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1.
Diabetes Care ; 44(3): 707-714, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33419931

RESUMO

OBJECTIVE: The empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory pattern (EDIP) scores assess the insulinemic and inflammatory potentials of habitual dietary patterns, irrespective of the macronutrient content, and are based on plasma insulin response or inflammatory biomarkers, respectively. The glycemic index (GI) and glycemic load (GL) assess postprandial glycemic potential based on dietary carbohydrate content. We tested the hypothesis that dietary patterns promoting hyperinsulinemia, chronic inflammation, or hyperglycemia may influence type 2 diabetes risk. RESEARCH DESIGN AND METHODS: We calculated dietary scores from baseline (1993-1998) food frequency questionnaires among 73,495 postmenopausal women in the Women's Health Initiative, followed through March 2019. We used multivariable-adjusted Cox regression to estimate hazard ratios (HRs) and 95% CIs for type 2 diabetes risk. We also estimated multivariable-adjusted absolute risk of type 2 diabetes. RESULTS: During a median 13.3 years of follow-up, 11,009 incident cases of type 2 diabetes were diagnosed. Participants consuming the most hyperinsulinemic or proinflammatory dietary patterns experienced greater risk of type 2 diabetes; HRs (95% CI) comparing highest to lowest dietary index quintiles were EDIH 1.49 (1.32-1.68; P trend < 0.0001) and EDIP 1.45 (1.29-1.63; P trend < 0.0001). The absolute excess incidence for the same comparison was 220 (EDIH) and 271 (EDIP) cases per 100,000 person-years. GI and GL were not associated with type 2 diabetes risk: GI 0.99 (0.88-1.12; P trend = 0.46) and GL 1.01 (0.89-1.16; P trend = 0.30). CONCLUSIONS: Our findings in this diverse cohort of postmenopausal women suggest that lowering the insulinemic and inflammatory potentials of the diet may be more effective in preventing type 2 diabetes than focusing on glycemic foods.

2.
Cancer ; 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33476042

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) has a high recurrence risk and poor clinical outcomes. Associations between metabolic syndrome (MetS) risk components and mortality in postmenopausal women with TNBC were examined in the Women's Health Initiative. METHODS: Five hundred forty-four postmenopausal women were diagnosed with nonmetastatic TNBC. Baseline risk components included a high waist circumference (≥88 cm), high blood pressure, hypercholesterolemia, and diabetes. Groups were categorized by the number of MetS risk components: none, 1 or 2, or 3 or 4. Hazard ratios (HRs) and 95% confidence intervals (CIs) across groups were computed with multivariable adjusted Cox models. Outcomes included breast cancer-specific mortality and breast cancer overall mortality (breast cancer followed by death from any cause). Variables in the multivariable model included age at TNBC diagnosis; race/ethnicity; income; education; clinical/observational trial status; history of oral contraceptive, hormone, and/or statin use; cancer stage; and chemotherapy and/or radiation treatment status. RESULTS: Of the 544 participants with TNBC, 33% had no MetS risk components (n = 178), 59% had 1 or 2 risk components (n = 323), and 8% had 3 or 4 risk components (n = 43). After a median follow-up from diagnosis of 8.3 years, multivariable results showed that women with 3 or 4 risk components had a nonsignificantly higher risk of breast cancer mortality (HR, 2.05; 95% CI, 0.94-4.47 trend P = .114) and a significantly higher risk of overall mortality (HR, 2.13; 95% CI, 1.22-3.71; trend P = .006) versus women with 0 risk components. CONCLUSIONS: Postmenopausal women with TNBC and 3 or 4 MetS risk components have a nonsignificantly higher breast cancer mortality risk and a significantly higher overall mortality risk, likely because of negative influences of metabolic risk factors on several causes of death.

3.
BMC Med Genet ; 21(1): 228, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33213418

RESUMO

BACKGROUND: Though bladder cancer has been the subject of many well-powered genome-wide association studies, the mechanisms involving bladder-cancer-associated single nucleotide polymorphisms (SNPs) remain largely unknown. This study focuses on rs798766, rs401681, rs2294008, and rs8102137, which have been associated with bladder cancer and are also cis-acting methylation quantitative loci (mQTL). METHODS: Among 412 bladder cancer cases and 424 controls from the Women's Health Initiative (WHI), we assessed whether the effects of these SNPs on bladder cancer are mediated through proximal DNA methylation changes in pre-diagnostic blood at mQTL-associated CpG sites, which we refer to as natural indirect effects (NIEs). We used a multiple-mediator mediation model for each of the four mQTL adjusted for matching variables and potential confounders, including race/ethnicity, smoking status, and pack-years of smoking. RESULTS: While not statistically significant, our results suggest that substantial proportions of the modest effects of rs401681 (ORNIE = 1.05, 95% confidence interval (CI) = 0.89 to 1.25; NIE percent = 98.5%) and rs2294008 (ORNIE = 1.10, 95% CI = 0.90 to 1.33; NIE percent = 77.6%) on bladder cancer risk are mediated through differential DNA methylation at nearby mQTL-associated CpG sites. The suggestive results indicate that rs2294008 may affect bladder cancer risk through a set of genes in the lymphocyte antigen 6 family, which involves genes that bind to and modulate nicotinic acetylcholine receptors. There was no suggestive evidence supporting mediation for rs8102137 and rs798766. CONCLUSIONS: Though larger studies are necessary, the methylation changes associated with rs401681 and rs2294008 at mQTL-associated CpG sites may be relevant for bladder carcinogenesis, and this study demonstrates how multi-omic data can be integrated to help understand the downstream effects of genetics variants.

4.
Ann Epidemiol ; 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32805399

RESUMO

PURPOSE: Personality traits have been reported to be associated with type 2 diabetes (T2DM) risk. The objective of this study was to examine whether and to what extent the associations between personality traits (dispositional optimism, hostility, and negative emotional expressiveness) and risk of T2DM were mediated by health behaviors and obesity. METHODS: Postmenopausal women (n = 110,992) aged 50-79 years without diabetes at enrollment in the Women's Health Initiative study (1993-1998) were followed up to 25 years. Incident diabetes was assessed via a validated self-report of physician-diagnosed diabetes treated with insulin or other hypoglycemic medications. Mediation analyses were performed using approaches under a counterfactual framework. RESULTS: An inverse association of optimism with diabetes was significantly mediated by a factor primarily extracted from physical activity, diet quality, and sleep quality with a mediated proportion of 28%. Positive associations for hostility and negative emotional expressiveness were substantially mediated by a factor primarily composed of body mass index and waist circumference with mediated proportions of 32% and 44%, respectively. CONCLUSIONS: Our data revealed that less than half of the associations between personality traits and risk of T2DM were explained by indirect health behavior pathways. Women's personality traits should be considered in prevention of diabetes in addition to promoting health behaviors.

5.
Int J Cancer ; 147(10): 2717-2724, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32390249

RESUMO

Physical activity is associated with decreased risk for many cancers. Studies on the association between physical activity and risk of bladder cancer are limited, and findings are inconsistent. Postmenopausal women (mean age = 63.3) were recruited into the Women's Health Initiative from 1993 to 1998. Self-reported baseline information on physical activity and other covariates were available in 141 288 participants. Incident bladder cancer cases were collected through 2018 and centrally adjudicated. Hazard ratios (HRs) and 95% confidence intervals (CIs) were determined by Cox proportional hazard regression models. Effect modification due to smoking was assessed. During an average of 18.5 years of follow-up, 817 bladder cancer cases were identified. Compared to physically inactive women, those who engaged in ≥15 MET-hours/week of total physical activity, ≥8.75 MET-hours/week of walking or ≥11.25 MET-hours/week of moderate to vigorous physical activity had lower risk of bladder cancer (HR = 0.74, 95% CI: 0.59-0.94, P for linear trend = .02; HR = 0.79, 95% CI: 0.63-0.98, P for linear trend = .03; and HR = 0.76, 95% CI: 0.61-0.94, P for linear trend = .02, respectively). No effect modification was found by smoking status (P for interaction = .06, 0.91 and 0.27, respectively). We found that total physical activity, walking and moderate to vigorous physical activity were inversely associated with bladder cancer incidence among postmenopausal women in a dose-response manner. Physical activity may play a potential role in the primary prevention of bladder cancer. Further studies with objective measurements of physical activity are needed to confirm these findings.

6.
Cancer Med ; 9(10): 3563-3573, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32207560

RESUMO

BACKGROUND: Body mass index (BMI) and diabetes are established risk factors for colorectal cancer (CRC), likely through perturbations in metabolic traits (e.g. insulin resistance and glucose homeostasis). Identification of interactions between variation in genes and these metabolic risk factors may identify novel biologic insights into CRC etiology. METHODS: To improve statistical power and interpretation for gene-environment interaction (G × E) testing, we tested genetic variants that regulate expression of a gene together for interaction with BMI (kg/m2 ) and diabetes on CRC risk among 26 017 cases and 20 692 controls. Each variant was weighted based on PrediXcan analysis of gene expression data from colon tissue generated in the Genotype-Tissue Expression Project for all genes with heritability ≥1%. We used a mixed-effects model to jointly measure the G × E interaction in a gene by partitioning the interactions into the predicted gene expression levels (fixed effects), and residual G × E effects (random effects). G × BMI analyses were stratified by sex as BMI-CRC associations differ by sex. We used false discovery rates to account for multiple comparisons and reported all results with FDR <0.2. RESULTS: Among 4839 genes tested, genetically predicted expressions of FOXA1 (P = 3.15 × 10-5 ), PSMC5 (P = 4.51 × 10-4 ) and CD33 (P = 2.71 × 10-4 ) modified the association of BMI on CRC risk for men; KIAA0753 (P = 2.29 × 10-5 ) and SCN1B (P = 2.76 × 10-4 ) modified the association of BMI on CRC risk for women; and PTPN2 modified the association between diabetes and CRC risk in both sexes (P = 2.31 × 10-5 ). CONCLUSIONS: Aggregating G × E interactions and incorporating functional information, we discovered novel genes that may interact with BMI and diabetes on CRC risk.

7.
J Cent Nerv Syst Dis ; 12: 1179573519899471, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32009828

RESUMO

Background and rationale: Stroke is considered the most common cause of adult disability. Intensive rehabilitation protocols outperform nonintensive counterparts. The subacute stroke phase represents a potential window to recovery. Virtual reality (VR) has been shown to provide a more stimulating environment, allowing for increased patient compliance. However, the quality of current literature comparing VR with standard therapies is limited. Our aim is to measure the impact of VR versus standard therapy on the recovery of the upper limb motor function in patients with stroke in the early subacute recovery phase. Method: This is a randomized, controlled trial that will assign 262 patients to tailor-made standard rehabilitation (TMSR) or TMSR plus immersive VR device. The trial will be conducted in an urban rehabilitation clinic in the United States with expertise in the management of poststroke patients. Patients will be 18 to 70 years of age and in the early subacute period (30-90 days post ischemic stroke). The primary outcome will be the change of Fugl-Meyer Assessment-Upper Extremity (FMA-UE) score, measured at baseline and 13 weeks after randomization. The secondary outcome will be the change in the UK Functional Independence Measure and Functional Assessment Measure (UK FIM-FAM) score at the same time points. Discussion: If the use of VR in the rehabilitation of patients with stroke proves to have a significant impact on their motor recovery, it will constitute an extremely important step into decreasing the functional impairment associated with stroke and the related health care expense burden.

8.
Genes (Basel) ; 11(1)2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31947684

RESUMO

Type 2 diabetes mellitus (T2DM) is a common polygenic disease with associated comorbidities. Obesity is a major risk factor for the development of T2DM. The aim of this study is to determine the allele and genotype frequency of peroxisome proliferator-activated receptor-γ (PPARγ) rs1801282, fat mass and obesity-associated protein (FTO) rs9939609, and melanocortin 4 receptor (MC4R) rs2229616 polymorphisms and their association with risk of T2DM in the western Saudi population as mediators of adiposity phenotypes. In a cross-sectional prospective study, genomic DNA from control and T2DM patients were isolated and genotyped for these single-nucleotide polymorphisms. There was a significant association of the MC4R rs2229616 variant with T2DM, but no association with T2DM was detected with PPARγ rs1801282 or FTO rs9939609. The combination of C/C for PPARγ rs1801282, A/A for FTO rs9939609, and C/C for MC4R rs2229616 increased the risk of T2DM by 1.82. The A/T genotype for FTO rs9939609 was predicted to decrease the risk of T2DM when combined with C/C for PPARγ rs1801282 and C/C for MC4R rs2229616 or C/C for PPARγ rs1801282 and C/T MC4R rs2229616. In conclusion, our study showed the risk of the assessed variants for the development of T2DM in the Saudi population.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Diabetes Mellitus Tipo 2/genética , PPAR gama/genética , Receptor Tipo 4 de Melanocortina/genética , Adiposidade , Adulto , Alelos , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , Índice de Massa Corporal , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Variação Genética/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/genética , PPAR gama/metabolismo , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Estudos Prospectivos , Receptor Tipo 4 de Melanocortina/metabolismo , Fatores de Risco , Arábia Saudita/epidemiologia
9.
Cancer Epidemiol Biomarkers Prev ; 29(3): 591-598, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31915146

RESUMO

BACKGROUND: Obesity-related cancers disproportionately affect the Black community. We assessed the relationship between diet quality, physical activity, and their combined effect on obesity-related cancer risk and mortality in Black women enrolled in the Women's Health Initiative (WHI). METHODS: Data from postmenopausal (50-79 years of age) Black women enrolled in WHI clinical trials or observational studies were analyzed. Exposure variables included baseline physical activity [metabolic equivalent of tasks (MET)-hours/week of moderate-to-vigorous physical activity (MVPA)] and diet quality [Healthy Eating Index (HEI)-2015]. Outcomes included adjudicated obesity-related cancer incidence and mortality. Cox proportional hazard models were used to evaluate the association between MVPA and HEI-2015 and obesity-related cancer risk and mortality. RESULTS: The analytical sample included 9,886 Black women, with a baseline mean body mass index (BMI) of 31.1 kg/m2 (SD = 6.8); mean HEI-2015 score of 63.2 (SD = 11.0, possible range 0 to 100); and mean MVPA of 5.0 (SD = 9.4) MET-hours/week. Over an average of 13 years of follow-up, 950 (9.6%) obesity-related cancer cases were observed, with 313 (32.9%) resulting in death. Physical activity [HR, 1.05; 95% confidence interval (CI), 0.86-1.30], diet quality (HR, 0.99; 95% CI, 0.92-1.08), and their combination (HR, 1.05; 95% CI, 0.85-1.29) were not associated with risk for any or site-specific obesity-related cancers. Similarly, these health behaviors had no association with mortality. CONCLUSIONS: Diet quality, physical activity and their combined effect, as measured, were not associated with obesity-related cancer risk and mortality in Black women enrolled in WHI. IMPACT: Other social, behavioral, and biological factors may contribute to racial disparities observed in obesity-related cancer rates.

10.
Cancer ; 126(8): 1766-1775, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-31972054

RESUMO

BACKGROUND: We evaluated associations between perceived social support, social integration, living alone, and colorectal cancer (CRC) outcomes in postmenopausal women. METHODS: The study included 1431 women from the Women's Health Initiative who were diagnosed from 1993 through 2017 with stage I through IV CRC and who responded to the Medical Outcomes Study Social Support survey before their CRC diagnosis. We used proportional hazards regression to evaluate associations of social support (tertiles) and types of support, assessed up to 6 years before diagnosis, with overall and CRC-specific mortality. We also assessed associations of social integration and living alone with outcomes also in a subset of 1141 women who had information available on social ties (marital/partner status, community and religious participation) and living situation. RESULTS: In multivariable analyses, women with low (hazard ratio [HR], 1.52; 95% CI, 1.23-1.88) and moderate (HR, 1.21; 95% CI, 0.98-1.50) perceived social support had significantly higher overall mortality than those with high support (P [continuous] < .001). Similarly, women with low (HR, 1.42; 95% CI, 1.07-1.88) and moderate (HR, 1.28; 95% CI, 0.96-1.70) perceived social support had higher CRC mortality than those with high social support (P [continuous] = .007). Emotional, informational, and tangible support and positive interaction were all significantly associated with outcomes, whereas affection was not. In main-effects analyses, the level of social integration was related to overall mortality (P for trend = .02), but not CRC mortality (P for trend = .25), and living alone was not associated with mortality outcomes. However, both the level of social integration and living alone were related to outcomes in patients with rectal cancer. CONCLUSIONS: Women with low perceived social support before diagnosis have higher overall and CRC-specific mortality.


Assuntos
Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/psicologia , Pós-Menopausa/psicologia , Neoplasias Retais/mortalidade , Neoplasias Retais/psicologia , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Fatores de Risco , Integração Social , Apoio Social , Saúde da Mulher
11.
J Natl Cancer Inst ; 112(2): 170-178, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31184362

RESUMO

BACKGROUND: Insulin resistance has been proposed as a mediator of the increased cancer incidence and mortality associated with obesity. However, prior studies included limited cancer deaths and had inconsistent findings. Therefore, we evaluated insulin resistance and cancer-specific and all-cause mortality in postmenopausal women participating in the Women's Health Initiative (WHI). METHODS: Eligible were a subsample of 22 837 WHI participants aged 50-79 years enrolled at 40 US clinical centers from 1993 to 1998 who had baseline fasting glucose and insulin levels. Baseline insulin resistance was measured by the homeostasis model assessment of insulin resistance (HOMA-IR). Cancers were verified by central medical record review and deaths verified by medical record and death certificate review enhanced by National Death Index queries. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer-specific and all-cause mortality. All statistical tests were two-sided. RESULTS: During a median of 18.9 years of follow-up, 1820 cancer deaths and 7415 total deaths occurred. Higher HOMA-IR quartile was associated with higher cancer-specific mortality (Q4 vs Q1, HR = 1.26, 95% CI = 1.09 to 1.47; Ptrend = .003) and all-cause mortality (Q4 vs Q1, HR = 1.63, 95% CI = 1.51 to 1.76; Ptrend < .001). A sensitivity analysis for diabetes status did not change findings. Among women with body mass index less than 25 kg/m2, higher HOMA-IR quartile was associated with higher cancer mortality (Fine and Gray, P = .004). CONCLUSIONS: High insulin resistance, as measured by HOMA-IR, identifies postmenopausal women at higher risk for cancer-specific and all-cause mortality who could potentially benefit from early intervention.


Assuntos
Causas de Morte , Resistência à Insulina , Neoplasias/epidemiologia , Pós-Menopausa , Saúde da Mulher , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Neoplasias/mortalidade , Modelos de Riscos Proporcionais , Vigilância em Saúde Pública , Fatores de Risco , Estados Unidos/epidemiologia
12.
Menopause ; 26(12): 1385-1394, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31567871

RESUMO

OBJECTIVE: The aim of the study was to develop a web-based calculator that predicts the likelihood of experiencing multiple, competing outcomes prospectively over 5, 10, and 15 years. METHODS: Baseline demographic and medical data from a healthy and racially and ethnically diverse cohort of 161,808 postmenopausal women, aged 50 to 79 at study baseline, who participated in the Women's Health Initiative (WHI), were used to develop and evaluate a risk-prediction calculator designed to predict individual risk for morbidity and mortality outcomes. Women were enrolled from 40 sites arranged in four regions of the United States. The calculator predicts all-cause mortality, adjudicated outcomes of health events (ie, myocardial infarction [MI], stroke, and hip fracture), and disease (lung, breast, and colorectal cancer). A proportional subdistribution hazards regression model was used to develop the calculator in a training dataset using data from three regions. The calculator was evaluated using the C-statistic in a test dataset with data from the fourth region. RESULTS: The predictive validity of our calculator measured by the C-statistic in the test dataset for a first event at 5 and 15 years was as follows: MI 0.77, 0.61, stroke 0.77, 0.72, lung cancer 0.82, 0.79, breast cancer 0.60, 0.59, colorectal cancer 0.67, 0.60, hip fracture 0.79, 0.76, and death 0.74, 0.72. CONCLUSION: This study represents the first large-scale study to develop a risk prediction calculator that yields health risk prediction for several outcomes simultaneously. Development of this tool is a first step toward enabling women to prioritize interventions that may decrease these risks. : Video Summary:http://links.lww.com/MENO/A463.


Assuntos
Nível de Saúde , Mortalidade/tendências , Pós-Menopausa/fisiologia , Medição de Risco/métodos , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Saúde da Mulher
13.
Mol Clin Oncol ; 11(3): 252-258, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31423310

RESUMO

The anticarcinogenic effect of statins may reduce the metastatic potential of cancer cells leading to 'stage migration', with users more likely diagnosed with early rather than late stage cancer. The association between prior statin use and colorectal cancer (CRC) stage at diagnosis in the Women's Health Initiative (WHI) was investigated. The study population included 132,322 post-menopausal women, among which there were 2,628 pathologically confirmed cases of in situ (3.3%), localized (43.6%), regional (40.4%) and distant (12.7%) stage CRC, after an average of 13.9 (SD=4.7) years of follow-up. To reduce the possibility of detection bias among women more likely to be prescribed statins, women who did not report a mammogram within 5 years of study entry and who had no health insurance or medical care provider (n=28,237) were excluded from the study. Stage was coded using SEER criteria into early (in situ and local) vs. late (regional and distant) stage disease. Hazards ratios (HR) and 95% confidence intervals (CIs) evaluating the association between statin use and diagnosis of late-stage CRC both at baseline and in a time-dependent manner were computed from multivariable-adjusted Cox proportional hazards analyses. In the multivariable time-dependent analysis, there was a lower hazard of late stage CRC among users of lipophilic statins compared with non-users (HR=0.80, 95% CI 0.66-0.98, P=0.029) and a marginally lower hazard of late stage CRC among users of lipophilic vs. hydrophilic statins (HR=0.70, 95% CI 0.49-1.01, P=0.058). The use of lipophilic statins was associated with a reduction in the proportion of CRC cases that were late stage at the time of diagnosis.

14.
J Epidemiol Community Health ; 73(9): 888-892, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31289118

RESUMO

BACKGROUND: Bone loss is a major public health concern with large proportions of older women experiencing osteoporotic fractures. Previous research has established a relationship between psychosocial stressors and fractures. However, few studies have investigated bone loss as an intermediary in this relationship. This study investigates whether social stress is associated with bone loss during a 6-year period in postmenopausal women. METHODS: Data from 11 020 postmenopausal women from the USA was used to examine self-reported psychosocial stress in relation to change in bone mineral density (BMD) measured at the femoral neck, lumbar spine and total hip. Linear regression models were used to examine associations between social measures of psychosocial stress (social strain, social functioning and social support) and per cent change in BMD over 6 years. RESULTS: High social stress was associated with decreased BMD over 6 years. After adjustment for confounders, each point higher in social strain was associated with 0.082% greater loss of femoral neck BMD, 0.108% greater loss of total hip BMD and 0.069% greater loss of lumbar spine BMD (p<0.05). Low social functioning and low social support were associated with greater decreases in femoral neck BMD, and low social functioning was associated with greater decreases in total hip BMD. CONCLUSION: The findings provide evidence for an association between high social stress and greater bone loss over 6 years of follow-up. In agreement with the prior literature, the findings for social strain and social functioning suggest that poor quality of social relationships may be associated with bone loss in postmenopausal women.

15.
Stroke ; 50(4): 797-804, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30869565

RESUMO

Background and Purpose- In the United States, black Americans exhibit a greater risk of stroke and burden of stroke risk factors than whites; however, it is unclear whether these stroke risk factors influence stroke risk differently across racial groups. Methods- In total, 126 018 participants of the Women's Health Initiative (11 389 black and 114 629 white women), free of stroke and coronary heart disease at baseline (1994-1998), were followed through 2010. Participants completed baseline clinical exams with standardized measurements of blood pressure and anthropometrics, medication inventory and self-reported questionnaires on sociodemographics, behaviors/lifestyle, and medical history. Incident total, ischemic and hemorrhagic strokes were updated annually through questionnaires with medical record confirmation. Rate differences (per 100 000 person-years) and hazard ratios (HR) based on multivariable Cox models and were estimated. Results- Over a median of 13 years, 4344 stroke events were observed. Absolute incidence rates were higher in black than white women in each age group. In age-adjusted analyses, the risk of stroke was significantly higher among black compared with white women (HR=1.47, 95% CI, 1.33-1.63); adjustment for stroke risk factors, which may be on the causal pathway, attenuated the estimate. Racial disparities were greatest among women 50 to <60 years (HR=3.48; 95% CI, 2.31-5.26; rate difference =99) and diminished with increasing age (60 to <70 HR=1.80; 95% CI, 1.50-2.16; rate difference =107; ≥70 years: HR=1.26; 95% CI, 1.10-1.43; rate difference =87; Pinteraction <0.001). Black women 50 to <60 years remained at significantly higher risk than white women after adjustment for stroke risk factors (HR=1.76; 95% CI, 1.09-2.83). Conclusions- There was a moderately greater risk of total stroke among black compared with white women; however, racial disparities were greatest among women aged 50 to <60 years. Interventions targeted at younger black women may provide the greatest benefit in reducing disparities.


Assuntos
Afro-Americanos/estatística & dados numéricos , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Acidente Vascular Cerebral/epidemiologia , Grupo com Ancestrais do Continente Africano/estatística & dados numéricos , Idoso , Pressão Sanguínea , Feminino , Humanos , Incidência , Estudos Longitudinais , Pessoa de Meia-Idade , Fatores de Risco , Acidente Vascular Cerebral/etnologia , Estados Unidos/epidemiologia
16.
Menopause ; 26(6): 629-636, 2019 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-30672885

RESUMO

OBJECTIVE: We examined whether personality traits, including optimism, ambivalence over emotional expressiveness, negative emotional expressiveness, and hostility, were associated with risk of developing type 2 diabetes (hereafter diabetes) among postmenopausal women. METHODS: A total of 139,924 postmenopausal women without diabetes at baseline (between 1993 and 1998) aged 50 to 79 years from the Women's Health Initiative were prospectively followed for a mean of 14 (range 0.1-23) years. Multivariable Cox proportional hazards regression models were used to assess associations between personality traits and diabetes incidence adjusting for common demographic factors, health behaviors, and depressive symptoms. Personality traits were gathered at baseline using questionnaires. Diabetes during follow-up was assessed via self-report of physician-diagnosed treated diabetes. RESULTS: There were 19,240 cases of diabetes during follow-up. Compared with women in the lowest quartile of optimism (least optimistic), women in the highest quartile (most optimistic) had 12% (hazard ratio [HR], 0.88; 95% confidence interval [CI]: 0.84-0.92) lower risk of incident diabetes. Compared with women in the lowest quartile for negative emotional expressiveness or hostility, women in the highest quartile had 9% (HR, 1.09; 95% CI: 1.05-1.14) and 17% (HR, 1.17; 95% CI: 1.12-1.23) higher risk of diabetes, respectively. The association of hostility with risk of diabetes was stronger among nonobese than obese women. CONCLUSIONS: Low optimism and high NEE and hostility were associated with increased risk of incident diabetes among postmenopausal women independent of major health behaviors and depressive symptoms. In addition to efforts to promote healthy behaviors, women's personality traits should be considered to guide clinical or programmatic intervention strategies in diabetes prevention.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Personalidade/fisiologia , Pós-Menopausa/psicologia , Idoso , Idoso de 80 Anos ou mais , Depressão , Feminino , Seguimentos , Comportamentos Relacionados com a Saúde , Humanos , Incidência , Pessoa de Meia-Idade , Prevalência , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Autorrelato , Estados Unidos/epidemiologia , Saúde da Mulher
17.
JAMA Oncol ; 5(2): 155-163, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30520976

RESUMO

Importance: Obesity is associated with an increased risk of breast cancer, including the estrogen receptor (ER)-positive subtype in postmenopausal women. Whether excess adiposity is associated with increased risk in women with a normal body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is unknown. Objective: To investigate the association between body fat and breast cancer risk in women with normal BMI. Design, Setting, and Participants: This ad hoc secondary analysis of the Women's Health Initiative (WHI) clinical trial and observational study cohorts was restricted to postmenopausal participants with a BMI ranging from 18.5 to 24.9. Women aged 50 to 79 years were enrolled from October 1, 1993, through December 31, 1998. Of these, 3460 participants underwent body fat measurement with dual-energy x-ray absorptiometry (DXA) at 3 US designated centers with follow-up. At a median follow-up of 16 years (range, 9-20 years), 182 incident breast cancers had been ascertained, and 146 were ER positive. Follow-up was complete on September 30, 2016, and data from October 1, 1993, through September 30, 2016, was analyzed August 2, 2017, through August 21, 2018. Main Outcomes and Measures: Body fat levels were measured at baseline and years 1, 3, 6, and 9 using DXA. Information on demographic data, medical history, and lifestyle factors was collected at baseline. Invasive breast cancers were confirmed via central review of medical records by physician adjudicators. Blood analyte levels were measured in subsets of participants. Results: Among the 3460 women included in the analysis (mean [SD] age, 63.6 [7.6] years), multivariable-adjusted hazard ratios for the risk of invasive breast cancer were 1.89 (95% CI, 1.21-2.95) for the highest quartile of whole-body fat and 1.88 (95% CI, 1.18-2.98) for the highest quartile of trunk fat mass. The corresponding adjusted hazard ratios for ER-positive breast cancer were 2.21 (95% CI, 1.23-3.67) and 1.98 (95% CI, 1.18-3.31), respectively. Similar positive associations were observed for serial DXA measurements in time-dependent covariate analyses. Circulating levels of insulin, C-reactive protein, interleukin 6, leptin, and triglycerides were higher, whereas levels of high-density lipoprotein cholesterol and sex hormone-binding globulin were lower in those in the uppermost vs lowest quartiles of trunk fat mass. Conclusions and Relevance: In postmenopausal women with normal BMI, relatively high body fat levels were associated with an elevated risk of invasive breast cancer and altered levels of circulating metabolic and inflammatory factors. Normal BMI categorization may be an inadequate proxy for the risk of breast cancer in postmenopausal women. Trial Registration: ClinicalTrials.gov identifier: NCT00000611.


Assuntos
Adiposidade , Índice de Massa Corporal , Neoplasias da Mama/epidemiologia , Pós-Menopausa , Idoso , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/fisiopatologia , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Estados Unidos/epidemiologia , Saúde da Mulher
18.
J Gerontol A Biol Sci Med Sci ; 74(12): 1952-1958, 2019 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-30590438

RESUMO

BACKGROUND: Women comprise nearly half of the labor force in our society, but the impact of the occupational psychical activity on women's heart health in later life was unclear. We conducted a case-cohort study to assess the association of occupational physical activity (OPA), alone and jointly with leisure-time physical activity (LTPA) and risk of coronary heart disease (CHD). METHODS: We included women enrolled in Women's Health Initiative Observational Study who provided an occupational history at baseline and were followed until 2013 for the first occurrence of myocardial infarction or death from CHD (mean age ± SD = 63.4 ± 7.2). A total of 5,243 women free of CHD at baseline were randomly selected into a subcohort and 3,421 CHD events were adjudicated during follow-up. Through linkage of Standard Occupational Classification codes to the Occupational Information Network, we assessed cumulative and most recent exposure of OPA. LTPA was assessed through Women's Health Initiative's physical activity questionnaire. Weighted Cox proportional hazard models were used to evaluate CHD risk. RESULTS: After adjustment for demographic and socioeconomic factors, levels of OPA were not associated with CHD risk. Compared with women with low OPA and high LTPA, women with moderate to high cumulative OPA and low LTPA had relative high CHD risk (hazard ratio [HR]: 1.54, 95% confidence interval [CI]: 1.26, 1.88 for moderate OPA and HR: 1.46. 95% CI: 1.20, 1.78 for high OPA). DISCUSSION: Results from this study suggest no overall association between lifetime OPA and CHD risk in women, but the impact of OPA varies by LTPA levels.


Assuntos
Doença das Coronárias/epidemiologia , Exercício Físico , Ocupações , Idoso , Doença das Coronárias/mortalidade , Feminino , Humanos , Atividades de Lazer , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários , Estados Unidos/epidemiologia , Saúde da Mulher
19.
PLoS One ; 13(10): e0206519, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30379922

RESUMO

BACKGROUND: High levels of serum leptin and low levels of serum adiponectin are strongly correlated with obesity, a well-established risk factor for colorectal cancer (CRC). Growing evidence suggests that dysregulation of leptin and adiponectin levels may play an etiological role in colorectal carcinogenesis. We evaluated 20 candidate variants in 4 genes previously shown to alter serum leptin and adiponectin levels for associations with obesity (BMI>30 kg/m2) and CRC risk. METHODS: We analyzed 6,246 CRC cases and 7,714 population-based controls from 11 studies within the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Associations of each variant with obesity or CRC were evaluated using multivariate logistic regression models stratified by sex and adjusted for age, a study variable, and the first three principal components of genetic ancestry. Gene-specific False Discovery Rate (FDR)-adjusted p-values <0.05 denoted statistical significance. RESULTS: Two variants in the leptin gene showed statistically significant associations with CRC among women: LEP rs2167270 (OR = 1.13, 95% CI: 1.06-1.21) and LEP rs4731426 (OR = 1.09, 95% CI: 1.02-1.17). These associations remained significant after adjustment for obesity, suggesting that leptin SNPs may influence CRC risk independent of obesity. We observed statistically significant interactions of the leptin variants with hormone replacement therapy (HRT) for CRC risk; these variant associations were strengthened when analyses were restricted to post-menopausal women with low estrogen exposure, as estimated by 'never use' of HRT and/or non-obese BMI. No variants were associated with CRC among men. CONCLUSIONS: Leptin gene variants may exhibit sex-specific associations with CRC risk. Endogenous and exogenous estrogen exposure may modify the association between these variants, leptin levels, and CRC risk.


Assuntos
Neoplasias Colorretais/genética , Predisposição Genética para Doença , Leptina/genética , Polimorfismo de Nucleotídeo Único , Adiponectina/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Neoplasias Colorretais/patologia , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Fatores Sexuais
20.
Hum Genet ; 137(10): 795-806, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30267214

RESUMO

Although ~ 25% of colorectal cancer or polyp (CRC/P) cases show familial aggregation, current germline genetic testing identifies a causal genotype in the 16 major genes associated with high penetrance CRC/P in only 20% of these cases. As there are likely other genes underlying heritable CRC/P, we evaluated the association of variation at novel loci with CRC/P. We evaluated 158 a priori selected candidate genes by comparing the number of rare potentially disruptive variants (PDVs) found in 84 CRC/P cases without an identified CRC/P risk-associated variant and 2440 controls. We repeated this analysis using an additional 73 CRC/P cases. We also compared the frequency of PDVs in select genes among CRC/P cases with two publicly available data sets. We found a significant enrichment of PDVs in cases vs. controls: 20% of cases vs. 11.5% of controls with ≥ 1 PDV (OR = 1.9, p = 0.01) in the original set of cases. Among the second cohort of CRC/P cases, 18% had a PDV, significantly different from 11.5% (p = 0.02). Logistic regression, adjusting for ancestry and multiple testing, indicated association between CRC/P and PDVs in NTHL1 (p = 0.0001), BRCA2 (p = 0.01) and BRIP1 (p = 0.04). However, there was no significant difference in the frequency of PDVs at each of these genes between all 157 CRC/P cases and two publicly available data sets. These results suggest an increased presence of PDVs in CRC/P cases and support further investigation of the association of NTHL1, BRCA2 and BRIP1 variation with CRC/P.


Assuntos
Proteína BRCA2/genética , Neoplasias Colorretais/genética , Desoxirribonuclease (Dímero de Pirimidina)/genética , Proteínas de Grupos de Complementação da Anemia de Fanconi/genética , Loci Gênicos , Variação Genética , RNA Helicases/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
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