Walter C Willett

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

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Publications (228)2171.48 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Several dietary indices have been developed to measure overall diet quality, including the Healthy Eating Index-2005 (HEI-2005), which measures adherence to the 2005 Dietary Guidelines from the USDA; the Alternative Healthy Eating Index-2010 (AHEI-2010), which is based on foods and nutrients predictive of chronic disease risk; and the Alternate Mediterranean Diet Score (aMDS), which is an index that characterizes traditional food patterns of Mediterranean countries. Few studies have evaluated diet quality and ovarian cancer risk.Methods We assessed the associations of the HEI-2005, AHEI-2010, and aMDS with risk of epithelial ovarian cancer prospectively among women in the Nurses¿ Health Study. We used Cox proportional hazards models, adjusting for known ovarian cancer risk factors.ResultsDuring 24 years of follow-up, we documented 696 incident epithelial ovarian cancer cases among 82,948 women with diet information. The multivariate adjusted hazard ratios (95% confidence interval; Ptrend) of epithelial ovarian cancer comparing the highest with the lowest quintile were 1.03 (0.80-1.34; 0.77) for the AHEI-2010, 0.85 (0.65-1.12; 0.57) for the HEI-2005, and 0.91 (0.71-1.18; 0.44) for the aMDS.Conclusions We did not observe any clear association of three diet quality scores with ovarian cancer risk. Further work should other metrics of evaluating diet quality that may be more relevant cancer risk.
    Journal of Ovarian Research 12/2014; 7(1):112. · 2.43 Impact Factor
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    ABSTRACT: The vast amount of epidemiological evidence from three large US cohorts (Nurses’ Health Study, Nurses’ Health Study 2, and Health Professionals’ Follow-Up Study) has yielded important information regarding the roles of overall diet, individual foods and nutrients, physical activity, and other lifestyle factors in the development of type 2 diabetes. Excess adiposity is a major risk factor for diabetes, and thus maintaining a healthy body weight and avoidance of excess weight gain during adulthood is the cornerstone of diabetes prevention. Independent of body weight, the quality or type of dietary fat and carbohydrates is more crucial than the quantity in determining diabetes risk. Higher consumption of coffee, whole grains, fruits, and nuts is associated with lower risk of diabetes, whereas regular consumption of refined grains, red and processed meats, and sugar-sweetened beverages including fruits juices is associated with increased risk. Dietary patterns rich in fruits and vegetables, whole grains, and nuts and legumes, but lower in red and processed meats, refined grains, and sugar-sweetened beverages are consistently associated with reduced diabetes risk, even after adjustment for body mass index. The genome-wide association studies conducted in these cohorts have contributed substantially to the discoveries of novel genetic loci for type 2 diabetes and other metabolic traits, although the identified common variants explain only a small proportion of overall diabetes predisposition. Taken together, these ongoing large cohort studies have provided convincing epidemiologic evidence that a healthy diet, together with regular physical activity, maintenance of a healthy weight, moderate alcohol consumption, and avoidance of prolonged sedentary behaviors and smoking would prevent the majority of type 2 diabetes cases.
    Current Nutrition Reports. 12/2014; 3(4).
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    ABSTRACT: Previous observational studies of self-reported dairy product consumption and stroke risk have reported mixed findings. Few studies have used circulating biomarkers that provide objective measures of dairy fat intake. We tested the hypothesis that the circulating biomarkers of dairy fat, pentadecanoic acid (15:0), heptadecanoic acid (17:0), and trans palmitoleate (trans 16:1n-7), were associated with lower incidence of stroke, especially ischemic stroke. Secondarily, we evaluated 14:0, which is obtained from dairy products and beef, and also endogenously synthesized. In participants from 2 large US cohorts (the Health Professionals Follow-Up Study: 51,529 men; the Nurses' Health Study: 121,700 women) with stored blood samples in 1993-1994 (n = 18,225) and 1989-1990 (n = 32,826), respectively, we prospectively identified 594 incident stroke cases (median follow-up: 8.3 y) and matched them 1:1 to risk-set-sampled control subjects by age, sex, race, and smoking. Total plasma and red blood cell (RBC) fatty acids were measured by using gas-liquid chromatography. Covariates were assessed by using validated questionnaires. Stroke events and subtypes were adjudicated by using medical records or other supporting documentation. We used conditional logistic regression to estimate associations of fatty acids with incident stroke, and cohort-specific findings were combined by inverse-variance weights. After adjustment for demographic characteristics, lifestyle, cardiovascular disease risk factors, diet, and other circulating fatty acids, no significant associations with total stroke were seen for plasma 15:0 (pooled HR for highest compared with lowest quartiles: 0.85; 95% CI: 0.54, 1.33), 17:0 (0.99; 0.67, 1.49), trans 16:1 n-7 (0.89; 0.55, 1.45), or 14:0 (1.05; 0.62, 1.78). Results were similar for ischemic and hemorrhagic stroke subtypes, for RBC fatty acids, and in several different sensitivity analyses. In 2 large prospective cohorts, circulating biomarkers of dairy fat were not significantly associated with stroke. © 2014 American Society for Nutrition.
    American Journal of Clinical Nutrition 12/2014; 100(6):1437-47. · 6.50 Impact Factor
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    ABSTRACT: Background:Data from previous studies consistently suggest that maternal smoking is positively associated with the risk of obesity later in life. Whether this association persists across generations is unknown. Methods:We investigated the association between grandparent smoking status and grandchild overweight status among 3101 grandmother-mother-child triads in the Nurses’ Health Study II (NHS II), the NHS Mothers’ Cohort Study, and the children of NHS II participants who are in the Growing up Today Study (GUTS). Grandmothers of children provided information on their and their partner’s smoking during pregnancy with the child’s mother. Information on child's weight and height at ages 12 and 17 was obtained by self-report from the GUTS questionnaires. We used logistic regression to estimate odds ratios (ORs) of being overweight or obese, relative to normal weight. Results: Seventy-five percent of grandmothers reportedly did not smoke during pregnancy, while 4% quit during pregnancy, 13% continued smoking up to 14 cigarettes/day, and 7% smoked 15+ cigarettes daily throughout pregnancy. Grand-maternal smoking was not associated with being overweight or obese at age 12 or 17 years, in boys or in girls. After adjusting for multiple covariates, the OR of being overweight or obese relative to normal weight at age 12 years in girls whose grandmothers smoked 15+ cigarettes per day during pregnancy with their mothers was 1.23 (95% CI 0.75-2.01; ptrend = 0.25) and 1.08 (0.65-1.97; ptrend = 0.34) in boys. Grand-paternal smoking was positively associated with being overweight or obese at age 12 years in girls but not boys, and not at age 17 years for either: the OR for being overweight or obese at age 12 years was 1.46 (95% CI 1.07-1.99; ptrend = 0.01) in girls, and 1.26 (95% CI 0.94-1.70; ptrend = 0.11) in boys. After restricting to children of non-smoking mothers, the comparable OR for granddaughter obesity was attenuated and no longer significant [OR 1.35 (95% CI 0.93-1.97; ptrend= 0.10)]. Conclusions: Our findings suggest that grand-maternal smoking is not associated with adolescent overweight status in the grandchild. However, grand-paternal smoking may affect overweight status of the granddaughter, likely through the association between grand-paternal smoking and maternal smoking.
    142nd APHA Annual Meeting and Exposition 2014; 11/2014
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    ABSTRACT: Dietary exposures during adolescence may exert important effects on breast development and future breast cancer risk. This study evaluated the associations between high school intakes of fat and micronutrients and the incidence of proliferative benign breast disease (BBD), a marker of increased breast cancer risk.
    Cancer causes & control : CCC. 11/2014;
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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.
    10/2014;
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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
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    ABSTRACT: While early-life body leanness is associated with increased breast cancer risk, early-life physical activity may protect against breast cancer. We examined whether the excess risk among lean girls is modified by their levels of prior, concurrent, or future physical activity. We conducted an analysis among 74,723 women in the Nurses' Health Study II (follow-up 1997-2011). Participants recalled their body size at ages 5, 10, and 20 years in 1989 using a 9-level pictogram (level 1: most lean). In 1997, they reported adolescent levels of physical activity (ages 12-13 and 14-17 years). Cox proportional hazards models estimated the overall association of body size with breast cancer risk and assessed interactions of adolescent physical activity with body size at three different age periods (5-10, 10-20, and 20 years), adjusting for early-life and adult risk factors for breast cancer. Regardless of levels of adolescent physical activity, early-life body leanness (level 1-2 vs. 4.5+) was significantly associated with higher breast cancer risk. The association was slightly attenuated among those who were active (60+ MET-hr/wk) during adolescence compared to those who were inactive (<30 MET-hr/wk) (body size at ages 5-10 years: hazard ratio=1.37, 95% confidence interval=1.04-1.81 vs. 1.66, 1.29-2.12), but the interaction was not significant (p=0.72). The results were similar for body size at three different age periods. Being lean during early life is a risk factor for breast cancer among both inactive and active girls. Adolescent physical activity did not significantly modify the association, although some interaction cannot be excluded. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 10/2014; · 6.20 Impact Factor
  • Bernard Rosner, Sara Hendrickson, Walter Willett
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    ABSTRACT: Nutrient intake is often measured with substantial error both in commonly used surrogate instruments such as a food frequency questionnaire (FFQ) and in gold standard-type instruments such as a diet record (DR). If there is a correlated error between the FFQ and DR, then standard measurement error correction methods based on regression calibration can produce biased estimates of the regression coefficient (λ) of true intake on surrogate intake. However, if a biomarker exists and the error in the biomarker is independent of the error in the FFQ and DR, then the method of triads can be used to obtain unbiased estimates of λ, provided that there are replicate biomarker data on at least a subsample of validation study subjects. Because biomarker measurements are expensive, for a fixed budget, one can use a either design where a large number of subjects have one biomarker measure and only a small subsample is replicated or a design that has a smaller number of subjects and has most or all subjects validated. The purpose of this paper is to optimize the proportion of subjects with replicated biomarker measures, where optimization is with respect to minimizing the variance of . The methodology is illustrated using vitamin C intake data from the European Prospective Investigation into Cancer and Nutrition study where plasma vitamin C is the biomarker. In this example, the optimal validation study design is to have 21% of subjects with replicated biomarker measures. Copyright © 2014 John Wiley & Sons, Ltd.
    Statistics in Medicine 10/2014; · 2.04 Impact Factor
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    ABSTRACT: Additive interactions can have public health and etiological implications but are infrequently reported. We assessed departures from additivity on the absolute risk scale between 9 established breast cancer risk factors and 23 susceptibility single-nucleotide polymorphisms (SNPs) identified from genome-wide association studies among 10,146 non-Hispanic white breast cancer cases and 12,760 controls within the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium. We estimated the relative excess risk due to interaction and its 95% confidence interval for each pairwise combination of SNPs and nongenetic risk factors using age- and cohort-adjusted logistic regression models. After correction for multiple comparisons, we identified a statistically significant relative excess risk due to interaction (uncorrected P = 4.51 × 10(-5)) between a SNP in the DNA repair protein RAD51 homolog 2 gene (RAD51L1; rs10483813) and body mass index (weight (kg)/height (m)(2)). We also compared additive and multiplicative polygenic risk prediction models using per-allele odds ratio estimates from previous studies for breast-cancer susceptibility SNPs and observed that the multiplicative model had a substantially better goodness of fit than the additive model.
    American journal of epidemiology. 09/2014;
  • 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.
    08/2014;
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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;

Publication Stats

6k Citations
2,171.48 Total Impact Points

Institutions

  • 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