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1.
Cancer Res ; 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33853833

RESUMO

While lung cancer is known to be caused by environmental factors, it has also been shown to have genetic components, and the genetic etiology of lung cancer remains understudied. We previously identified a lung cancer risk locus on 6q23-25 using microsatellite data in families with a history of lung cancer. To further elucidate that signal, we performed targeted sequencing on 9 of our most strongly linked families. Two-point linkage analysis of the sequencing data revealed that the signal was heterogeneous and that different families likely had different risk variants. Three specific haplotypes were shared by some of the families: 6q25.3-26 in families 42 and 44, 6q25.2-25.3 in families 47 and 59, and 6q24.2-25.1 in families 30, 33, and 35. Region-based LOD scores and expression data identified the likely candidate genes for each haplotype overlap: ARID1B at 6q25.3, MAP3K4 at 6q26, and UTRN (6q24.1) and PHACTR2 (6q24.2). Further annotation was used to zero in on potential risk variants in those genes. All four genes are good candidate genes for lung cancer risk, having been linked to either lung cancer specifically or other cancers. However, this is the first time any of these genes has been implicated in germline risk. Functional analysis of these four genes is planned for future work.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33672107

RESUMO

Training in environmental health (EH) engages and inspires youth to tackle health promotion and policy change. Yet, there is little guidance on how to successfully nurture and sustain youth engagement. This paper compares four case studies of youth engagement to promote EH in rural and urban communities using the Youth Empowerment Solutions (YES!) framework. Of the case studies in rural (Central Appalachia) and urban (Cincinnati, Ohio) communities, two employ citizen science approaches using PhotoVoice and environmental sampling; one engages youth in a science communication camp; and one focuses on policy advocacy. We compare and contrast these case studies using the YES! Critical Components and Empowerment levels. The case studies were discussed at the 2020 Partnerships in Environmental Public Health Meeting, where participants identified challenges and possible solutions for promoting and maintaining authentic youth engagement in EH research and advocacy. Analysis of the case studies indicated that youth engagement activities focusing on the individual were more common than those targeting the organizational setting or the community. Youth demonstrate agency to impact EH issues in their communities by engaging in hands-on opportunities to practice citizen science and advocacy. Overcoming challenges to authentic young engagement is important to sustain this work.

3.
Respir Med ; 178: 106313, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33550152

RESUMO

BACKGROUND: Ecological evidence suggests that exposure to air pollution affects coronavirus disease 2019 (COVID-19) outcomes. However, no individual-level study has confirmed the association to date. METHODS: We identified COVID-19 patients diagnosed at the University of Cincinnati hospitals and clinics and estimated particulate matter ≤2.5 µm (PM2.5) exposure over a 10-year period (2008-2017) at their residential zip codes. We used logistic regression to evaluate the association between PM2.5 exposure and hospitalizations for COVID-19, adjusting for socioeconomic characteristics and comorbidities. RESULTS: Among the 1128 patients included in our study, the mean (standard deviation) PM2.5 was 11.34 (0.70) µg/m3 for the 10-year average exposure and 13.83 (1.03) µg/m3 for the 10-year maximal exposures. The association between long-term PM2.5 exposure and hospitalization for COVID-19 was contingent upon having pre-existing asthma or chronic obstructive pulmonary (COPD) (Pinteraction = 0.030 for average PM2.5 and Pinteraction = 0.001 for maximal PM2.5). In COVID-19 patients with asthma or COPD, the odds of hospitalization were 62% higher with 1 µg/m3 increment in 10-year average PM2.5 (odds ratio [OR]: 1.62, 95% confidence interval [CI]: 1.00-2.64) and 65% higher with 1 µg/m3 increase in 10-year maximal PM2.5 levels (OR: 1.65, 95% CI: 1.16-2.35). However, among COVID-19 patients without asthma or COPD, PM2.5 exposure was not associated with higher hospitalizations (OR: 0.84, 95% CI: 0.65-1.09 for average PM2.5 and OR: 0.78, 95% CI: 0.65-0.95 for maximal PM2.5). CONCLUSIONS: Long-term exposure to PM2.5 is associated with higher odds of hospitalization in COVID-19 patients with pre-existing asthma or COPD.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Exposição Ambiental/efeitos adversos , Hospitalização/estatística & dados numéricos , Material Particulado/efeitos adversos , Adulto , Asma/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Fatores Socioeconômicos , Fatores de Tempo
4.
J Adolesc Health ; 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33637403

RESUMO

PURPOSE: Earlier timing and faster tempo of puberty have been linked to adolescents' poor mental health. Previous research rarely adjusted for childhood mental health, did not use physical examination to assess puberty, and excluded Latinas and Asian Americans. This study addressed these limitations. METHODS: We followed 822 girls, recruited at ages 6-8, for 8 years. Breast and pubic hair development and anxiety and depressive symptoms were assessed prospectively and repeatedly. Structural equation models tested whether pubertal timing and tempo were associated with adolescent mental health symptoms and whether associations varied by ethnicity. Models were adjusted for childhood mental health symptoms, body mass index, and family income. RESULTS: Earlier breast development was associated with higher depressive symptoms among whites (ß = -.19; p < .01) and higher anxiety symptoms among Latinas (ß = -.26; p < .05), but lower depressive symptoms among Asians (ß = .24, p < .05). Later pubic hair development (b = .24; p < .05) and faster pubic hair tempo (ß = .26; p < .01) were associated with higher anxiety symptoms among Latinas. Faster pubic hair tempo was associated with lower depressive symptoms among Asians (ß = -.34; p < .05). Tempo of breast development showed no associations. CONCLUSIONS: Findings confirmed that earlier breast development was associated with higher mental health symptoms for Latina and white girls but was protective among Asians. Results for pubic hair and pubertal tempo were inconsistent, requiring future examination. While targeted interventions to prevent mental health problems among early-maturing girls are critical, there is variability among who might benefit most.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33302585

RESUMO

Residents in rural Kentucky (KY) and suburban Ohio (OH) expressed concerns about radon exposure and lung cancer. Although 85% of lung cancer cases are caused by tobacco smoke, radon exposure accounts for 10-15% of lung cancer cases. Academic and community members from the University of KY and the University of Cincinnati developed and pilot-tested a family-centered, youth-engaged home radon testing toolkit. The radon toolkit included radon information, and how to test, interpret, and report back findings. We educated youth as citizen scientists and their teachers in human subjects protection and home radon testing using the toolkit in the classroom. Youth citizen scientists explained the study to their parents and obtained informed consent. One hundred students were trained in human subjects protection, 27 had parental permission to be citizen scientists, and 18 homeowners completed surveys. Radon values ranged from < 14.8 Bq/m3 to 277.5 Bq/m3. Youth were interested and engaged in citizen science and this family-centered, school-based project provided a unique opportunity to further the healthy housing and quality education components of the Sustainable Development Goals for 2030. Further research is needed to test the impact of student-led, family-centered citizen science projects in environmental health as part of school curricula.

6.
J Adolesc Health ; 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32888770

RESUMO

PURPOSE: Risk markers for breast cancer include earlier onset of menarche (age at menarche [AAM]) and peak height velocity (PHV). Insulin-like growth factor-1 (IGF-1) is associated with pubertal milestones, as well as cancer risk. This study examined the relationships between pubertal milestones associated with breast cancer risk and hormone changes in puberty. METHODS: This is a longitudinal study of pubertal maturation in 183 girls, recruited at ages 6-7, followed up between 2004 and 2018. Measures included age at onset of puberty, and adult height attained; PHV; AAM; adult height, and serum IGF-1, and estrone-to-androstenedione (E:A) ratio. RESULTS: PHV was greatest in early, and least in late maturing girls; length of the pubertal growth spurt was longest in early, and shortest in late maturing girls. Earlier AAM was related to greater PHV. IGF-1 concentrations tracked significantly during puberty; higher IGF-1 was related to earlier age of PHV, earlier AAM, greater PHV, and taller adult height. Greater E:A ratio was associated with earlier AAM. CONCLUSIONS: Factors driving the association of earlier menarche and pubertal growth with breast cancer risk may be explained through a unifying concept relating higher IGF-1 concentrations, greater lifelong estrogen exposure, and longer pubertal growth period, with an expanded pubertal window of susceptibility.

7.
J Pediatr Adolesc Gynecol ; 33(5): 455-458, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32485297

RESUMO

STUDY OBJECTIVE: Several strategies have been proposed to determine onset of puberty without examination by a trained professional. This study sought to evaluate a novel approach to determine onset of puberty in girls. DESIGN, SETTING, AND PARTICIPANTS: This study used the Cincinnati cohort of the Breast Cancer and the Environment Research Program. Girls were recruited at 6-7 years of age and followed every 6 months in the initial 6 years, and annually thereafter. Breast maturation and foot length were performed at each visit by health professionals certified in those methods. Mothers were asked to provide the age at which they believed that their daughter's shoe size had increased more rapidly. RESULTS: These analyses include 252 participants. Age at increase in shoe size was correlated to age at onset of puberty (r = 0.21) and increase in foot length (r = 0.24). The difference of reported age of increased shoe size was 0.46 years before breast development. CONCLUSION: Reported increase in shoe size occurred somewhat earlier and was significantly correlated to age of breast development. These preliminary results suggest that mother's report of increase in shoe size appear to be as accurate as reports of other indirect methods of determining onset of puberty, such as self- or maternal estimates of breast development.

8.
Cancer Epidemiol Biomarkers Prev ; 29(2): 434-442, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31826912

RESUMO

BACKGROUND: Lung cancer kills more people than any other cancer in the United States. In addition to environmental factors, lung cancer has genetic risk factors as well, though the genetic etiology is still not well understood. We have performed whole exome sequencing on 262 individuals from 28 extended families with a family history of lung cancer. METHODS: Parametric genetic linkage analysis was performed on these samples using two distinct analyses-the lung cancer only (LCO) analysis, where only patients with lung cancer were coded as affected, and the all aggregated cancers (AAC) analysis, where other cancers seen in the pedigree were coded as affected. RESULTS: The AAC analysis yielded a genome-wide significant result at rs61943670 in POLR3B at 12q23.3. POLR3B has been implicated somatically in lung cancer, but this germline finding is novel and is a significant expression quantitative trait locus in lung tissue. Interesting genome-wide suggestive haplotypes were also found within individual families, particularly near SSPO at 7p36.1 in one family and a large linked haplotype spanning 4q21.3-28.3 in a different family. The 4q haplotype contains potential causal rare variants in DSPP at 4q22.1 and PTPN13 at 4q21.3. CONCLUSIONS: Regions on 12q, 7p, and 4q are linked to increased cancer risk in highly aggregated lung cancer families, 12q across families and 7p and 4q within a single family. POLR3B, SSPO, DSPP, and PTPN13 are currently the best candidate genes. IMPACT: Functional work on these genes is planned for future studies and if confirmed would lead to potential biomarkers for risk in cancer.

9.
J Clin Endocrinol Metab ; 104(12): 6079-6089, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31408174

RESUMO

CONTEXT: The age of pubertal onset is influenced by many variables in young girls. Previous studies have not examined sex hormones longitudinally around the time of breast development and their relationship to pubertal onset. OBJECTIVE: We sought to use an unbiased statistical approach to identify phenotypes of sex hormones in young girls and examine their relationship with pubertal milestones. DESIGN AND SETTING: Longitudinal observational study. PARTICIPANTS AND MAIN OUTCOME MEASURES: In 269 girls, serum concentrations of steroid sex hormones [estradiol (E2), estrone, testosterone, and dehydroepiandrosterone sulfate] were measured by HPLC-mass spectrometry at time points before, at, and after thelarche. Girls were classified into four hormone phenotypes using objective principal components and cluster analyses of longitudinal hormone data. The association between the identified phenotypes and age of pubertal milestones was estimated using Cox proportional hazards modeling. RESULTS: Mean ages at thelarche, pubarche, and menarche were 9.02, 9.85, and 12.30 years, respectively. Girls with low levels of all four hormones, phenotype 3b, were youngest at thelarche (8.67 years); those in phenotype 2, with the highest E2 levels and E2 surge 6 months after thelarche, were youngest at menarche (11.87 years) with shortest pubertal tempo. When controlling for race, maternal age of menarche, caregiver education, and body mass, different phenotypes were associated with the age of pubertal events. CONCLUSIONS: Hormone phenotypic clustering can identify clinically relevant subgroups with differing ages of thelarche, pubarche, and menarche. These findings may enhance the understanding of timing of pubertal milestones and risk of adult disease.


Assuntos
Hormônios Esteroides Gonadais/sangue , Puberdade/sangue , Adolescente , Criança , Sulfato de Desidroepiandrosterona/sangue , Estradiol/sangue , Estrona/sangue , Feminino , Humanos , Estudos Longitudinais , Menarca/sangue , Fenótipo , Puberdade/fisiologia , Testosterona/sangue
10.
Environ Res ; 176: 108551, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31376650

RESUMO

BACKGROUND: Age at female puberty is associated with adult morbidities, including breast cancer and diabetes. Hormonally active chemicals are suspected of altering pubertal timing. We examined whether persistent organic pollutants (POPs) are associated with age at menarche in a longitudinal study. METHODS: We analyzed data for females enrolled at age 6-8 years in the Breast Cancer and Environment Research Program from California and Ohio. Participants were followed annually 2004-2013 and provided serum (mean age 7.8 years) for measurement of polychlorinated biphenyl (PCB), organochlorine pesticide (OCP), and polybrominated diphenyl ether (PBDE) concentrations. Age of menarche was assigned based on parental and participant reported dates and ages of menarche. Adjusted hazard ratios (aHRs) for menarchal onset were calculated with Cox proportional regression. Body mass index (BMI), potentially on the causal pathway, was added to parallel analyses. RESULTS: Age of menarche was later with higher summed PCB levels (median 11.9 years in quartile 1 [Q1] versus 12.7 in quartile 4 [Q4]) and OCP levels (12.1 years versus 12.4, respectively). When adjusting for all covariates except BMI, higher POP concentrations were associated with later age at menarche (Q4 versus Q1 aHRs: PBDEs 0.75 [95% CI 0.58, 0.97], PCBs 0.67 [95% CI 0.5, 0.89], and OCPs 0.66 [95% CI 0.50, 0.89]). Additional adjustment for BMI attenuated aHRs; PCB aHR approached the null. CONCLUSION: Findings revealed later onset of menarche with higher concentrations of certain POPs, possibly through an association with BMI. Altered pubertal timing may have long lasting effects on reproductive health and disease risk, so continued attention is important for understanding the biological processes affected by hormonally active chemicals.


Assuntos
Exposição Ambiental/estatística & dados numéricos , Poluentes Ambientais , Hidrocarbonetos Clorados , Menarca , Bifenilos Policlorados , Adulto , California , Criança , Feminino , Humanos , Estudos Longitudinais , Ohio
11.
Environ Res ; 176: 108558, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31271921

RESUMO

BACKGROUND: Perfluorooctanoate (PFOA) has been used extensively in the manufacture of both commercial and household products. PFOA serum concentrations have been associated with adverse health effects, including lower body mass in children and infants. OBJECTIVE: To determine if there is an association between serum PFOA concentration and body mass, serum insulin and lipid profile in exposed young girls. METHODS: We conducted a cross-sectional study of PFAS environmental biomarkers and insulin resistance in 6 to 8 year-old girls from Greater Cincinnati (n=353). In 2004-2006, blood samples were obtained to measure polyfluoroalkyl substances (PFAS), fasting insulin, glucose and lipids. Clinical exams included anthropometric measurements and pubertal maturation staging. Linear regression and mediation analyses, specifically structural equation modeling (SEM), were used to determine the strength and direction of the relationships between PFAS, pubertal maturation status, body mass index (BMI), cholesterol and insulin resistance. RESULTS: The median PFOA (7.7ng/ml) was twice the National Health and Nutrition Examination Survey (2005-2006). Only PFOA, a PFAS sub-species, showed statistically significant relationships with the outcomes. In regression models, PFOA was associated with decreased BMI and waist-to-height ratio (p=0.0008; p=0.0343), HDL-cholesterol (p=0.0046) and had a borderline inverse association with the HOMA Index of insulin resistance (p=0.0864). In SEM, PFOA retained an inverse relationship with BMI (p<0.0001) but the relationships with HOMA and HDL-cholesterol were no longer statistically significant. Pubertal initiation (Tanner breast or pubic stage 2 or greater) and BMI were associated with increased HOMA Index (p<0.0001). CONCLUSIONS: These findings suggest PFOA exposure in young girls affects both BMI and ultimately insulin resistance. In mediation analysis with puberty in the model, the direct effects of PFOA on insulin resistance and were reduced.


Assuntos
Índice de Massa Corporal , Caprilatos , Exposição Ambiental/estatística & dados numéricos , Poluentes Ambientais/análise , Fluorcarbonetos , Resistência à Insulina , Lipídeos/sangue , Criança , Estudos Transversais , Feminino , Humanos , Insulina , Inquéritos Nutricionais , Maturidade Sexual
12.
Ann Epidemiol ; 34: 1-5, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31005553

RESUMO

PURPOSE: Members of the American College of Epidemiology (ACE) Ethics Committee identified current ethics and epidemiology topic areas to consider for further discussion, consultation, teaching opportunities, and conference presentation. This article reflects on the activities of the Committee at the ACE Annual Meeting in New Orleans, Louisiana, September 24-26, 2017. METHODS: The overall aim for the Ethics Committee was to engage members of the College and other audiences and highlight the evolution of ethics and epidemiology since the inception of the original Ethics Guidelines published by the ACE Ethics and Standards of Practice Committee in 2000. The Ethics Committee organized a symposium session at the 2017 Annual Meeting of ACE on the ethics of human subjects research as it relates to specialized areas of epidemiology and the intersecting role of public health. This article presents a summary and further discussion of that symposium session. RESULTS: Three topic areas were presented: an overview of ethics and epidemiology (E.S.P.), very high biomarker levels in environmental epidemiology research (S.M.P.), and the interface of epidemiology, human subjects research, and public health interventions (S.M.). This article begins by reviewing the foundations of epidemiology and public health and the well-known ethical principles of human subjects research. Then, it considers the ethical considerations in the use of population registry data in epidemiological research, environmental epidemiology, and epidemic surveillance and response. This article may form the basis of teaching of ethics principles related to epidemiology and public health and may serve as a companion piece to the original ACE Ethics Guidelines. CONCLUSIONS: Researchers are increasingly faced with ethical considerations in diverse, nontraditional, and specialized areas of epidemiology and public health. This article illustrates these challenges with real-world examples of clinical and population registry data, the study of environmental biomarkers, and Zika virus epidemic; it also reviews relevant ethical principles underpinning these examples and identifies where gaps in knowledge may exist.


Assuntos
Epidemiologia/ética , Comissão de Ética , Saúde Pública/ética , Sujeitos da Pesquisa , Epidemiologia/normas , Ética Médica , Humanos , Zika virus , Infecção por Zika virus
13.
J Clin Endocrinol Metab ; 104(7): 2971-2977, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30882864

RESUMO

CONTEXT: There is a 4- to 5-year variation in age of breast maturation in girls. OBJECTIVE: To examine longitudinal changes in sex hormone values relative to chronologic age and time relative to breast maturation. SETTING AND DESIGN: Longitudinal observational study into which girls were recruited at 6 to 7 years of age and followed up every 6 months. MAIN OUTCOME MEASURES: Maturation status, chronologic age, race, and fasting blood specimen data were obtained. Hormones were analyzed at 6-month intervals between 2 years before and 1 year after breast maturation, using HPLC tandem mass spectroscopy. RESULTS: Estradiol and estrone levels correlated with chronologic age (R = 0.350 and 0.444, respectively); time was correlated relative to breast maturation (R = 0.222 and 0.323, respectively; all correlations, P < 0.0001). In generalized estimating equation (GEE) models, chronologic age and time relative to pubertal onset were significantly associated with serum estradiol, with similar results for estrone. Local estimated scatterplot smoothing for estradiol and estrone, by chronologic age, demonstrated differences between black and white girls, especially between 8.5 and 11 years of age, but not by race in time relative to breast maturation. Testosterone level was correlated to chronologic age (R = 0.362) and time relative to breast maturation (R = 0.259); in the GEE model, only chronologic age was significant. CONCLUSION: Chronologic age as well as time relative to onset of puberty provided unique information regarding estradiol and estrone concentrations in peripubertal girls. Serum estrogen concentrations should be evaluated with reference to chronologic age and race.


Assuntos
Mama/crescimento & desenvolvimento , Estradiol/metabolismo , Estrona/metabolismo , Puberdade/metabolismo , Afro-Americanos , Fatores Etários , Criança , Cromatografia Líquida de Alta Pressão , Sulfato de Desidroepiandrosterona/metabolismo , Grupo com Ancestrais do Continente Europeu , Feminino , Hispano-Americanos , Humanos , Estudos Longitudinais , Puberdade/etnologia , Puberdade/fisiologia , Maturidade Sexual/fisiologia , Espectrometria de Massas em Tandem , Testosterona/metabolismo
14.
Environ Int ; 122: 310-315, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30503317

RESUMO

INTRODUCTION: Cross-sectional studies suggest that postnatal blood lead (PbB) concentrations are negatively associated with child growth. Few studies prospectively examined this association in populations with lower PbB concentrations. We investigated longitudinal associations of childhood PbB concentrations and subsequent anthropometric measurements in a multi-ethnic cohort of girls. METHODS: Data were from The Breast Cancer and the Environment Research Program at three sites in the United States (U.S.): New York City, Cincinnati, and San Francisco Bay Area. Girls were enrolled at ages 6-8 years in 2004-2007. Girls with PbB concentrations collected at ≤10 years old (mean 7.8 years, standard deviation (SD) 0.82) and anthropometry collected at ≥3 follow-up visits were included (n = 683). The median PbB concentration was 0.99 µg/d (10th percentile = 0.59 µg/dL and 90th percentile = 2.00 µg/dL) and the geometric mean was 1.03 µg/dL (95% Confidence Interval (CI): 0.99, 1.06). For analyses, PbB concentrations were dichotomized as <1 µg/dL (n = 342) and ≥1 µg/dL (n = 341). Anthropometric measurements of height, body mass index (BMI), waist circumference (WC), and percent body fat (%BF) were collected at enrollment and follow-up visits through 2015. Linear mixed effects regression estimated how PbB concentrations related to changes in girls' measurements from ages 7-14 years. RESULTS: At 7 years, mean difference in height was -2.0 cm (95% CI: -3.0, -1.0) for girls with ≥1 µg/dL versus <1 µg/dL PbB concentrations; differences persisted, but were attenuated, with age to -1.5 cm (95% CI: -2.5, -0.4) at 14 years. Mean differences for BMI, WC, and BF% at 7 years between girls with ≥1 µg/dL versus <1 µg/dL PbB concentrations were -0.7 kg/m2 (95% CI: -1.2, -0.2), -2.2 cm (95% CI: -3.8, -0.6), and -1.8% (95% CI: -3.2, -0.4), respectively. Overall, these differences generally persisted with advancing age and at 14 years, differences were -0.8 kg/m2 (95% CI: -1.5, -0.02), -2.9 cm (95% CI: -4.8, -0.9), and -1.7% (95% CI: -3.1, -0.4) for BMI, WC, and BF%, respectively. CONCLUSIONS: These findings suggest that higher concentrations of PbB during childhood, even though relatively low by screening standards, may be inversely associated with anthropometric measurements in girls.


Assuntos
Índice de Massa Corporal , Exposição Ambiental , Chumbo/sangue , Circunferência da Cintura , Adolescente , Criança , Estudos Transversais , Exposição Ambiental/análise , Exposição Ambiental/estatística & dados numéricos , Feminino , Humanos , Cidade de Nova Iorque/epidemiologia
15.
Reprod Toxicol ; 84: 26-31, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30579999

RESUMO

Endometriosis is a complex disease impacted by the hormonal and immune systems. Cytokines and chemokines are serum biomarkers that maybe useful to develop a noninvasive disease diagnosis. Individuals in the Fernald Community Cohort were exposed to uranium, a heavy metal with radioactive properties and estrogenic potential; therefore, serum samples from women in this cohort with or without uranium and with or without endometriosis were compared for alterations in chemokine, cytokine, and matrix metalloproteinase (MMP) levels. Control women were matched to endometriosis cases by uranium exposure, age, and body mass index. MMP levels were not altered. Five chemokines and one cytokine significantly increased in endometriosis cases versus controls irrespective of uranium exposure. Uranium exposure alone was associated with an increase in inflammatory chemokines. The majority of the elevated chemokines in endometriosis cases play important roles in attracting T helper-2 cells, which may be vital to understanding the immune response in endometriosis.


Assuntos
Quimiocinas/sangue , Endometriose/sangue , Exposição à Radiação/efeitos adversos , Poluentes Radioativos/toxicidade , Urânio/toxicidade , Adulto , Estudos de Casos e Controles , Endometriose/epidemiologia , Feminino , Humanos , Metaloproteinases da Matriz/sangue , Ohio/epidemiologia
16.
Am J Surg ; 216(4): 809-812, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30270029

RESUMO

BACKGROUND: Pregnancy-associated breast cancer (PABC) is the most common malignancy in pregnancy. However due to its infrequent occurrence, PABC continues to be poorly understood. METHODS: We performed a retrospective study using self-reported data from 1079 eligible women in a regional breast cancer registry. RESULTS: The PABC cases were more likely than non-PABCs to be younger than age 35 and have nodal involvement at diagnosis. Despite diagnosis at a young age, there was not an association between PABC and family history. For method of diagnosis, PABC was found on self-exam, while non-PABCs were found on mammography. CONCLUSION: In conclusion, PABC is rarely detected by mammography and diagnosis is highly dependent on detection during self-breast exam. Women who are or recently were pregnant should be encouraged to perform regular self-breast exams to report any changes for further evaluation. Patient and clinician education regarding risk and realities of PABC is essential.


Assuntos
Neoplasias da Mama/etiologia , Lactação , Complicações Neoplásicas na Gravidez/etiologia , Transtornos Puerperais/etiologia , Adulto , Neoplasias da Mama/diagnóstico , Autoexame de Mama , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Gravidez , Complicações Neoplásicas na Gravidez/diagnóstico , Transtornos Puerperais/diagnóstico , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Autorrelato
17.
Environ Pollut ; 242(Pt A): 894-904, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30373035

RESUMO

Perfluoroalkyl substances (PFAS) are a diverse class of manufactured compounds used in a wide range of industrial processes and consumer products and have been detected in human serum worldwide. Previous cross-sectional and cohort studies in humans have suggested exposure to PFAS is associated with a wide array of chronic diseases, including endocrine disruption, developmental health effects, cancer and metabolic changes. We examined the associations between a panel of eight PFAS and indicators of thyroid disruption, kidney function, and body mass index (BMI), all of which were measured at repeated time points (1990-2008) over the course of the study. Participants (N = 210) were selected from the Fernald Community Cohort based on household water supply from a PFAS-contaminated aquifer. In adjusted repeated measures models, we observed several notable associations between serum PFAS and thyroid hormones as well as kidney function as measured by estimated glomerular filtration rate (eGFR). An interquartile (IQR) increase in serum PFOS was associated with a 9.75% (95% CI = 1.72, 18.4) increase in thyroid stimulating hormone. An IQR increase in serum PFNA, PFHxS, and PFDeA was associated with a -1.61% (95% CI = -3.53, -0.59), -2.06% (95% CI = -3.53, -0.59), and -2.20% (95% CI = -4.25, -0.14) change in eGFR, respectively. On the other hand, an IQR increase in serum Me-PFOSA was associated with a 1.53% (95% CI = 0.34, 2.73) increase in eGFR. No significant associations with BMI and serum PFAS were noted. Our findings are in agreement with previous reports that serum PFAS are associated with altered kidney and thyroid function.


Assuntos
Exposição Ambiental/análise , Fluorcarbonetos/sangue , Hormônios Tireóideos/sangue , Ácidos Alcanossulfônicos/sangue , Índice de Massa Corporal , Caprilatos/sangue , Estudos de Coortes , Estudos Transversais , Disruptores Endócrinos/sangue , Poluentes Ambientais/sangue , Humanos , Tireotropina
18.
Int J Hyg Environ Health ; 221(7): 1040-1046, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30025914

RESUMO

BACKGROUND: Measurement of environmental biomarkers in biomedia is increasingly used as a method of exposure characterization in human population studies. Reporting the results of biomarker measurements back to study participants has been controversial, including questions of ethics and whether the study participants would want to receive and would understand the results. METHODS: Recently we mailed individual measurements of two serum biomarkers, perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) to participants in three exposure studies of persons living in the Ohio River Valley, of whom 60 were parents of children who had been sampled. Many had serum concentrations of PFOA above the US population 95th percentile value. Reporting forms used in the three studies were somewhat different (either tables or charts for comparison to US population values) and varied in complexity. With all reports, we included information about concentrations of PFOA and PFOS in the general population, and a survey designed to ascertain the opinions of the study participants about the information they received. RESULTS: Approximately 33% (273/821) returned the survey, and of those, 96% reported that they were pleased that we had sent them the report. Most (86%) responded that the results were easy to understand and the enclosed fact sheet was helpful in answering questions (87%). Regarding the amount of information, most felt that we provided the "right amount" (78%) but some "too much" (7%) and some "too little" (15%). The majority (53%) were surprised at their serum concentrations. Of those with serum values > 13.0 ng/mL, 74% responded that they thought their serum concentration was "high", but only 22% of those with serum concentrations ≤5.6 responded that their concentration was "low". Surprisingly, many talked to no one about their levels; those who did were most likely to discuss the report with family members. CONCLUSIONS: Reporting back individual environmental biomarker results is generally well received by study participants, and those with high concentrations perceived them to be high. Questions remain as to why study participants did not discuss their results with others.


Assuntos
Ácidos Alcanossulfônicos/sangue , Caprilatos/sangue , Poluentes Ambientais/sangue , Fluorcarbonetos/sangue , Conhecimentos, Atitudes e Prática em Saúde , Adolescente , Adulto , Biomarcadores/sangue , Criança , Comunicação , Compreensão , Água Potável , Exposição Ambiental/análise , Feminino , Humanos , Kentucky , Masculino , Pessoa de Meia-Idade , Ohio , Percepção , Inquéritos e Questionários , West Virginia , Adulto Jovem
19.
J Thorac Oncol ; 13(10): 1483-1495, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29981437

RESUMO

BACKGROUND: Genome-wide association studies are widely used to map genomic regions contributing to lung cancer (LC) susceptibility, but they typically do not identify the precise disease-causing genes/variants. To unveil the inherited genetic variants that cause LC, we performed focused exome-sequencing analyses on genes located in 121 genome-wide association study-identified loci previously implicated in the risk of LC, chronic obstructive pulmonary disease, pulmonary function level, and smoking behavior. METHODS: Germline DNA from 260 case patients with LC and 318 controls were sequenced by utilizing VCRome 2.1 exome capture. Filtering was based on enrichment of rare and potential deleterious variants in cases (risk alleles) or controls (protective alleles). Allelic association analyses of single-variant and gene-based burden tests of multiple variants were performed. Promising candidates were tested in two independent validation studies with a total of 1773 case patients and 1123 controls. RESULTS: We identified 48 rare variants with deleterious effects in the discovery analysis and validated 12 of the 43 candidates that were covered in the validation platforms. The top validated candidates included one well-established truncating variant, namely, BRCA2, DNA repair associated gene (BRCA2) K3326X (OR = 2.36, 95% confidence interval [CI]: 1.38-3.99), and three newly identified variations, namely, lymphotoxin beta gene (LTB) p.Leu87Phe (OR = 7.52, 95% CI: 1.01-16.56), prolyl 3-hydroxylase 2 gene (P3H2) p.Gln185His (OR = 5.39, 95% CI: 0.75-15.43), and dishevelled associated activator of morphogenesis 2 gene (DAAM2) p.Asp762Gly (OR = 0.25, 95% CI: 0.10-0.79). Burden tests revealed strong associations between zinc finger protein 93 gene (ZNF93), DAAM2, bromodomain containing 9 gene (BRD9), and the gene LTB and LC susceptibility. CONCLUSION: Our results extend the catalogue of regions associated with LC and highlight the importance of germline rare coding variants in LC susceptibility.


Assuntos
Variação Genética/genética , Estudo de Associação Genômica Ampla/métodos , Neoplasias Pulmonares/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco
20.
Carcinogenesis ; 39(9): 1135-1140, 2018 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-29924316

RESUMO

To identify genetic variation associated with lung cancer risk, we performed a genome-wide association analysis of 685 lung cancer cases that had a family history of two or more first or second degree relatives compared with 744 controls without lung cancer that were genotyped on an Illumina Human OmniExpressExome-8v1 array. To ensure robust results, we further evaluated these findings using data from six additional studies that were assembled through the Transdisciplinary Research on Cancer of the Lung Consortium comprising 1993 familial cases and 33 690 controls. We performed a meta-analysis after imputation of all variants using the 1000 Genomes Project Phase 1 (version 3 release date September 2013). Analyses were conducted for 9 327 222 SNPs integrating data from the two sources. A novel variant on chromosome 4p15.31 near the LCORL gene and an imputed rare variant intergenic between CDKN2A and IFNA8 on chromosome 9p21.3 were identified at a genome-wide level of significance for squamous cell carcinomas. Additionally, associations of CHRNA3 and CHRNA5 on chromosome 15q25.1 in sporadic lung cancer were confirmed at a genome-wide level of significance in familial lung cancer. Previously identified variants in or near CHRNA2, BRCA2, CYP2A6 for overall lung cancer, TERT, SECISPB2L and RTEL1 for adenocarcinoma and RAD52 and MHC for squamous carcinoma were significantly associated with lung cancer.


Assuntos
Adenocarcinoma/genética , Carcinoma de Células Escamosas/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Estudos de Casos e Controles , Cromossomos Humanos Par 15/genética , Cromossomos Humanos Par 4 , Cromossomos Humanos Par 9/genética , Humanos , Pulmão/patologia , Anamnese , Polimorfismo de Nucleotídeo Único/genética
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