-1.26; P = .04 for trend), incident overweight (RR, 1.22; 95% CI,1.06-1.40; P = .03 for trend), and incident obesity (RR, 1.33; 95% CI, 1.13-1.57; P < .001 for trend). Results were supported by sensitivity analyses and additional multivariable analyses including potential mediators such as sleep duration and quality, diet, and physical activity. Conclusions and Relevance: These results suggest that exposure to ALAN while sleeping may be a risk factor for weight gain and development of overweight or obesity. Further prospective and interventional studies could help elucidate this association and clarify whether lowering exposure to ALAN while sleeping can promote obesity prevention.

16.
Occup Environ Med ; 76(8): 511-518, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31167952

RESUMO

OBJECTIVES: Uranium miners in Príbram, Czech Republic were exposed to low and moderate levels of radon gas and other hazards. It is unknown whether these hazards increase the risk of mortality or cancer incidence when compared with the general Czech population. METHODS: A cohort of 16 434 male underground miners employed underground for at least 1 year between 1946 and 1976, and alive and residing in the Czech Republic in 1977, were followed for mortality and cancer incidence through 1992. We compared observed deaths and cancer incidence to expectation based on Czech rates. Standardised mortality ratios (SMRs), standardised incidence ratios (SIRs) and causal mortality ratios were calculated. RESULTS: Underground workers in the Príbram mines had higher rates of death than expected due to all causes (SMR=1.23, 95% CI 1.20 to 1.27), all cancers (SMR=1.52, 95% CI 1.44 to 1.60), lung cancer (SMR=2.12, 95% CI 1.96 to 2.28) and extrathoracic cancer (SMR=1.41, 95% CI 1.15 to 1.77). Similar excess was observed in cancer incidence analyses, with the addition of stomach cancer (SIR=1.37, 95% CI 1.11 to 1.63), liver cancer (SIR=1.70, 95% CI 1.16 to 2.25) and rectal cancer (SIR=1.41, 95% CI 1.16 to 1.66). The SIR was elevated for all leukaemias (SIR=1.51, 95% CI 1.08 to 2.07) and for lymphatic and haematopoietic cancers combined (SIR=1.31, 95% CI 1.05 to 1.61), but results for specific subtypes were imprecise. Deaths due to hazardous mining conditions resulted in 0.33 person-years of life lost per miner. CONCLUSIONS: Occupational exposure to the Príbram mines resulted in excess cancers at several sites, including sites previously linked to radon and uranium exposure. Incidence analyses showed relative excess of several additional cancer subtypes.

17.
J Natl Cancer Inst ; 2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31127946

RESUMO

BACKGROUND: Tobacco and alcohol are well-established risk factors for numerous cancers, yet their relationship to biliary tract cancers remains unclear. METHODS: We pooled data from 26 prospective studies to evaluate associations of cigarette smoking and alcohol consumption with biliary tract cancer risk. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with smoking and alcohol consumption were calculated. Random effects meta-analysis produced summary estimates. All statistical tests were two-sided. RESULTS: Over a period of 38,369,156 person-years of follow-up, 1,391 gallbladder, 758 intrahepatic bile duct, 1,208 extrahepatic bile duct, and 623 ampulla of Vater cancer cases were identified. Ever, former, and current smoking were associated with increased extrahepatic bile duct and ampulla of Vater cancers risk (e.g., current versus never smokers hazard ratio [HR] = 1.69, 95% confidence interval [CI] = 1.34 to 2.13 and 2.22, 95%CI = 1.69 to 2.92, respectively), with dose-response effects for smoking pack-years, duration, and intensity (all P-trend<0.01). Current smoking and smoking intensity were also associated with intrahepatic bile duct cancer (e.g., >40 cigarettes/day versus never smokers HR = 2.15, 95%CI: 1.15 to 4.00; P-trend=0.001). No convincing association was observed between smoking and gallbladder cancer. Alcohol consumption was only associated with intrahepatic bile duct cancer, with increased risk for individuals consuming ≥5 versus 0 drinks/day (HR = 2.35, 95%CI = 1.46 to 3.78; P-trend=0.04). There was evidence of statistical heterogeneity between several cancer sites, particularly between gallbladder cancer and the other biliary tract cancers. CONCLUSIONS: Smoking appears to increase the risk of developing all biliary tract cancers except gallbladder cancer. Alcohol may increase the risk of intrahepatic bile duct cancer. Findings highlight etiologic heterogeneity across the biliary tract.

18.
J Natl Cancer Inst ; 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31143935

RESUMO

BACKGROUND: DNA methylation plays a critical role in breast cancer development. Previous studies have identified DNA methylation marks in white blood cells as promising biomarkers for breast cancer. However, these studies were limited by low statistical power and potential biases. Utilizing a new methodology, we investigated DNA methylation marks for their associations with breast cancer risk. METHODS: Statistical models were built to predict levels of DNA methylation marks using genetic data and DNA methylation data from HumanMethylation450 BeadChip from the Framingham Heart Study (N=1,595). The prediction models were validated using data from the Women's Health Initiative (N=883). We applied these models to genome-wide association study (GWAS) data of 122,977 breast cancer cases and 105,974 controls to evaluate if the genetically predicted DNA methylation levels at CpGs are associated with breast cancer risk. All statistical tests were two-sided. RESULTS: Of the 62,938 CpG sites (CpGs) investigated, statistically significant associations with breast cancer risk were observed for 450 CpGs at a Bonferroni-corrected threshold of P<7.94 × 10-7, including 45 CpGs residing in 18 genomic regions which have not previously been associated with breast cancer risk. Of the remaining 405 CpGs located within 500 kilobase flaking regions of 70 GWAS-identified breast cancer risk variants, the associations for 11 CpGs were independent of GWAS-identified variants. Integrative analyses of genetic, DNA methylation and gene expression data found that 38 CpGs may affect breast cancer risk through regulating expression of 21 genes. CONCLUSION: Our new methodology can identify novel DNA methylation biomarkers for breast cancer risk and can be applied to other diseases.

19.
Environ Res ; 175: 100-107, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31108353

RESUMO

BACKGROUND: The chemicals benzene, toluene, ethylbenzene, and xylenes (BTEX) are neuroactive. Exposures often co-occur because they share common sources. We examined neurologic effects of environmental BTEX exposure among U.S. Gulf coast residents taking into account concomitant exposures. METHODS: We measured blood concentrations of BTEX in 690 Gulf state residents. Neurologic symptoms were ascertained via telephone interview. We used log-binomial regression to estimate associations between blood BTEX levels and self-reported neurologic symptoms independently for the presence of any neurologic, central (CNS), or peripheral nervous system (PNS) symptoms. We estimated associations in single chemical models mutually adjusted for co-occurring BTEX and used weighted quantile sum regression to model associations between the combined BTEX mixture and neurologic symptoms. RESULTS: Half (49%) of participants reported at least one neurologic symptom. Each BTEX chemical was associated with increased CNS and PNS symptoms in single-chemical models comparing the highest to lowest quartile of exposure. After adjusting for coexposures, benzene was associated with CNS symptoms among all participants (PR = 2.13, 95% CI: 1.27, 3.57) and among nonsmokers (PR = 2.30, 95% CI: 1.35, 3.91). After adjusting for coexposures, associations with toluene were apparent only for reporting multiple PNS symptoms (PR = 2.00, 95% CI: 0.96, 4.16). In mixture analyses, a one-quartile increase in BTEX exposure was associated with neurologic symptoms (OR = 1.47, 95% CI: 1.11, 1.98). The weighted quantile sum index weighted benzene most heavily, which was consistent with single chemical analyses. CONCLUSIONS: Increasing blood benzene concentration was associated with increased prevalence of CNS symptoms. In this sample, BTEX-associated neurologic effects are likely driven by exposure to benzene and, to a lesser extent, toluene.

20.
Cancer Res ; 79(15): 3973-3982, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31113819

RESUMO

Biliary tract cancers are rare but highly fatal with poorly understood etiology. Identifying potentially modifiable risk factors for these cancers is essential for prevention. Here we estimated the relationship between adiposity and cancer across the biliary tract, including cancers of the gallbladder (GBC), intrahepatic bile ducts (IHBDC), extrahepatic bile ducts (EHBDC), and the ampulla of Vater (AVC). We pooled data from 27 prospective cohorts with over 2.7 million adults. Adiposity was measured using baseline body mass index (BMI), waist circumference, hip circumference, waist-to-hip, and waist-to-height ratios. HRs and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards models adjusted for sex, education, race, smoking, and alcohol consumption with age as the time metric and the baseline hazard stratified by study. During 37,883,648 person-years of follow-up, 1,343 GBC cases, 1,194 EHBDC cases, 784 IHBDC cases, and 623 AVC cases occurred. For each 5 kg/m2 increase in BMI, there were risk increases for GBC (HR = 1.27; 95% CI, 1.19-1.36), IHBDC (HR = 1.32; 95% CI, 1.21-1.45), and EHBDC (HR = 1.13; 95% CI, 1.03-1.23), but not AVC (HR = 0.99; 95% CI, 0.88-1.11). Increasing waist circumference, hip circumference, waist-to-hip ratio, and waist-to-height ratio were associated with GBC and IHBDC but not EHBDC or AVC. These results indicate that adult adiposity is associated with an increased risk of biliary tract cancer, particularly GBC and IHBDC. Moreover, they provide evidence for recommending weight maintenance programs to reduce the risk of developing these cancers. SIGNIFICANCE: These findings identify a correlation between adiposity and biliary tract cancers, indicating that weight management programs may help minimize the risk of these diseases.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA