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Importance: Few studies have investigated whether the associations between pregnancy-related factors and breast cancer (BC) risk differ by underlying BC susceptibility. Evidence regarding variation in BC risk is critical to understanding BC causes and for developing effective risk-based screening guidelines. Objective: To examine the association between pregnancy-related factors and BC risk, including modification by a of BC where scores are based on age and BC family history. Design, Setting, and Participants: This cohort study included participants from the prospective Family Study Cohort (ProF-SC), which includes the 6 sites of the Breast Cancer Family Registry (US, Canada, and Australia) and the Kathleen Cuningham Foundation Consortium (Australia). Analyses were performed in a cohort of women enrolled from 1992 to 2011 without any personal history of BC who were followed up through 2017 with a median (range) follow-up of 10 (1-23) years. Data were analyzed from March 1992 to March 2017. Exposures: Parity, number of full-term pregnancies (FTP), age at first FTP, years since last FTP, and breastfeeding. Main Outcomes and Measures: BC diagnoses were obtained through self-report or report by a first-degree relative and confirmed through pathology and data linkages. Cox proportional hazards regression models estimated hazard ratios (HR) and 95% CIs for each exposure, examining modification by PARS of BC. Differences were assessed by estrogen receptor (ER) subtype. Results: The study included 17â¯274 women (mean [SD] age, 46.7 [15.1] years; 791 African American or Black participants [4.6%], 1399 Hispanic or Latinx participants [8.2%], and 13â¯790 White participants [80.7%]) with 943 prospectively ascertained BC cases. Compared with nulliparous women, BC risk was higher after a recent pregnancy for those women with higher PARS (last FTP 0-5 years HR for interaction, 1.53; 95% CI, 1.13-2.07; P for interaction < .001). Associations between other exposures were limited to ER-negative disease. ER-negative BC was positively associated with increasing PARS and increasing years since last FTP (P for interaction < .001) with higher risk for recent pregnancy vs nulliparous women (last FTP 0-5 years HR for interaction, 1.54; 95% CI, 1.03-2.31). ER-negative BC was positively associated with increasing PARS and being aged 20 years or older vs less than 20 years at first FTP (P for interaction = .002) and inversely associated with multiparity vs nulliparity (P for interaction = .01). Conclusions and Relevance: In this cohort study of women with no prior BC diagnoses, associations between pregnancy-related factors and BC risk were modified by PARS, with greater associations observed for ER-negative BC.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/epidemiologia , Gravidez , Adulto , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Austrália/epidemiologia , Canadá/epidemiologia , Paridade , Estados Unidos/epidemiologia , Sistema de Registros , Predisposição Genética para Doença , Estudos de Coortes , Aleitamento Materno/estatística & dados numéricosRESUMO
Even though many environmental carcinogens have been identified, studying their effects on specific cancers has been challenging in non-occupational settings where exposures may be chronic but at lower levels. Although exposure measurement methods have improved considerably, along with key opportunities to integrate multi-omic platforms, there remain challenges that need to be considered particularly around the design of studies. Cancer studies typically exclude individuals with prior cancers and start recruitment in midlife. This translates into a failure to capture individuals who may have been most susceptible because of both germline susceptibility and higher early life exposures that lead to premature mortality from cancer and/or other environmentally caused diseases like lung diseases. Using the example of breast cancer, we demonstrate how integration of susceptibility, both for cancer risk and exposure windows, may provide a more complete picture regarding the harm of many different environmental exposures. Choice of study design is critical to examine the effects of environmental exposures, and it will not be enough to just rely on the availability of existing cohorts and samples within these cohorts. In contrast, new, diverse, early onset case-control studies may provide many benefits to understanding the impact of environmental exposures on cancer risk and mortality.
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Employment and working conditions are strong social determinants of health, yet many epidemiological studies fail to account for their impact on life expectancy calculations. Integration of working conditions into health estimates requires both valid methodology and data sources. Using the French National Health and Career Path survey and French life tables, we quantified the impact of four major work-related factors (lack of job control, job insecurity, unemployment, and occupational physical activity) in explaining socio-occupational inequalities in life expectancy. Using a formula-based approach, we computed work-related loss in life expectancy by socio-occupational group separately by sex. Based on life expectancy at age 35, we estimated a range from 1.3 to 3.3 years of life lost for men, and from 0.5 to 1.8 years for women are attributed to a combination of these four key factors. Although subject to sources of under- and over-estimation, the differential life expectancy at age 35 between senior executives and manual workers would substantially decrease, had these exposures been set at the theoretical minimum level. This proof-of-concept analysis demonstrates the utility of accounting for occupational factors and the potential to quantify the improvements in life expectancy by modifying working and employment conditions.
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Despite widespread use of hair products globally, little is known about the prevalence and patterns of use in populations outside the United States. As some hair products contain endocrine-disrupting chemicals (EDCs) and EDCs have been linked to breast cancer, which is increasing globally, in this study, we addressed key knowledge gaps about hair product use and practices, and perceptions of use among women in two counties in Kenya. Using community-engaged approaches in Embu and Nakuru, Kenya, we recruited women aged 15-50 years to complete a questionnaire that ascertained hair product use in the last 7-14 days, ever using hair dyes and chemical relaxers, and participants' perceptions or harm around hair product use. In multivariable-adjusted regression models, we evaluated associations between participants' sociodemographic characteristics and perceptions of hair product use in relation to if they have ever used hair dyes and relaxers. In our sample of 746 women (mean age, 30.4 ± 8.1 years), approximately one-third of participants reported ever using permanent and/or semi-permanent hair dyes, with approximately one-fifth reporting current use. Almost 60% reported ever using chemical relaxers, with a little over one-third reporting current use. Increasing age and having an occupation in the sales and service industry were statistically significant predictors of hair dye use (OR 1.04, 95% CI: 1.02-1.06 and OR 2.05, 95% CI: 1.38-3.03, respectively) and relaxer use (OR 1.03, 95% CI: 1.01-1.06 and OR 1.93, 95% CI: 1.30-2.87). On average, participants reported moderate-to-high levels of concern about exposures and general health effects from using hair products, and relatively high levels of perceived risk of breast cancer related to hair product use. However, in contrast to our hypotheses, we observed mixed evidence regarding whether higher levels of perceived risk were associated with lower odds of ever using hair dyes and relaxers. These findings add new knowledge to the extant literature on hair product use among women in Kenya, where breast cancer incidence rates are increasing. Improving the understanding of patterns of use of specific products and their chemical ingredients-which may be hormone disruptors or carcinogens-and exploring the role of environmental health literacy are critical for developing interventions to reduce potentially harmful exposures found in these products.
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Neoplasias da Mama , Tinturas para Cabelo , Humanos , Quênia/epidemiologia , Feminino , Adulto , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/induzido quimicamente , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Conhecimentos, Atitudes e Prática em Saúde , Inquéritos e QuestionáriosRESUMO
Purpose: This study aimed to determine the prevalence of endocrine resistance in a cohort of Hispanic Mexican breast cancer (BC) patients receiving care at Instituto Nacional de Cancerología (INCan). Additionally, the clinical-pathological factors associated with endocrine resistance were identified, and their impact on patient survival was explored. Methods: A retrospective analysis of 200 BC patients who attended INCan between 2012 and 2016 with estrogen receptor (ER) and progesterone receptor (PR) positive tumors was made. Endocrine resistance was defined according to the International Consensus Guidelines for Advance Breast Cancer 2 definition. Their clinicopathological characteristics were analyzed to determine the association with endocrine resistance presence. We used sensitivity analyses and multivariate-adjusted logistic regressions, Kaplan-Meier curves, and multivariate-adjusted Cox regressions. P-value < 0.05 was considered as statistically significant. Results: Endocrine resistance was observed in 32.5% of patients included in this study. The distinction between hormone resistance and sensitivity was influenced by tumor size and node status. It had a mean diameter of 7.15 cm in endocrine resistance cases compared to 5.71 cm in non-endocrine, with N3 status present in 20% of endocrine resistance cases versus only 2.2% in non-endocrine (p-value < 0.001). The clinical stage exhibited a strong association with endocrine resistance (Risk Ratio [RR] 4.39, 95% confidence interval [95%CI] 1.50, 11.43). Furthermore, endocrine resistance significantly impacted mortality during the follow-up, with a Hazard Ratio [HR] of 23.7 (95%CI 5.20, 108.42) in multivariable-adjusted models. However, a complete pathological response reduced the endocrine resistance risk, as demonstrated by a Risk Ratio (RR) of 0.15 (95% CI 0.03, 0.75). Conclusions: Advanced clinical stage at diagnosis predicted endocrine resistance in Hispanic Mexican BC patients. Complete pathologic response in locally advanced disease patients was also a key predictor of endocrine resistance. These results indicated that endocrine resistance was a critical factor in BC during follow-up.
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Deep learning-based mammographic evaluations could noninvasively assess response to breast cancer chemoprevention. We evaluated change in a convolutional neural network-based breast cancer risk model applied to mammograms among women enrolled in SWOG S0812, which randomly assigned 208 premenopausal high-risk women to receive oral vitamin D3 20â000 IU weekly or placebo for 12 months. We applied the convolutional neural network model to mammograms collected at baseline (n = 109), 12 months (n = 97), and 24 months (n = 67) and compared changes in convolutional neural network-based risk score between treatment groups. Change in convolutional neural network-based risk score was not statistically significantly different between vitamin D and placebo groups at 12 months (0.005 vs 0.002, P = .875) or at 24 months (0.020 vs 0.001, P = .563). The findings are consistent with the primary analysis of S0812, which did not demonstrate statistically significant changes in mammographic density with vitamin D supplementation compared with placebo. There is an ongoing need to evaluate biomarkers of response to novel breast cancer chemopreventive agents.
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Densidade da Mama , Neoplasias da Mama , Colecalciferol , Aprendizado Profundo , Suplementos Nutricionais , Mamografia , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/prevenção & controle , Densidade da Mama/efeitos dos fármacos , Pessoa de Meia-Idade , Colecalciferol/administração & dosagem , Adulto , Vitamina D/administração & dosagem , Pré-Menopausa , Redes Neurais de Computação , Medição de RiscoRESUMO
Genome-wide association studies (GWAS) have been helpful in identifying genetic variants predicting cancer risk and providing new insights into cancer biology. Increasing use of genetically informed care, as well as genetically informed prevention and treatment strategies, have also drawn attention to some of the inherent limitations of cancer genetic data. Specifically, genetic endowment is lifelong. However, those recruited into cancer studies tend to be middle-aged or older people, meaning the exposure most likely starts before recruitment, as opposed to exposure and recruitment aligning, as in a trial or a target trial. Studies in survivors can be biased as a result of depletion of the susceptibles, here specifically due to genetic vulnerability and the cancer of interest or a competing risk. In addition, including prevalent cases in a case-control study will make the genetics of survival with cancer look harmful (Neyman bias). Here, we describe ways of designing GWAS to maximize explanatory power and predictive utility, by reducing selection bias due to only recruiting survivors and reducing Neyman bias due to including prevalent cases alongside using other techniques, such as selection diagrams, age-stratification, and Mendelian randomization, to facilitate GWAS interpretability and utility.
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PURPOSE: Nationally legislated dense breast notification (DBN) informs women of their breast density (BD) and the impact of BD on breast cancer risk and detection, but consequences for screening participation are unclear. We evaluated the association of DBN in New York State (NYS) with subsequent screening mammography in a largely Hispanic/Latina cohort. METHODS: Women aged 40-60 were surveyed in their preferred language (33% English, 67% Spanish) during screening mammography from 2016 to 2018. We used clinical BD classification from mammography records from 2013 (NYS DBN enactment) through enrollment (baseline) to create a 6-category variable capturing prior and new DBN receipt (sent only after clinically dense mammograms). We used this variable to compare the number of subsequent mammograms (0, 1, ≥ 2) from 10 to 30 months after baseline using ordinal logistic regression. RESULTS: In a sample of 728 women (78% foreign-born, 72% Hispanic, 46% high school education or less), first-time screeners and women who received DBN for the first time after prior non-dense mammograms had significantly fewer screening mammograms within 30 months of baseline (Odds Ratios range: 0.33 (95% Confidence Interval (CI) 0.12-0.85) to 0.38 (95% CI 0.17-0.82)) compared to women with prior mammography but no DBN. There were no differences in subsequent mammogram frequency between women with multiple DBN and those who never received DBN. Findings were consistent across age, language, health literacy, and education groups. CONCLUSION: Women receiving their first DBN after previous non-dense mammograms have lower mammography participation within 2.5 years. DBN has limited influence on screening participation of first-time screeners and those with persistent dense mammograms.
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Densidade da Mama , Neoplasias da Mama , Detecção Precoce de Câncer , Hispânico ou Latino , Mamografia , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/etnologia , Estudos de Coortes , Programas de Rastreamento , New York/epidemiologiaRESUMO
Introduction: Exposure to endocrine disrupting chemicals (EDCs), such as phthalates, can negatively impact maternal and child health, contributing to impaired fetal growth, preterm birth, and pregnancy complications, as well as increased downstream risks of cardiometabolic disease and breast cancer. Notably, women of color (WOC) are the largest consumers of personal care products, which are a common source of EDC exposure. Methods: The Let's Reclaim Our Ancestral Roots (Let's R.O.A.R) Pilot Study developed an educational intervention delivered during pregnancy to promote reduced use of phthalate-containing hair care products (HCPs). This mixed-methods study included: (1) a quantitative analysis and (2) a qualitative analysis of the educational sessions and the semi-structured focus groups to evaluate the factors that influenced the hair care practices and product choices of WOC at various stages of life, including their current pregnancy (hereafter referred to as the hair journey). During the sessions, participants learned about EDCs (with a focus on phthalates), the unequal burden of exposure for WOC, adverse implications of exposure, and exposure reduction strategies. Focus group sessions provided insight into participants' hair journeys from childhood to the current pregnancy and explored factors during their hair product selection process. All sessions were transcribed and imported into NVivo Version 12 for coding and thematic analysis. Results: A total of 46 individuals were enrolled in the study, and 31 participated in an educational session. This current work synthesizes the qualitative analysis of this study. We identified two important life stages (before and after gaining agency over hair care practices and product choices) and three dominant themes related to HCP use: (1) products that impacted the hair journey, which involved all mentions of hair products, (2) factors that influenced the hair journey, which included individuals or entities that shaped participants' hair experiences, and (3) the relationship between hair and sense of self, where sense of self was defined as the alignment of one's inner and outer beauty. Conclusion: The themes intersected and impacted the participants' hair journey. Cultural integration was a sub-theme that overlapped within the dominant themes and participants discussed the effect of traditions on their hair experiences.
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The impact of common environmental exposures in combinations with socioeconomic and lifestyle factors on cancer development, particularly for young adults, remains understudied. Here, we leveraged environmental and cancer incidence data collected in New York State at the county level to examine the association between 31 exposures and 10 common cancers (i.e., lung and bronchus, thyroid, colorectal, kidney and renal pelvis, melanoma, non-Hodgkin lymphoma, and leukemia for both sexes; corpus uteri and female breast cancer; prostate cancer), for three age groups (25-49, 50-69, and 70-84 year-olds). For each cancer, we stratified by age group and sex, and applied regression models to examine the associations with multiple exposures simultaneously. The models included 642,013 incident cancer cases during 2010-2018 and found risk factors consistent with previous reports (e.g., smoking and physical inactivity). Models also found positive associations between ambient air pollutants (ozone and PM2.5) and prostate cancer, female breast cancer, and melanoma of the skin across multiple population strata. Additionally, the models were able to better explain the variation in cancer incidence data among 25-49 year-olds than the two older age groups. These findings support the impact of common environmental exposures on cancer development, particularly for younger age groups.
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Poluentes Atmosféricos , Poluição do Ar , Neoplasias da Mama , Melanoma , Neoplasias da Próstata , Masculino , Adulto Jovem , Humanos , Idoso , Incidência , New York , Poluentes Atmosféricos/análise , Neoplasias da Mama/epidemiologia , Exposição Ambiental , Neoplasias da Próstata/induzido quimicamente , Material Particulado/efeitos adversos , Poluição do Ar/análiseRESUMO
Importance: Racially minoritized and socioeconomically disadvantaged populations are currently underrepresented in clinical trials. Data-driven, quantitative analyses and strategies are required to help address this inequity. Objective: To systematically analyze the geographical distribution of self-identified racial and socioeconomic demographics within commuting distance to cancer clinical trial centers and other hospitals in the US. Design, Setting, and Participants: This longitudinal quantitative study used data from the US Census 2020 Decennial and American community survey (which collects data from all US residents), OpenStreetMap, National Cancer Institute-designated Cancer Centers list, Nature Index of Cancer Research Health Institutions, National Trial registry, and National Homeland Infrastructure Foundation-Level Data. Statistical analyses were performed on data collected between 2006 and 2020. Main Outcomes and Measures: Population distributions of socioeconomic deprivation indices and self-identified race within 30-, 60-, and 120-minute 1-way driving commute times from US cancer trial sites. Map overlay of high deprivation index and high diversity areas with existing hospitals, existing major cancer trial centers, and commuting distance to the closest cancer trial center. Results: The 78 major US cancer trial centers that are involved in 94% of all US cancer trials and included in this study were found to be located in areas with socioeconomically more affluent populations with higher proportions of self-identified White individuals (+10.1% unpaired mean difference; 95% CI, +6.8% to +13.7%) compared with the national average. The top 10th percentile of all US hospitals has catchment populations with a range of absolute sum difference from 2.4% to 35% from one-third each of Asian/multiracial/other (Asian alone, American Indian or Alaska Native alone, Native Hawaiian or Other Pacific Islander alone, some other race alone, population of 2 or more races), Black or African American, and White populations. Currently available data are sufficient to identify diverse census tracks within preset commuting times (30, 60, or 120 minutes) from all hospitals in the US (N = 7623). Maps are presented for each US city above 500â¯000 inhabitants, which display all prospective hospitals and major cancer trial sites within commutable distance to racially diverse and socioeconomically disadvantaged populations. Conclusion and Relevance: This study identified biases in the sociodemographics of populations living within commuting distance to US-based cancer trial sites and enables the determination of more equitably commutable prospective satellite hospital sites that could be mobilized for enhanced racial and socioeconomic representation in clinical trials. The maps generated in this work may inform the design of future clinical trials or investigations in enrollment and retention strategies for clinical trials; however, other recruitment barriers still need to be addressed to ensure racial and socioeconomic demographics within the geographical vicinity of a clinical site can translate to equitable trial participant representation.
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Ensaios Clínicos como Assunto , Acessibilidade aos Serviços de Saúde , Neoplasias , Viagem , Humanos , Estados Unidos , Viagem/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Ensaios Clínicos como Assunto/estatística & dados numéricos , Neoplasias/terapia , Neoplasias/etnologia , Fatores Socioeconômicos , Fatores de Tempo , Institutos de Câncer/estatística & dados numéricos , Estudos LongitudinaisRESUMO
Young breast and bowel cancers (e.g., those diagnosed before age 40 or 50 years) have far greater morbidity and mortality in terms of years of life lost, and are increasing in incidence, but have been less studied. For breast and bowel cancers, the familial relative risks, and therefore the familial variances in age-specific log(incidence), are much greater at younger ages, but little of these familial variances has been explained. Studies of families and twins can address questions not easily answered by studies of unrelated individuals alone. We describe existing and emerging family and twin data that can provide special opportunities for discovery. We present designs and statistical analyses, including novel ideas such as the VALID (Variance in Age-specific Log Incidence Decomposition) model for causes of variation in risk, the DEPTH (DEPendency of association on the number of Top Hits) and other approaches to analyse genome-wide association study data, and the within-pair, ICE FALCON (Inference about Causation from Examining FAmiliaL CONfounding) and ICE CRISTAL (Inference about Causation from Examining Changes in Regression coefficients and Innovative STatistical AnaLysis) approaches to causation and familial confounding. Example applications to breast and colorectal cancer are presented. Motivated by the availability of the resources of the Breast and Colon Cancer Family Registries, we also present some ideas for future studies that could be applied to, and compared with, cancers diagnosed at older ages and address the challenges posed by young breast and bowel cancers.
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Incidence of early-onset (diagnosed before age 50) colorectal cancer (EOCRC) has increased alarmingly since the 1990s in the United States. This study investigated what environmental exposures may have driven this increase. We obtained EOCRC incidence data from the Surveillance, Epidemiology, and End Results Program, and data for 11 exposures, for example, body mass index (BMI), from long-term national surveys. We aggregated these data for 30 to 49-year-olds during 1992 to 2016 by population subgroups defined by calendar period, age, race and sex, and used negative binomial regression models to identify and estimate associations of EOCRC with multiple exposures. Furthermore, we used counterfactual modeling to quantify contributions of identified risk factors to EOCRC incidence. The top models (with lowest Bayesian Information Criteria) consistently identified excess body weight, represented by overweight and obesity (BMI ≥25) or obesity alone (BMI ≥30), as the strongest risk factor. The best-performing model estimated increased EOCRC incidence due to overweight and obesity, with an incidence rate ratio (95% confidence interval) of 1.20 (1.17-1.22) for white men, 1.04 (1.00-1.08) for black men, 1.17 (1.15-1.21) for white women and 1.03 (0.97-1.08) for black women. Increases in overweight and obesity prevalence contributed to an estimated 30% (standard error: 1%) for men and 28% (standard error: 2%) for women of ECORC incidence during 1992 to 2016. These findings suggest excess body weight substantially contributed to and is likely a primary driver of the rising incidence of EOCRC in the United States. Prevention of excess weight gain may help lower colorectal cancer risk early in life.
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Neoplasias Colorretais , Sobrepeso , Masculino , Humanos , Feminino , Estados Unidos/epidemiologia , Pessoa de Meia-Idade , Sobrepeso/epidemiologia , Incidência , Teorema de Bayes , Obesidade/complicações , Obesidade/epidemiologia , Fatores de Risco , Aumento de Peso , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologiaRESUMO
BACKGROUND: There is limited research on whether physical activity (PA) in early childhood is associated with the timing of pubertal events in girls. METHODS: We used data collected over 2011-16 from the LEGACY Girls Study (n = 984; primarily aged 6-13 years at study enrolment), a multicentre North American cohort enriched for girls with a breast cancer family history (BCFH), to evaluate if PA is associated with age at thelarche, pubarche and menarche. Maternal-reported questionnaire data measured puberty outcomes, PA in early childhood (ages 3-5 years) and total metabolic equivalents of organized PA in middle childhood (ages 7-9 years). We used interval-censored Weibull parametric survival regression models with age as the time scale and adjusted for sociodemographic factors, and we tested for effect modification by BCFH. We used inverse odds weighting to test for mediation by body mass index-for-age z-score (BMIZ) measured at study enrolment. RESULTS: Being highly active vs inactive in early childhood was associated with later thelarche in girls with a BCFH [adjusted hazard ratio (aHR) = 0.39, 95% CI = 0.26-0.59), but not in girls without a BCFH. In all girls, irrespective of BCFH, being in the highest vs lowest quartile of organized PA in middle childhood was associated with later menarche (aHR = 0.70, 95% CI = 0.50-0.97). These associations remained after accounting for potential mediation by BMIZ. CONCLUSION: This study provides new data that PA in early childhood may be associated with later thelarche in girls with a BCFH, also further supporting an overall association between PA in middle childhood and later menarche.
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Menarca , Puberdade , Feminino , Criança , Pré-Escolar , Humanos , Índice de Massa Corporal , Grupos Raciais , FamíliaRESUMO
Context: Androgen levels are generally measured in serum samples, but urine may be a more feasible option, especially in children, as it is a noninvasive alternative. Objective: To assess the correlations of 10 urinary androgen metabolites with 4 serum androgens [dehydroepiandrosterone-sulfate (DHEA-S), androstenedione, and total and free testosterone] and assess if their correlations differ by participant characteristics. Methods: Our study consisted of 44 girls, ages 6-13, who participated in the New York site of the LEGACY Girls Study and had both serum and urine samples collected at the same visit. We performed Pearson's correlation coefficient tests between 4 serum and 10 individual urinary metabolite measures and their sum. We examined the influence of participant characteristics on the magnitude and direction of the correlations. Results: The summed urinary metabolite measures had the highest correlation with free testosterone in serum (global sum, r = 0.83) and correlated least with DHEA-S in serum (global sum, r = 0.64). The correlation between individual urinary metabolites and serum androgens ranged from 0.08 to 0.84.Two 11-oxygenated urinary metabolites (5α-androstane-3α-ol-11,17-dione5ß-androstane-3α,11ß-diol-17-one) were weakly correlated with all serum androgens. Participant age, weight, height, waist:hip ratio, and pubic hair growth stage changed the correlations between urinary and serum androgens measures between 10% and 213%. Conclusion: The sum of urinary androgen metabolites was a good marker of circulating androstenedione, testosterone, and free testosterone. Individual urinary metabolites provide additional information about the metabolic processes of disease development compared to the antecedent serum androgens.
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PURPOSE: Liver cancer incidence among American Indians/Alaska Natives has risen over the past 20 years. Peripheral blood DNA methylation may be associated with liver cancer and could be used as a biomarker for cancer risk. We evaluated the association of blood DNA methylation with risk of liver cancer. METHODS: We conducted a prospective cohort study in 2324 American Indians, between age 45 and 75 years, from Arizona, Oklahoma, North Dakota and South Dakota who participated in the Strong Heart Study between 1989 and 1991. Liver cancer deaths (n = 21) were ascertained using death certificates obtained through 2017. The mean follow-up duration (SD) for non-cases was 25.1 (5.6) years and for cases, 11.0 (8.8) years. DNA methylation was assessed from blood samples collected at baseline using MethylationEPIC BeadChip 850 K arrays. We used Cox regression models adjusted for age, sex, center, body mass index, low-density lipoprotein cholesterol, smoking, alcohol consumption, and immune cell proportions to examine the associations. RESULTS: We identified 9 CpG sites associated with liver cancer. cg16057201 annotated to MRFAP1) was hypermethylated among cases vs. non-cases (hazard ratio (HR) for one standard deviation increase in methylation was 1.25 (95% CI 1.14, 1.37). The other eight CpGs were hypomethylated and the corresponding HRs (95% CI) ranged from 0.58 (0.44, 0.75) for cg04967787 (annotated to PPRC1) to 0.77 (0.67, 0.88) for cg08550308. We also assessed 7 differentially methylated CpG sites associated with liver cancer in previous studies. The adjusted HR for cg15079934 (annotated to LPS1) was 1.93 (95% CI 1.10, 3.39). CONCLUSIONS: Blood DNA methylation may be associated with liver cancer mortality and may be altered during the development of liver cancer.
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Indígenas Norte-Americanos , Neoplasias Hepáticas , Humanos , Pessoa de Meia-Idade , Idoso , Indígena Americano ou Nativo do Alasca , Metilação de DNA , Estudos Prospectivos , Indígenas Norte-Americanos/genética , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/genéticaRESUMO
The National Institutes of Health's (NIH) Pathways to Prevention panel on postpartum health provides a consensus statement on the evidence, research gaps, and future priorities to prevent maternal morbidity and mortality. The panel reviewed an NIH-commissioned evidence review and workshop that included epidemiologic studies, demonstration interventions, and other maternal morbidity and mortality research to create these national recommendations. The panel concludes that a maternal morbidity and mortality crisis reflects a systemic failure of current U.S. health care, research efforts, and social policies. The panel recommends improving maternal health through a "maternal morbidity and mortality prevention moonshot" that adopts a comprehensive, multilevel life course conceptual framework; strengthens the research methods used within the science of maternal health; establishes and conducts national prevention, treatment, and policy interventions; and reimburses evidence-informed clinical approaches to improve maternal health across the life course. Without a national focus on fundamentally transformative interventions and other initiatives aimed at redressing structural racism and inequities in health care, current interventions and clinical advances in maternal morbidity and mortality prevention will remain tragically insufficient.
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Mortalidade Materna , National Institutes of Health (U.S.) , Feminino , Estados Unidos/epidemiologia , Humanos , Consenso , Medicina Baseada em Evidências , Saúde MaternaRESUMO
Background: People who give care to autistic individuals (autism-caregivers) experience higher levels of caregiver strain than people who provide care for individuals with other chronic conditions (non-autism-caregivers). This places them at higher risk for psychological, behavioural and physical health concerns. The aim of this study is to delineate psychological, behavioural, and physical aspects of caregiver strain in autism-caregivers compared to non-autism-caregivers. Methods: We included 3354 adult caregivers from the general population in the Netherlands participating in the second assessment (January, 1, 2014-December, 31, 2017) of the Lifelines Cohort. In this cohort study, using multivariable regression adjusted for age, sex, and socioeconomic status, we analysed psychological (anxiety and depression based on a Mini International Neuropsychiatric Interview, and self-reported stress and perceived health), behavioural (questionnaire-assessed physical activity, alcohol use, and smoking), and physical aspects (body mass index, waist circumference, and leukocyte-counts) of caregiver strain in autism-caregivers (n = 722) compared with non-autism-caregivers (n = 2632). Findings: Autism-caregivers reported more stress (OR 3.61, 95% CI 2.60-4.99). Both anxiety (OR 1.85, 95% CI 1.37-2.49) and depressive disorders (OR 1.83, 95% CI 1.17-2.86) were more common in autism-caregivers than in non-autism-caregivers. Perceived health, physical activity, alcohol use, and smoking were not different between autism- and non-autism-caregivers. In autism-caregivers, lymphocyte- and monocyte-counts were lower than in non-autism-caregivers. Interpretation: In this large cohort, autism-caregivers had worse psychological health than non-autism-caregivers. Moreover, autism-caregiving might be associated with an altered immune balance. These findings underline the higher caregiver strain in autism-caregivers compared to other caregivers. This calls for increased support to autism-caregivers. Funding: Lifelines has been funded by the Dutch government.
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OBJECTIVE: Women with breast cancer have an increased risk of primary ovarian cancer (BRâOV), and women with ovarian cancer have an increased risk of primary breast cancer (OVâBR). This systematic review summarizes risk factors for developing BRâOV and OVâBR. METHODS: We searched PubMed and Embase until June 2022. RESULTS: We identified 23 articles meeting our inclusion criteria. Studies observed a lower risk of BRâOV for Black versus White women, alcohol consumption, radiotherapy and hormone therapy, BRCA2 versus BRCA1, and ER/PR positive versus negative breast tumors, and a higher risk with family history of breast/ovarian cancer, triple negative versus luminal breast cancer, and higher grade breast tumors. There was an increased risk of OVâBR with family history of cancer. CONCLUSIONS: Tumor characteristics, and genetic and familial factors are associated with risk of BRâOV and OVâBR. These results could aid clinicians in decision-making for breast and ovarian cancer patients, including risk-reducing strategies.
Assuntos
Neoplasias da Mama , Neoplasias Ovarianas , Feminino , Humanos , Mutação , Genes BRCA2 , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Neoplasias da Mama/terapia , Fatores de Risco , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/etiologia , Neoplasias Ovarianas/terapiaRESUMO
PURPOSE: We developed a web-based education intervention as an alternative to predisclosure education with a genetic counselor (GC) to reduce participant burden and provider costs with return of genetic research results. METHODS: Women at three sites who participated in 11 gene discovery research studies were contacted to consider receiving cancer genetic research results. Participants could complete predisclosure education through web education or with a GC. Outcomes included uptake of research results, factors associated with uptake, and patient-reported outcomes. RESULTS: Of 819 participants, 178 actively (21.7%) and 167 passively (20.4%) declined return of results; 474 (57.9%) were enrolled. Most (60.3%) received results although this was lower than the 70% uptake we hypothesized. Passive and active decliners were more likely to be Black, to have less education, and to have not received phone follow-up after the invitation letter. Most participants selected web education (88.5%) as an alternative to speaking with a GC, but some did not complete or receive results. Knowledge increased significantly from baseline to other time points with no significant differences between those who received web versus GC education. There were no significant increases in distress between web and GC education. CONCLUSION: Interest in web-based predisclosure education for return of genetic research results was high although it did not increase uptake of results. We found no negative patient-reported outcomes with web education, suggesting that it is a viable alternative delivery model for reducing burdens and costs of returning genetic research results. Attention to attrition and lower uptake of results among Black participants and those with less formal education are important areas for future research.