JoAnn E Manson

Harvard University, Cambridge, Massachusetts, United States

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Publications (872)9821.71 Total impact

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    ABSTRACT: The repertoire of antigens associated with the development of an autoimmune response in breast cancer has relevance to detection and treatment strategies. We have investigated the occurrence of autoantibodies associated with the development of triple negative breast cancer (TNBC) in the prior to diagnosis setting and in samples collected at the time of diagnosis of TNBC. Lysate arrays containing protein fractions from the TNBC MDA-MB-231 cell line were hybridized with TNBC plasmas from the Women's Health Initiative cohort, collected prior to clinical diagnosis and with plasmas from matched controls. An immune response directed against spliceosome and glycolysis proteins was observed with case plasmas as previously reported in ER+ breast cancer. Importantly autoantibodies directed against networks involving BRCA1, TP53 and cytokeratin proteins associated with a mesenchymal/basal phenotype were distinct to TNBC prior to diagnosis samples. Concordant autoantibody findings were observed with mouse plasma samples collected prior to occurrence of palpable tumors from a C3(1)-T triple negative mouse model. Plasma samples collected at the time of diagnosis of stage II TNBC and from matched healthy controls were subjected to proteomic analysis by mass spectrometry to identify Ig bound proteins yielding a predominance of cytokeratins including several associated with a mesenchymal/basal phenotype among cases compared to controls. Our data provide evidence indicative of a dynamic repertoire of antigens associated with a humoral immune response reflecting disease pathogenesis in TNBC. Copyright © 2015, American Association for Cancer Research.
    Cancer Research 06/2015; DOI:10.1158/0008-5472.CAN-15-0248 · 9.28 Impact Factor
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    ABSTRACT: To examine the putative adverse effects of ambient fine particulate matter (PM2.5 ) on brain volumes in older women. We conducted a prospective study of 1403 community-dwelling older women without dementia enrolled in the Women's Health Initiative Memory Study (WHIMS), 1996-8. Structural brain MRI scans were performed at age of 71-89 years in 2005-6 to obtain volumetric measures of gray matter (GM) and normal-appearing white matter (WM). Given residential histories and air monitoring data, we used a spatiotemporal model to estimate cumulative PM2.5 exposure in 1999-2006. Multiple linear regression was employed to evaluate the associations between PM2.5 and brain volumes, adjusting for intracranial volumes and potential confounders. Older women with greater PM2.5 exposures had significantly smaller WM, but not GM volumes, independent of geographic region, demographics, socioeconomic status, lifestyles, and clinical characteristics including cardiovascular risk factors. For each inter-quartile increment (3.49 µg/m(3) ) of cumulative PM2.5 exposure, the average WM volume (95% confidence interval) was 6.23 (3.72-8.74) cm(3) in the total brain and 4.47 (2.27-6.67) cm(3) lower in the association areas, equivalent to 1-2 years of brain aging. The adverse PM2.5 effects on smaller WM volumes were present in frontal and temporal lobes and corpus callosum (all p-values <0.01). Hippocampal volumes did not differ by PM2.5 exposure. PM2.5 exposure may contribute to WM loss in older women. Future studies are needed to determine whether exposures result in myelination disturbance, disruption of axonal integrity, damages to oligodendrocytes, or other WM neuropathologies. This article is protected by copyright. All rights reserved. © 2015 American Neurological Association.
    Annals of Neurology 06/2015; DOI:10.1002/ana.24460 · 11.91 Impact Factor
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    ABSTRACT: Consistent evidence linking habitual sleep duration with risks of mild cognitive impairment (MCI) and dementia is lacking. We conducted a prospective study on 7444 community-dwelling women (aged 65-80 y) with self-reported sleep duration, within the Women's Health Initiative Memory Study in 1995-2008. Incident MCI/dementia cases were ascertained by validated protocols. Cox models were used to adjust for multiple sociodemographic and lifestyle factors, depression, cardiovascular disease (CVD), and other clinical characteristics. We found a statistically significant (P = .03) V-shaped association with a higher MCI/dementia risk in women with either short (≤6 hours/night) or long (≥8 hours/night) sleep duration (vs. 7 hours/night). The multicovariate-adjusted hazard for MCI/dementia was increased by 36% in short sleepers irrespective of CVD, and by 35% in long sleepers without CVD. A similar V-shaped association was found with cognitive decline. In older women, habitual sleep duration predicts the future risk for cognitive impairments including dementia, independent of vascular risk factors. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 06/2015; DOI:10.1016/j.jalz.2015.03.004 · 17.47 Impact Factor
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    ABSTRACT: Although genome-wide association studies have separately identified many genetic susceptibility loci for ulcerative colitis (UC), Crohn's disease (CD), and colorectal cancer (CRC), there has been no large-scale examination for pleiotropy, or shared genetic susceptibility, for these conditions. We used logistic regression modeling to examine the associations of 181 UC and CD susceptibility variants previously identified by GWAS with risk of CRC using data from the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. We also examined associations of significant variants with clinical and molecular characteristics in a subset of the studies.Among 11,794 CRC cases and 14,190 controls, rs11676348, the susceptibility SNP for UC, was significantly associated with reduced risk of CRC (p = 7E-05). The multivariate-adjusted odds ratio of CRC with each copy of the T allele was 0.93 (95% CI, 0.89-0.96). The association of the SNP with risk of CRC differed according to mucinous histological features (Pheterogeneity=0.008). In addition, the (T) allele was associated with lower risk of tumors with Crohn's-like reaction but not tumors without such immune infiltrate (Pheterogeneity=0.02) and microsatellite instability-high (MSI-high) but not microsatellite stable or MSI-low tumors (Pheterogeneity = 0.03). The minor allele (T) in SNP rs11676348, located downstream from CXCR2 that has been implicated in CRC progression, is associated with a lower risk of CRC, particularly tumors with a mucinous component, Crohn's-like reaction, and MSI-high. Our findings offer the promise of risk stratification of inflammatory bowel disease patients for complications such as CRC. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    Carcinogenesis 06/2015; DOI:10.1093/carcin/bgv086 · 5.27 Impact Factor
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    ABSTRACT: Menopausal hormone therapy (MHT) reportedly increases the risk of cognitive decline in women over age 65 y. It is unknown whether similar risks exist for recently postmenopausal women, and whether MHT affects mood in younger women. The ancillary Cognitive and Affective Study (KEEPS-Cog) of the Kronos Early Estrogen Prevention Study (KEEPS) examined the effects of up to 4 y of MHT on cognition and mood in recently postmenopausal women. KEEPS, a randomized, double-blinded, placebo-controlled clinical trial, was conducted at nine US academic centers. Of the 727 women enrolled in KEEPS, 693 (95.3%) participated in the ancillary KEEPS-Cog, with 220 women randomized to receive 4 y of 0.45 mg/d oral conjugated equine estrogens (o-CEE) plus 200 mg/d micronized progesterone (m-P) for the first 12 d of each month, 211 women randomized to receive 50 μg/d transdermal estradiol (t-E2) plus 200 mg/d m-P for the first 12 d of each month, and 262 women randomized to receive placebo pills and patches. Primary outcomes included the Modified Mini-Mental State examination; four cognitive factors: verbal learning/memory, auditory attention/working memory, visual attention/executive function, and speeded language/mental flexibility; and a mood measure, the Profile of Mood States (POMS). MHT effects were analyzed using linear mixed-effects (LME) models, which make full use of all available data from each participant, including those with missing data. Data from those with and without full data were compared to assess for potential biases resulting from missing observations. For statistically significant results, we calculated effect sizes (ESs) to evaluate the magnitude of changes. On average, participants were 52.6 y old, and 1.4 y past their last menstrual period. By month 48, 169 (24.4%) and 158 (22.8%) of the 693 women who consented for ancillary KEEPS-Cog were lost to follow-up for cognitive assessment (3MS and cognitive factors) and mood evaluations (POMS), respectively. However, because LME models make full use all available data, including data from women with missing data, 95.5% of participants were included in the final analysis (n = 662 in cognitive analyses, and n = 661 in mood analyses). To be included in analyses, women must have provided baseline data, and data from at least one post-baseline visit. The mean length of follow-up was 2.85 y (standard deviation [SD] = 0.49) for cognitive outcomes and 2.76 (SD = 0.57) for mood outcomes. No treatment-related benefits were found on cognitive outcomes. For mood, model estimates indicated that women treated with o-CEE showed improvements in depression and anxiety symptoms over the 48 mo of treatment, compared to women on placebo. The model estimate for the depression subscale was -5.36 × 10-2 (95% CI, -8.27 × 10-2 to -2.44 × 10-2; ES = 0.49, p < 0.001) and for the anxiety subscale was -3.01 × 10-2 (95% CI, -5.09 × 10-2 to -9.34 × 10-3; ES = 0.26, p < 0.001). Mood outcomes for women randomized to t-E2 were similar to those for women on placebo. Importantly, the KEEPS-Cog results cannot be extrapolated to treatment longer than 4 y. The KEEPS-Cog findings suggest that for recently postmenopausal women, MHT did not alter cognition as hypothesized. However, beneficial mood effects with small to medium ESs were noted with 4 y of o-CEE, but not with 4 y of t-E2. The generalizability of these findings is limited to recently postmenopausal women with low cardiovascular risk profiles. ClinicalTrials.gov NCT00154180 and NCT00623311.
    PLoS Medicine 06/2015; 12(6):e1001833. DOI:10.1371/journal.pmed.1001833 · 14.00 Impact Factor
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    ABSTRACT: Importance The use of menopausal hormone therapy (HT) continues in clinical practice, but reports are conflicting concerning the longer-term breast cancer effects of relatively short-term use.Objective To report the longer-term influence of menopausal HT on breast cancer incidence in the 2 Women’s Health Initiative (WHI) randomized clinical trials.Design, Setting, and Participants A total of 27 347 postmenopausal women aged 50 to 79 years were enrolled at 40 US centers from 1993 to 1998 and followed up for a median of 13 years through September 2010.Interventions A total of 16 608 women with a uterus were randomized to conjugated equine estrogens (0.625 mg/d [estrogen]) plus medroxyprogesterone acetate (2.5 mg/d [progestin]) (E + P) or placebo with a median intervention duration of 5.6 years, and 10 739 women with prior hysterectomy were randomized to conjugated equine estrogens alone (0.625 mg/d) or placebo with a median intervention duration of 7.2 years.Main Outcomes and Measures Time-specific invasive breast cancer incidence rates and exploratory analyses of breast cancer characteristics by intervention and postintervention phases in the 2 HT trials.Results In the E + P trial, hazard ratios (HRs) for the influence of combined HT on breast cancer were lower than 1 for 2 years (HR, 0.71; 95% CI, 0.47-1.08) and steadily increased throughout intervention, becoming significantly increased for the entire intervention phase (HR, 1.24; 95% CI, 1.01-1.53). In the early postintervention phase (within 2.75 years from intervention), there was a sharp decrease in breast cancer incidence in the combined HT group, though the HR remained higher than 1 (HR, 1.23; 95% CI, 0.90-1.70). During the late postintervention phase (requiring patient re-consent), the HR for breast cancer risk remained higher than 1 through 5.5 years (median) of additional follow-up (HR, 1.37; 95% CI, 1.06-1.77). In the estrogen alone trial, the HR for invasive breast cancer risk was lower than 1 throughout the intervention phase (HR, 0.79; 95% CI, 0.61-1.02) and remained lower than 1 in the early postintervention phase (HR, 0.55; 95% CI, 0.34-0.89), but risk reduction was not observed during the late postintervention follow-up (HR, 1.17; 95% CI, 0.73-1.87). Characteristics of breast cancers diagnosed during early and late postintervention phases differed in both trials.Conclusions and Relevance In the E + P trial, the higher breast cancer risk seen during intervention was followed by a substantial drop in risk in the early postintervention phase, but a higher breast cancer risk remained during the late postintervention follow-up. In the estrogen alone trial, the lower breast cancer risk seen during intervention was sustained in the early postintervention phase but was not evident during the late postintervention follow-up.
    06/2015; 1(3). DOI:10.1001/jamaoncol.2015.0494
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    ABSTRACT: It is unknown whether supplementation with calcium and vitamin D has an impact on menopause-related symptoms. As part of the Women's Health Initiative Calcium/Vitamin D Supplementation Trial (CaD), women were randomized at 40 clinical sites to elemental calcium carbonate 1000mg with vitamin D 400IU daily or placebo. At the CaD baseline visit (year 1 or year 2) and during a mean follow-up of 5.7 years, participants provided data on menopause-related symptoms via questionnaires. Generalized linear mixed effects techniques were used to address research questions. After excluding participants with missing data (N=2125), we compared menopause-related symptoms at follow-up visits of 17,101 women randomized to CaD with those of 17,056 women given the placebo. Women in the CaD arm did not have a different number of symptoms at follow-up compared to women taking the placebo (p=0.702). Similarly, there was no difference between sleep disturbance, emotional well-being, or energy/fatigue at follow-up in those who were randomized to CaD supplementation compared to those taking the placebo. Our data suggest that supplementation with 1000mg of calcium plus 400IU of vitamin D does not influence menopause-related symptoms over an average of 5.7 years of follow-up among postmenopausal women with an average age of 64 at the WHI baseline visit. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Maturitas 05/2015; 81(3). DOI:10.1016/j.maturitas.2015.04.007 · 2.86 Impact Factor
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    ABSTRACT: The first epigenome-wide association study of body-mass index (BMI) identified DNA methylation at a HIF3A locus associated with BMI. We tested the hypothesis that DNA methylation variants might be associated with BMI according to intake of B vitamins. We analyzed the interaction between DNA methylation variants and B vitamins intake on 10-year change in BMI in two large cohorts. We found significant interactions between the DNA methylation-associated HIF3A SNP rs3826795 and intake of B vitamins on 10-year changes in BMI. The association between rs3826795 and BMI changes consistently increased across the tertiles of total vitamin B2 and B12 intake (all P for interaction <0.01). The differences in the BMI changes per increment of minor allele were -0.10 (SE 0.06), -0.01 (SE 0.06), and 0.12 (SE 0.07) within subgroups defined by increasing tertiles of total vitamin B2 intake; and were -0.10 (SE 0.06), -0.01 (SE 0.06), and 0.10 (SE 0.07) within subgroups defined by increasing tertiles of total vitamin B12 intake. In two independent cohorts, a DNA methylation variant in HIF3A was associated with BMI changes through interactions with total or supplemental vitamin B2, vitamin B12 and folate. These findings suggest a potential causal relation between DNA methylation and adiposity. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
    Diabetes 05/2015; DOI:10.2337/db15-0264 · 8.47 Impact Factor
  • Frank B Hu, Ambika Satija, JoAnn E Manson
    JAMA The Journal of the American Medical Association 05/2015; DOI:10.1001/jama.2015.5287 · 30.39 Impact Factor
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    ABSTRACT: Adiponectin, an adipocyte-secreted hormone, has insulin-sensitizing characteristics. It remains unclear whether adiponectin may influence colorectal cancer development. To determine whether prediagnostic levels of adiponectin were associated with risk of incident colorectal cancer in the Women's Health Study, we conducted a nested case-control study of 275 colorectal cancer cases and 275 matched controls. Each case was matched to a control by age, ethnicity, fasting status at the time of blood collection, time of day when blood was drawn, and month of blood draw. Multivariable logistic regression with adjustment for colorectal cancer risk factors was used to estimate the odds ratio (OR) and 95 % confidence interval (CI) for risk of colorectal cancer incidence and mortality by adiponectin quartiles based on the control distribution. Median plasma adiponectin level was similar in cases versus controls (6.00 vs. 6.24 μg/mL). In multivariable-adjusted logistic regression models, high plasma adiponectin levels were not significantly associated with risk of colorectal cancer [quartile 4 (Q4) vs. quartile 1 (Q1): OR (95 % CI) 0.86 (0.48-1.56), p trend = 0.63]. These results suggest no appreciable association between plasma adiponectin and risk of colorectal cancer in women. Confirmation of these observations in larger studies is needed.
    Cancer Causes and Control 05/2015; 26(7). DOI:10.1007/s10552-015-0590-8 · 2.96 Impact Factor
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    ABSTRACT: To examine the effect of an individually tailored, motivationally matched prenatal exercise intervention on gestational diabetes mellitus (GDM) and other measures of glucose intolerance among ethnically diverse prenatal care patients at increased risk for GDM. The Behaviors Affecting Baby and You study randomized eligible women at a mean (standard deviation) of 18.2 (4.1) weeks of gestation to a 12-week individually tailored, motivationally matched exercise intervention or a comparison health and wellness intervention. The goal of the exercise intervention was to achieve the American College of Obstetricians and Gynecologists' guidelines for physical activity during pregnancy. Diagnosis of GDM, impaired glucose tolerance, abnormal glucose screen, and screening glucose values (mg/dL) were abstracted from medical records. A sample size of 352 women (176 per group) was planned to have 80% power to detect reductions in risk of 35% or larger. From July 2007 to December 2012, a total of 251 (86.5%) women completed the intervention; n=124 and 127 in the exercise and comparison interventions, respectively. Based on an intention-to-treat analysis, no statistically significant differences between the intervention groups were observed; the relative odds of GDM in the exercise group was 0.61 (95% confidence interval [CI] 0.28-1.32) as compared with the health and wellness comparison group. Odds ratios for impaired glucose tolerance and abnormal glucose screen were 0.68 (95% CI 0.35-1.34) and 0.86 (95% CI 0.51-1.47), respectively. The intervention had no effect on birth outcomes. In this randomized trial among ethnically diverse pregnant women at increased risk for GDM, we found that a prenatal exercise intervention implemented in the second trimester did not result in a statistically significant reduction in relative odds for GDM, impaired glucose tolerance, or abnormal glucose screen. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00728377. I.
    Obstetrics and Gynecology 05/2015; 125(5):1195-1204. DOI:10.1097/AOG.0000000000000738 · 4.37 Impact Factor
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    ABSTRACT: Fruit, vegetable, and dietary fiber intake have been associated with lower risk of cardiovascular disease (CVD); however, little is known about their role in obesity prevention. Our goal was to investigate whether intake of fruits, vegetables, and dietary fiber is associated with weight change and the risk of becoming overweight and obese. We studied 18,146 women aged ≥45 y from the Women's Health Study free of CVD and cancer with an initial body mass index (BMI) of 18.5 to <25 kg/m(2). Fruit, vegetable, and dietary fiber intakes were assessed at baseline through a 131-item food-frequency questionnaire, along with obesity-related risk factors. Women self-reported body weight on annual questionnaires. During a mean follow-up of 15.9 y, 8125 women became overweight or obese (BMI ≥25 kg/m(2)). Intakes of total fruits and vegetables, fruits, and dietary fiber were not associated with the longitudinal changes in body weight, whereas higher vegetable intake was associated with greater weight gain (P-trend: 0.02). In multivariable analyses, controlling for total energy intake and physical activity along with other lifestyle, clinical, and dietary factors, women in the highest vs. lowest quintile of fruit intake had an HR of 0.87 (95% CI: 0.80, 0.94; P-trend: 0.01) of becoming overweight or obese. No association was observed for vegetable or dietary fiber intake. The association between fruit intake and risk of becoming overweight or obese was modified by baseline BMI (P-interaction: <0.0001) where the strongest inverse association was observed among women with a BMI <23 kg/m(2) (HR: 0.82; 95% CI: 0.71, 0.94). Our results suggest that greater baseline intake of fruit, but not vegetables or fiber, by middle-aged and older women with a normal BMI at baseline is associated with lower risk of becoming overweight or obese. © 2015 American Society for Nutrition.
    Journal of Nutrition 05/2015; 145(5):960-8. DOI:10.3945/jn.114.199158 · 4.23 Impact Factor
  • Cancer Research 05/2015; 75(9 Supplement):P6-10-04-P6-10-04. DOI:10.1158/1538-7445.SABCS14-P6-10-04 · 9.28 Impact Factor
  • Aruna D Pradhan, JoAnn E Manson
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    ABSTRACT: Despite continued appreciation of the potential role of vitamin D and omega-3 fatty acids in the prevention of cancer and cardiovascular disease (CVD), there remain no completed large-scale, randomized trials of these agents for the primary prevention of cancer or CVD in a population that has not been selected on the basis of elevated risk. The vitamin D and omega-3 trial (VITAL) is a 2×2 factorial randomized, double-blind, placebo-controlled trial of the benefits and risks of vitamin D (vitamin D3 [cholecalciferol], 2000IU/d) and marine omega-3 fatty acids (Omacor(®) fish oil, a 1g/d) in the primary prevention of cancer and CVD among 25,875 men and women, aged ≥50 and ≥55 years, respectively. Randomization began in November 2011 and was completed in March 2014. This report will describe the rationale for the trial and currently available randomized trial data, summarize related ongoing large-scale trials, and provide a brief overview of study design, and an update on randomization milestones, racial/ethnic diversity, biorepository activities, in-depth phenotyping of a subcohort, and ancillary studies. Copyright © 2015. Published by Elsevier Ltd.
    The Journal of steroid biochemistry and molecular biology 04/2015; DOI:10.1016/j.jsbmb.2015.04.006 · 4.05 Impact Factor
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    ABSTRACT: Abdominal obesity is a major risk factor for type 2 diabetes (T2D). We aimed to examine the association between the genetic predisposition to central obesity, assessed by the waist-to-hip ratio (WHR) genetic score, and T2D risk. The current study included 2,591 participants with T2D and 3,052 participants without T2D of European ancestry from the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). Genetic predisposition to central obesity was estimated using a genetic score based on 14 established loci for the WHR. We found that the central obesity genetic score was linearly related to higher T2D risk. Results were similar in the NHS (women) and HPFS (men). In combined results, each point of the central obesity genetic score was associated with an odds ratio (OR) of 1.04 (95% CI, 1.01-1.07) for developing T2D, and the OR was 1.24 (1.03-1.45) when comparing extreme quartiles of the genetic score after multivariate adjustment. The data indicate that genetic predisposition to central obesity is associated with higher T2D risk. This association is mediated by central obesity. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
    Diabetes care 04/2015; DOI:10.2337/dc14-3084 · 8.57 Impact Factor
  • Andrew M Kaunitz, JoAnn E Manson
    Menopause (New York, N.Y.) 04/2015; DOI:10.1097/GME.0000000000000457 · 2.81 Impact Factor
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    ABSTRACT: Results from the Women's Health Initiative (WHI) clinical trials (CT) demonstrated no increase in the risk of lung cancer in postmenopausal women treated with hormone therapy. We conducted a joint analysis of the WHI observational study data and CT data to further explore the association between estrogen and estrogen-related reproductive factors and lung cancer risk. Reproductive history, oral contraceptive (OC) use, and postmenopausal hormone therapy (HT) was evaluated in 160,855 women with known HT exposures. Follow-up for lung cancer was through September 17, 2012; 2,467 incident lung cancer cases were ascertained, with median follow-up of 14 years. For all lung cancers, women with previous use of estrogen plus progestin of < 5 years (HR=0.84; 95% CI 0.71-0.99) were at reduced risk. A limited number of reproductive factors demonstrated associations with risk. There was a trend towards decreased risk with increasing age at menopause (ptrend=0.04) and a trend towards increased risk with increasing number of live births (ptrend=0.03). Reduced risk of non-small cell lung cancer was associated with age 20-29 at first live birth. Risk estimates varied with smoking history, years of HT use and previous bilateral oophorectomy. Indirect measures of estrogen exposure to lung tissue, as used in this study, provide only weak evidence for an association between reproductive history or HT use and risk of lung cancer. More detailed mechanistic studies and evaluation of risk factors in conjunction with ER expression in the lung should continue as a role for estrogen can't be ruled out and may hold potential for prevention and treatment strategies.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 04/2015; DOI:10.1097/JTO.0000000000000558 · 5.80 Impact Factor
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    ABSTRACT: ω3 and ω6 fatty acids (FA) may have divergent effects on the development of obesity. We examined the association of baseline erythrocyte ω3 and ω6 FA composition with body weight change and the risk of becoming overweight or obese in the Women's Health Study (WHS) participants. We identified 534 women who had baseline erythrocyte FA measured and a baseline body mass index (BMI) of 18.5-<25 kg/m(2). Body weight was updated at a total of six time points during follow-up. Weight gain during a mean of 10.4-year follow-up increased with increasing quartiles of baseline erythrocyte cis ω6 FA, ω6/ω3 ratio, and trans FA while decreased with increasing cis ω3 FA. After multivariable adjustment including total energy intake and physical activity, the weight gain (kg) in the highest versus the lowest quartile was 3.08 versus 2.32 for erythrocyte cis ω6 FA (p trend 0.04), 2.07 versus 2.92 for cis ω3 FA (p trend 0.08), 2.93 versus 2.05 for ω6/ω3 ratio (p trend 0.046), and 3.03 versus 2.27 for trans FA (p trend 0.06). Among individual FA, the associations were significant for 18:2ω6, 18:3ω6, and trans 18:1 and marginally significant for 20:3ω6 and trans 18:2. The risk of becoming overweight or obese (defined as BMI ≥25 kg/m(2) at any follow-up time point) increased across increasing ω6/ω3 ratio (multivariable model p trend 0.04). In this prospective study, we found suggestive evidence that erythrocyte cis ω6 FA may be positively associated, and cis ω3 FA inversely associated with weight gain in initially normal-weight women.
    European Journal of Nutrition 03/2015; DOI:10.1007/s00394-015-0889-y · 3.84 Impact Factor
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    ABSTRACT: Observational data on the association between circulating 25(OH)D and colorectal cancer risk are limited in women. To determine whether prediagnostic levels of 25(OH)D were associated with risk of incident colorectal cancer in the Women's Health Study (WHS), we conducted a nested case-control study using 274 colorectal cases and 274 controls. Each case was matched to a control by age, ethnicity, fasting status at the time of blood collection, time of day when blood was drawn, and month of blood draw. Conditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for colorectal cancer by 25(OH)D quartiles. Mean plasma 25(OH)D was lower in cases versus controls (21.9 vs 23.9 ng/mL, p=0.01). In multivariable-adjusted logistic regression models, plasma 25(OH)D was significantly and inversely associated with odds of colorectal cancer (quartile 4 [Q4] versus quartile 1 [Q1]: OR (95% CI): 0.45 (0.25-0.81), ptrend 0.02). Additionally, we observed a somewhat lower risk of colorectal cancer mortality after adjustment for matching variables, randomization treatment and other risk factors (Q4:Q1 OR[95%CI]: 0.40(0.17-0.97); ptrend 0.05). In this cohort of healthy women, we found a significant inverse association between prediagnostic 25(OH)D levels and risk of incident colorectal cancer, and a borderline significant inverse association between prediagnostic 25(OH)D levels and colorectal cancer mortality. These results support a possible association between plasma 25(OH)D and risk of colorectal cancer in women. Received December 29, 2014. Revision received March 17, 2015. Accepted March 23, 2015.
    Cancer Prevention Research 03/2015; DOI:10.1158/1940-6207.CAPR-14-0470 · 5.27 Impact Factor
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    ABSTRACT: We hypothesized that higher concentrations of LDL particles (LDL-P) and leptin, and lower concentrations of HDL particles (HDL-P), and total and high molecular weight (HMW) adiponectin, would predict incident coronary heart disease (CHD) among severely obese postmenopausal women. In a case-cohort study nested in the Women's Health Initiative Observational Study, we sampled 677 of the 1852 white or black women with body mass index (BMI) ≥40 kg/m(2) and no prevalent cardiovascular disease (CVD), including all 124 cases of incident CHD over mean 5.0 year follow-up. Biomarkers were assayed on stored blood samples. In multivariable-adjusted weighted Cox models, higher baseline levels of total and small LDL-P, and lower levels of total and medium HDL-P, and smaller mean HDL-P size were significantly associated with incident CHD. In contrast, large HDL-P levels were inversely associated with CHD only for women without diabetes, and higher total and HMW adiponectin levels and lower leptin levels were associated with CHD only for women with diabetes. Higher total LDL-P and lower HDL-P were associated with CHD risk independently of confounders including CV risk factors and other lipoprotein measures, with adjusted HR (95%CIs) of 1.55(1.28, 1.88) and (0.70 (0.57, 0.85), respectively, and similar results for medium HDL-P. Higher CHD risk among severely obese postmenopausal women is strongly associated with modifiable concentrations of LDL-P and HDL-P, independent of diabetes, smoking, hypertension, physical activity, BMI and waist circumference. Severely obese postmenopausal women should be considered high risk candidates for lipid lowering therapy.
    03/2015; 120. DOI:10.1016/j.bbacli.2015.03.005

Publication Stats

74k Citations
9,821.71 Total Impact Points

Institutions

  • 1994–2015
    • Harvard University
      • Department of Nutrition
      Cambridge, Massachusetts, United States
  • 1991–2015
    • Brigham and Women's Hospital
      • • Division of Preventive Medicine
      • • Department of Medicine
      Boston, Massachusetts, United States
  • 1990–2015
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2014
    • University of Minnesota Duluth
      Duluth, Minnesota, United States
  • 2013
    • University of Washington Seattle
      • Department of Medicine
      Seattle, Washington, United States
    • University of Alabama at Birmingham
      • Department of Epidemiology
      Birmingham, AL, United States
    • The Ohio State University
      Columbus, Ohio, United States
    • McGill University
      • Department of Oncology
      Montréal, Quebec, Canada
    • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
      Torrance, California, United States
  • 2005–2013
    • University of Massachusetts Amherst
      • • Division of Biostatistics and Epidemiology
      • • Department of Public Health
      Amherst Center, Massachusetts, United States
    • German Institute of Human Nutrition
      • Department of Epidemiology
      Potsdam, Brandenburg, Germany
    • University of Pittsburgh
      • Division of General Internal Medicine
      Pittsburgh, PA, United States
  • 2012
    • Yale-New Haven Hospital
      New Haven, Connecticut, United States
  • 2011
    • HealthPartners Institute for Education and Research
      Bloomington, Minnesota, United States
    • University of California, San Francisco
      • Department of Obstetrics, Gynecology and Reproductive Sciences
      San Francisco, CA, United States
  • 2008–2011
    • Albert Einstein College of Medicine
      • Department of Epidemiology & Population Health
      New York City, New York, United States
    • University of East Anglia
      • Norwich Medical School
      Norwich, England, United Kingdom
    • Northwestern University
      • Feinberg School of Medicine
      Evanston, IL, United States
  • 2010
    • Medical University of South Carolina
      • Department of Medicine
      Charleston, South Carolina, United States
    • Kaiser Permanente
      Oakland, California, United States
  • 2009
    • John Wayne Cancer Institute
      Santa Monica, California, United States
  • 2005–2009
    • Partners HealthCare
      Boston, Massachusetts, United States
  • 2004–2009
    • Fred Hutchinson Cancer Research Center
      • Division of Public Health Sciences
      Seattle, WA, United States
    • Wake Forest School of Medicine
      • Division of Public Health Sciences
      Winston-Salem, North Carolina, United States
  • 2000–2009
    • Massachusetts Department of Public Health
      Boston, Massachusetts, United States
    • University of Alaska Anchorage
      Anchorage, Alaska, United States
  • 2005–2008
    • Beth Israel Deaconess Medical Center
      • Division of Endocrinology, Diabetes and Metabolism
      Boston, Massachusetts, United States
  • 2007
    • University of California, Los Angeles
      • Department of Epidemiology
      Los Angeles, CA, United States
  • 2006–2007
    • George Washington University
      • Department of Medicine
      Washington, Washington, D.C., United States
    • Tufts Medical Center
      • Division of Endocrinology, Diabetes and Metabolism
      Boston, Massachusetts, United States
    • University at Buffalo, The State University of New York
      • Department of Social and Preventive Medicine
      Buffalo, NY, United States
  • 2005–2007
    • Florida Atlantic University
      • Department of Biomedical Science
      Boca Raton, Florida, United States
  • 2004–2006
    • Massachusetts General Hospital
      • Department of Medicine
      Boston, Massachusetts, United States
    • Columbia University
      New York, New York, United States
  • 2004–2005
    • University of California, San Diego
      • Department of Family and Preventive Medicine
      San Diego, CA, United States
    • Simmons College
      • Program in Nutrition and Dietetics
      Boston, Massachusetts, United States
  • 2003
    • University of Iowa
      Iowa City, Iowa, United States
    • Vancouver General Hospital
      Vancouver, British Columbia, Canada
    • Boston Children's Hospital
      Boston, Massachusetts, United States
  • 2002
    • University of Zurich
      • Internal Medicine Unit
      Zürich, ZH, Switzerland
    • Boston University
      Boston, Massachusetts, United States
    • Dana-Farber Cancer Institute
      • Department of Medical Oncology
      Boston, MA, United States
  • 1996
    • William Penn University
      Filadelfia, Pennsylvania, United States