Walter C Willett

Brigham and Women's Hospital , Boston, Massachusetts, United States

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Publications (216)2073.02 Total impact

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    ABSTRACT: Background: Alcohol consumption is a consistent risk factor for breast cancer, and evidence suggests premenopausal plasma hormones are associated with breast cancer. Methods: Plasma concentrations of estradiol, estrone, estrone sulfate, testosterone, androstenedione, progesterone, prolactin, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), and sex hormone-binding globulin (SHBG) were measured in samples collected in 1996-99. Average alcohol intake was calculated from semi-quantitative food frequency questionnaires collected in 1995 and 1999. We used generalized linear models to calculate geometric mean hormone concentrations across alcohol categories and the percent difference for the highest vs. lowest category. Results: Comparing women who consumed >20 g/day with non-drinkers, levels were 25.7% higher for luteal estrone (geometric mean 106 vs. 84.5 pg/mL, trend test p-value=0.001), 27.2% higher for luteal estradiol (182 vs. 143 pg/mL, trend test p-value=0.006), and 16.8% higher for SHBG (85.6 vs. 73.3 nmol/L, trend test p-value =0.03); concentrations of free testosterone were 17.9% lower (0.16 vs. 0.20 ng/dL, trend test p-value=0.002). Women consuming >10g/day compared to non-drinkers had 26.5% higher concentrations of follicular estrone sulfate (950 vs. 751 pg/mL, trend test p-value=0.04). We did not observe significant associations between alcohol and the other sex hormones evaluated. Significant positive associations were observed with beer intake, but not other alcohol types, for DHEA (p-interaction=0.003) and androstenedione (p-interaction=0.006). Conclusion: Alcohol consumption was significantly positively associated with plasma luteal estrogen concentrations, but not with androgen levels, nor estrone or estradiol measured in the follicular phase. Impact: Differences in premenopausal estrogen levels may contribute to the association between alcohol and breast cancer.
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    ABSTRACT: Youth spend more time with screens than any activity except sleeping. Screen time is a risk factor for obesity, possibly because of the influence of food and beverage advertising on diet.
    American Journal of Clinical Nutrition 10/2014; 100(4):1173-81. · 6.50 Impact Factor
  • Walter C Willett, Meir J Stampfer, Frank M Sacks
    Annals of internal medicine 09/2014; 161(6):453. · 13.98 Impact Factor
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    ABSTRACT: The breast is particularly vulnerable to carcinogenic influences during adolescence due to rapid proliferation of mammary cells and lack of terminal differentiation. We investigated consumption of adolescent red meat and other protein sources in relation to breast cancer risk in the Nurses' Health Study II cohort.We followed prospectively 44,231 women aged 33-52 years who, in 1998, completed a detailed questionnaire about diet during adolescence. Relative risks (RR) and 95% confidence intervals (95%CI) were estimated using Cox proportional hazard regression.We documented 1132 breast cancer cases during 13-year follow-up. In multivariable Cox regression models with major breast cancer risk factors adjustment, greater consumption of adolescent total red meat was significantly associated with higher premenopausal breast cancer risk (highest vs lowest quintiles, RR, 1.42; 95%CI, 1.05-1.94; Ptrend=0.007), but not postmenopausal breast cancer. Adolescent poultry intake was associated with lower risk of breast cancer overall (RR, 0.75; 95%CI, 0.59-0.96; for each serving/day). Adolescent intakes of iron, heme iron, fish, eggs, legumes and nuts were not associated with breast cancer. Replacement of one serving/day of total red meat with one serving of combination of poultry, fish, legumes, and nuts was associated with a 16% lower risk of breast cancer overall (RR, 0.84; 95%CI, 0.74-0.96) and a 24% lower risk of premenopausal breast cancer (RR, 0.76; 95%CI, 0.64-0.92).Higher consumption of red meat during adolescence was associated with premenopausal breast cancer. Substituting other dietary protein sources for red meat in adolescent diet may decrease premenopausal breast cancer risk. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 09/2014; · 6.20 Impact Factor
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    ABSTRACT: Many changes in the economy, policies related to nutrition, and food processing have occurred within the United States since 2000, and the net effect on dietary quality is not clear. These changes may have affected various socioeconomic groups differentially.
    JAMA Internal Medicine 09/2014; · 13.25 Impact Factor
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    ABSTRACT: -Prior studies on intake of linoleic acid (LA), the predominant n-6 fatty acid, and coronary heart disease (CHD) risk have generated inconsistent results. We performed a systematic review and meta-analysis of prospective cohort studies to summarize the evidence regarding the relation of dietary LA intake and CHD risk.
    Circulation 08/2014; · 15.20 Impact Factor
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    ABSTRACT: Erythrocyte antioxidant enzymes are major circulating antioxidant enzymes in the oxidative stress defense system. Few prospective studies have assessed the association between these enzymes and the risk of coronary heart disease (CHD) in generally healthy adults. We conducted a prospective nested case-control study of CHD among 32,826 women at baseline with 15 years of follow-up from 1989 to 2004 in the Nurses' Health Study. We investigated the association of baseline erythrocyte superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities with the risk of CHD. A total of 365 cases and 728 controls were included in the analysis. Overall, the relative risks of CHD associated with 1-standard deviation higher SOD, GPx, and CAT activities were 1.07 (95% confidence interval (CI): 0.94, 1.22), 1.04 (95% CI: 0.91, 1.18), and 1.04 (95% CI: 0.92, 1.17), respectively. Multivariable adjustments did not change the associations appreciably. Fasting status did not modify the associations, with the exception that SOD activity was positively associated with the risk of CHD among participants who provided blood samples within 12 hours of fasting. Overall, activities of SOD, GPx, and CAT were not associated with CHD among women who were generally healthy at the time of blood collection.
    American journal of epidemiology. 08/2014;
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    ABSTRACT: Endogenous hormones are risk factors for postmenopausal breast cancer, and their measurement may improve our ability to identify high-risk women. Therefore, we evaluated whether inclusion of plasma estradiol, estrone, estrone sulfate, testosterone, dehydroepiandrosterone sulfate, prolactin, and sex hormone-binding globulin (SHBG) improved risk prediction for postmenopausal invasive breast cancer (n = 437 patient cases and n = 775 controls not using postmenopausal hormones) in the Nurses' Health Study.
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 08/2014;
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    ABSTRACT: Lower plasma magnesium levels may be associated with higher blood pressure and endothelial dysfunction, but sparse prospective data are available for stroke.
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    ABSTRACT: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent urologic disorder among men, but its etiology is still poorly understood. Our objective was to examine the relationship between physical activity and incidence of CP/CPPS in a large cohort of male health professionals.
    Medicine and science in sports and exercise. 08/2014;
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    ABSTRACT: The frequency of soda consumption remains high in the United States. Soda consumption has been associated with poor bone health in children, but few studies have examined this relation in adults, and to our knowledge, no study has examined the relation of soda consumption with risk of hip fractures.
    American Journal of Clinical Nutrition 08/2014; · 6.50 Impact Factor
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    ABSTRACT: We evaluated the associations of both maternal and paternal smoking during pregnancy with the risk of type 2 diabetes in daughters and explored whether any association was explained by weight at birth or BMI throughout life.
    Diabetes care. 08/2014;
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    ABSTRACT: In previous investigations of adolescent activity recalled in adulthood, modest reductions in risk of benign breast disease (BBD) and premenopausal breast cancer were seen with moderate-strenuous activity during high school. We therefore investigated physical activity, walking, and recreational inactivity (watching TV-videos, playing computer-videogames) reported by adolescent girls in relation to their subsequent risk for BBD as young women. The Growing Up Today Study includes 9,039 females, 9-15 years at study initiation (1996), who completed questionnaires annually through 2001, then in 2003, 2005, 2007, 2010 and 2013. Annual surveys (1996-2001) obtained data on physical and sedentary activities during the past year. Beginning in 2005, women (≥18 years) reported whether they had ever been diagnosed with BBD confirmed by breast biopsy (n = 133 cases, to 11/01/2013). Logistic regression (adjusted for baseline adiposity and age; additional factors in multivariable-adjusted models) estimated associations between adolescent activities (moderate-vigorous, walking, METS, inactivity) and biopsy-confirmed BBD in young women. Girls who walked the most had significantly lower risk of BBD (multivariable-adjusted OR = 0.61, ≥30 vs ≤15 min/day; p = .049). We observed no evidence that inactivity (≥3 vs <2 h/day OR = 1.02, p = .92) or METS (top vs bottom tertile OR = 1.19, p = .42) were associated with BBD. Accounting for factors including family history, childhood adiposity, and other activities and inactivities, adolescent girls who walked the most were at lower risk for BBD. We found no evidence that high moderate-vigorous activity might reduce risk, nor did we observe any association with inactivity. Continued follow-up will re-evaluate these findings as more BBD cases, and ultimately breast cancer, are diagnosed.
    Breast Cancer Research and Treatment 07/2014; · 4.47 Impact Factor
  • Diane Feskanich, Walter C Willett
    JAMA Pediatrics 07/2014; 168(7):683-684. · 4.28 Impact Factor
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    ABSTRACT: Little is known about the distinct perceptions towards rice and beans that may shape the consumption of these main staple foods among Costa Ricans. We aimed to identify barriers and motivators that could change the current staple into a healthier one, and assess the sensory perceptions of these foods in this population. Focus group discussions and sensory tastings of 8 traditional white or brown rice and beans preparations were conducted in 98 Costa Ricans, aged 40-65 y. Traditional habits and family support emerged as the two main drivers for current consumption. Consuming similar amounts of rice and beans, as well as unfamiliarity with brown rice, are habits engrained in the Costa Rican culture, and are reinforced in the family and community environment. Suggested strategies for consuming more brown rice and more beans included introducing them during childhood, disseminating information of their health benefits that take into account the importance of tradition, lowering the cost, increasing availability, engaging women as agents of change and for brown rice masking the perceived unpleasant sensory characteristics by incorporating them into mixed dishes. Plain brown rice received the lowest mean hedonic liking scores. The preparations rated highest for pleasant were the beans: rice 1:1 ratio regardless of the type of rice. This study identified novel strategies to motivate Costa Rican adults to adapt their food choices into healthier ones within their cultural and sensory acceptability.
    Appetite 06/2014; · 2.54 Impact Factor
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    ABSTRACT: Studies have shown that body weight is a determinant of health-related quality of life (HRQoL). However, few studies have examined long-term weight change with changes in HRQoL. We followed 52,682 women aged 46-71 years in the Nurses' Health Study (in 1992-2000) and 52,587 women aged 29-46 years in the Nurses' Health Study II (in 1993-2001). Body weight was self-reported, HRQoL was measured by the Medical Outcomes Study's 36-Item Short Form Health Survey, and both were updated every 4 years. The relationship between changes in weight and HRQoL scores was evaluated at 4-year intervals by using a generalized linear regression model with multivariate adjustment for baseline age, ethnicity, menopausal status, and changes in comorbidities and lifestyle factors. Weight gain of 15 lbs (1 lb = 0.45 kg) or more over a 4-year period was associated with 2.05-point lower (95% confidence interval: 2.14, 1.95) physical component scores, whereas weight loss of 15 lbs or more was associated with 0.89-point higher (95% confidence interval: 0.75, 1.03) physical component scores. Inverse associations were also found between weight change and physical function, role limitations due to physical problems, bodily pain, general health, and vitality. However, the relations of weight change with mental component scores, social functioning, mental health, and role limitations due to emotional problems were small.
    American journal of epidemiology. 06/2014;
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    ABSTRACT: Human studies suggest that oxidative stress is a risk factor for osteoporosis, but its relationship with fracture risk is poorly understood. The purpose of the present study was to investigate the association between biomarkers of oxidative stress and hip fracture in postmenopausal women. We conducted a prospective study in the Nurses' Health Study among 996 women aged 60 years or older at baseline blood collection in 1989-1990. Plasma fluorescent oxidation products (FlOPs) were measured at three excitation/emission wavelengths (360/420 nm named as FlOP_360; 320/420 nm named as FlOP_320 and 400/475 nm named as FlOP_400). FlOPs are generated from many different pathways (lipid, protein and DNA) and reflect a global oxidation burden. FlOP assay is 10-100 times more sensitive than measurement of malondialdehyde. We used Cox proportional hazards regression model to investigate the association between baseline plasma FlOPs and risk of hip fracture, adjusting for multiple hip fracture risk factors such as age, history of osteoporosis, history of hypertension, prior fracture and smoking status. Forty four hip fractures (4.4%) were identified during the follow-up (Maximum = 23 years). In the multivariable model, the hazard ratios (HR) of hip fracture in the second and third tertiles of FlOP_320 were 2.11 (95% confidence interval [CI] = 0.88-5.10) and 2.67 (95% CI = 1.14-6.27), respectively, in comparison with the lowest tertile, and the risk increased linearly with increasing FlOP_320 (P for trend = 0.021). Neither FlOP_360 nor FlOP_400 was significantly associated with risk of hip fracture (Tertile 3 versus tertile 1: HR = 0.70, 95% CI = 0.32-1.54, P for trend = 0.386 for FlOP_360; and HR = 0.88, 95% CI = 0.40-1.96, P for trend = 0.900 for FlOP_400). In this prospective study, higher plasma FlOP_320 was an independent risk factor for hip fracture. Our results need further confirmation. © 2014 American Society for Bone and Mineral Research.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 06/2014; · 6.04 Impact Factor
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    ABSTRACT: Through the processes of oxidation, polymerization, and hydrogenation, the cooking method of frying modifies both foods and their frying medium. However, it remains unknown whether the frequent consumption of fried foods is related to long-term cardiometabolic health.OBJECTIVE: We examined fried-food consumption and risk of developing incident type 2 diabetes (T2D) or coronary artery disease (CAD).DESIGN: Fried-food consumption was assessed by using a questionnaire in 70,842 women from the Nurses' Health Study (1984-2010) and 40,789 men from the Health Professionals Follow-Up Study (1986-2010) who were free of diabetes, cardiovascular disease, and cancer at baseline. Time-dependent Cox proportional hazards models were used to estimate RRs and 95% CIs for T2D and CAD adjusted for demographic, diet, lifestyle, and other cardiometabolic risk factors. Results were pooled by using an inverse variance-weighted random-effects meta-analysis.RESULTS: We documented 10,323 incident T2D cases and 5778 incident CAD cases. Multivariate-adjusted RRs (95% CIs) for individuals who consumed fried foods <1, 1-3, 4-6, or ≥7 times/wk were 1.00 (reference), 1.15 (0.97, 1.35), 1.39 (1.30, 1.49), and 1.55 (1.32, 1.83), respectively, for T2D and 1.00 (reference), 1.06 (0.98, 1.15), 1.23 (1.14, 1.33), and 1.21 (1.06, 1.39), respectively, for CAD. Associations were largely attenuated when we further controlled for biennially updated hypertension, hypercholesterolemia, and body mass index.CONCLUSIONS: Frequent fried-food consumption was significantly associated with risk of incident T2D and moderately with incident CAD, and these associations were largely mediated by body weight and comorbid hypertension and hypercholesterolemia.
    American Journal of Clinical Nutrition 06/2014; · 6.50 Impact Factor
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    ABSTRACT: Whether fat intake influences risk of developing more aggressive, lethal breast tumors is unknown. We evaluated intakes of total fat, specific types of fat, and cholesterol prior to diagnosis in relation to lethal breast cancer risk in 88,759 women in the Nurses’ Health Study (NHS; 1980–2010) and 93,912 women in the Nurses’ Health Study II (NHSII; 1991–2010). Diet was assessed every 4 years using a semi-quantitative food frequency questionnaire. Breast cancers were confirmed with pathology reports; deaths were confirmed by next of kin or the National Death Index. We defined lethal cases as women with invasive breast cancer who died of breast cancer. We pooled the cohorts and used multivariable Cox proportional hazards models. We identified 1,529 lethal breast cancer cases (1,279 in NHS and 250 in NHSII). Higher total fat intake was associated with a slightly lower lethal breast cancer risk (top vs. bottom quintile hazard ratio [HR] 0.85; 95 % CI 0.72, 1.01; p trend = 0.05). Specific types of fat were generally not associated with lethal breast cancer risk. For example, compared with those in the lowest quintile of saturated fat intake, those in the highest quintile had a HR of 0.98 (95 % CI 0.75, 1.26; p trend = 0.96). Among women diagnosed with breast cancer, pre-diagnosis fat intake was not associated with survival. Higher pre-diagnosis fat intake was not associated with greater risk of lethal breast cancer in these large prospective cohort studies, consistent with the weight of the evidence against a causal role for fat intake and breast cancer incidence.
    Breast Cancer Research and Treatment 06/2014; · 4.47 Impact Factor
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    ABSTRACT: Data from the WHO shows that the prevalence of overweight and obesity increased by ~20% between 2002 and 2010 in Nigeria. We conducted this study to examine the correlates of this fast growing epidemic.
    BMC Public Health 05/2014; 14(1):455. · 2.08 Impact Factor

Publication Stats

6k Citations
2,073.02 Total Impact Points


  • 1998–2014
    • Brigham and Women's Hospital
      • Department of Medicine
      Boston, Massachusetts, United States
  • 1986–2014
    • Harvard Medical School
      • • Division of Nutrition
      • • Department of Medicine
      Boston, Massachusetts, United States
  • 2006–2013
    • University of California, San Francisco
      • • Division of Hospital Medicine
      • • Division of General Internal Medicine
      San Francisco, California, United States
    • University of North Carolina at Chapel Hill
      • Carolina Population Center
      Chapel Hill, NC, United States
    • Albert Einstein College of Medicine
      • Department of Epidemiology & Population Health
      New York City, NY, United States
  • 1996–2013
    • Harvard University
      • • Department of Nutrition
      • • Department of Epidemiology
      Cambridge, Massachusetts, United States
  • 2011
    • Simmons College
      Boston, Massachusetts, United States
    • National Centre of Public Health Protection
      Ulpia Serdica, Sofia-Capital, Bulgaria
    • University of Copenhagen
      • Department of Human Nutrition
      Copenhagen, Capital Region, Denmark
  • 2010
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2009
    • Stanford University
      • Department of Dermatology
      Palo Alto, California, United States
    • University of Zurich
      Zürich, Zurich, Switzerland
  • 2006–2009
    • Massachusetts Department of Public Health
      Boston, Massachusetts, United States
  • 2008
    • KU Leuven
      • Laboratory for Experimental Medicine and Endocrinology (LEGENDO)
      Leuven, VLG, Belgium
    • Roswell Park Cancer Institute
      • Department of Health Behavior
      Buffalo, NY, United States
    • Maria Sklodowska Curie Memorial Cancer Centre
      Gleiwitz, Silesian Voivodeship, Poland
    • Uppsala University
      • Department of Public Health and Caring Sciences
      Uppsala, Uppsala, Sweden
  • 2007
    • VU University Amsterdam
      • IHS-Institute of Health Sciences
      Amsterdam, North Holland, Netherlands
  • 1995
    • Dana-Farber Cancer Institute
      • Department of Pediatric Oncology
      Boston, MA, United States