Walter C Willett

Harvard University, Cambridge, Massachusetts, United States

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Publications (346)3182.12 Total impact

  • [Show abstract] [Hide abstract] ABSTRACT: Purpose: The influence of reproductive factors on colorectal cancer, including oral contraceptive (OC) use, has been examined, but less research is available on OC use and adenomas. Methods: Participants of the Nurses' Health Study who had a lower bowel endoscopy between 1986 (when endoscopies were first assessed) and 2008 were included in this study. Multivariable logistic regression models for clustered data were used to estimate odds ratios and 95 % confidence intervals [OR (95 % CIs)]. Results: Among 73,058 participants, 51 % (n = 37,382) reported ever using OCs. Ever OC use was associated with a slight increase in non-advanced adenomas [OR 1.11, 95 % CI (1.02, 1.21)] but not with any other endpoints. Duration of OC use was not associated with adenomas, but longer times since last OC use were associated with increased odds of adenomas [e.g., compared to never use, 15+ years since last use: OR 1.17 (1.07, 1.27)]. Shorter times since last OC use were inversely associated [e.g., ≤4 years since last use: OR 0.74 (0.65, 0.84)]. Conclusions: We observed a modest borderline increase in risk of colorectal adenomas with any prior OC use. Additionally, more recent OC use may decrease risk, while exposure in the distant past may modestly increase risk of adenomas.
    No preview · Article · Apr 2016 · Cancer Causes and Control
  • [Show abstract] [Hide abstract] ABSTRACT: Background: Heterocyclic amines (HCAs) in cooked meats may play a role in colorectal cancer (CRC) development. Objectives: To prospectively examine the association between estimated intakes of HCAs and meat derived mutagenicity (MDM) in two cohorts of health professionals, the Health Professionals Follow-up Study (HPFS) and the Nurses' Health Study (NHS). Methods: In 29,615 men and 65,875 women, intake of the HCAs 2-amino-3,8-dimethylimidazo quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo pyridine (PhIP), 2-amino-3,4,8-trimethylimidazo (DiMeIQx) and MDM was estimated using a 1996 cooking questionnaire, the 1994 food frequency questionnaire and an online database. Cox Proportional Hazards models were used to estimate hazard ratios (HR), 95% confidence intervals (95% CI) and to adjust for potential confounders. Estimates for both cohorts were pooled using random-effects meta-analysis. Results: Between 1996 and 2010, 418 male and 790 female CRC cases were identified. Meat mutagen intake was not statistically significantly associated with risk of CRC [highest vs. lowest quintile, pooled HR (95% CI) for MeIQx: 1.12 (0.93, 1.34), P for trend 0.23; PhIP: 1.10 (0.90, 1.33), P for trend 0.35; MDM: 1.03 (0.86, 1.24), P for trend 0.75] or subtypes of CRC defined by tumor location (proximal, distal or rectum). When analyzed by source of meat, PhIP from red, but not from white meat, was non-significantly positively associated with CRC and significantly positively associated with proximal cancers [HR (95% CI) per standard deviation increase of log-transformed intake: PhIP red meat: CRC: 1.06 (0.99, 1.12), proximal: 1.11 (1.02, 1.21); PhIP white meat: CRC: 0.99 (0.94, 1.04), proximal: 1.00 (0.93, 1.09)]. Conclusions: Estimated intakes of meat mutagens were not significantly associated with CRC risk over 14 years of follow-up in the NHS and HPFS cohorts. Results for PhIP from red, but not from white meat warrant further investigation.
    No preview · Article · Apr 2016 · Environmental Health Perspectives
  • G. Fehringer · P. Kraft · P. D. P. Pharoah · R. A. Eeles · N. Chatterjee · F. R. Schumacher · J. M. Schildkraut · S. Lindstrom · P. Brennan · H. Bickebo ller · [...] · J. Gong · U. Peters · S. B. Gruber · C. I. Amos · T. A. Sellers · D. F. Easton · D. J. Hunter · C. A. Haiman · B. E. Henderson · R. J. Hung ·
    No preview · Article · Apr 2016 · Cancer Research
  • No preview · Article · Apr 2016 · Gastroenterology
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    [Show abstract] [Hide abstract] ABSTRACT: Background: -In prospective studies, relationship of self-reported consumption of dairy foods with risk of diabetes mellitus is inconsistent. Few studies have assessed dairy fat, using circulating biomarkers, and incident diabetes. We tested hypothesis that circulating fatty acid biomarkers of dairy fat, 15:0, 17:0, and t-16:1n-7, are associated with lower incident diabetes. Methods and results: -Among 3,333 adults aged 30-75 years and free of prevalent diabetes at baseline, total plasma and erythrocyte fatty acids were measured in blood collected in 1989-90 (Nurses' Health Study) and 1993-94 (Health Professionals Follow-Up Study). Incident diabetes through 2010 was confirmed by validated supplementary questionnaire based on symptoms, diagnostic tests, and medications. Risk was assessed using Cox proportional hazards, with cohort findings combined by meta-analysis. During mean±SD follow-up of 15.2±5.6 years, 277 new cases of diabetes were diagnosed. In pooled multivariate analyses adjusting for demographics, metabolic risk-factors, lifestyle, diet, and other circulating fatty acids, individuals with higher plasma 15:0 had 44% lower risk of diabetes (quartiles 4 vs. 1, HR=0.56, 95%CI=0.37-0.86; P-trend=0.01); higher plasma 17:0, 43% lower risk (HR=0.57, 95%CI=0.39-0.83, P-trend=0.01); and higher t-16:1n-7, 52% lower risk (HR=0.48, 95%CI=0.33-0.70, P-trend <0.001). Findings were similar for erythrocyte 15:0, 17:0, and t-16:1n-7, although with broader CIs that only achieved statistical significance for 17:0. Conclusions: -In two prospective cohorts, higher plasma dairy fatty acid concentrations were associated with lower incident diabetes. Results were similar for erythrocyte 17:0. Our findings highlight need to better understand potential health effects of dairy fat; and dietary and metabolic determinants of these fatty acids.
    Full-text · Article · Mar 2016 · Circulation
  • No preview · Article · Mar 2016 · Cancer Epidemiology Biomarkers & Prevention
  • [Show abstract] [Hide abstract] ABSTRACT: Importance The US Preventive Services Task Force recently recommended the use of aspirin to prevent colorectal cancer and cardiovascular disease among many US adults. However, the association of aspirin use with the risk for other cancer types and the potential population-wide effect of aspirin use on cancer, particularly within the context of screening, remain uncertain.Objectives To examine the potential benefits of aspirin use for overall and subtype-specific cancer prevention at a range of doses and durations of use and to estimate the absolute benefit of aspirin in the context of screening.Design, Setting, and Participants Two large US prospective cohort studies, the Nurses’ Health Study (1980-2010) and Health Professionals Follow-up Study (1986-2012), followed up 135 965 health care professionals (88 084 women and 47 881 men, respectively) who reported on aspirin use biennially. The women were aged 30 to 55 years at enrollment in 1976; the men, aged 40 to 75 years in 1986. Final follow-up was completed on June 30, 2012, for the Nurses’ Health Study cohort and January 31, 2010, for the Health Professionals Follow-up Study cohort, and data were accessed from September 15, 2014, to December 17, 2015.Main Outcomes and Measures Relative risks (RRs) for incident cancers and population-attributable risk (PAR).Results Among the 88 084 women and 47 881 men who underwent follow-up for as long as 32 years, 20 414 cancers among women and 7571 cancers among men were documented. Compared with nonregular use, regular aspirin use was associated with a lower risk for overall cancer (RR, 0.97; 95% CI, 0.94-0.99), which was primarily owing to a lower incidence of gastrointestinal tract cancers (RR, 0.85; 95% CI, 0.80-0.91), especially colorectal cancers (RR, 0.81; 95% CI, 0.75-0.88). The benefit of aspirin on gastrointestinal tract cancers appeared evident with the use of at least 0.5 to 1.5 standard aspirin tablets per week; the minimum duration of regular use associated with a lower risk was 6 years. Among individuals older than 50 years, regular aspirin use could prevent 33 colorectal cancers per 100 000 person-years (PAR, 17.0%) among those who had not undergone a lower endoscopy and 18 colorectal cancers per 100 000 person-years (PAR, 8.5%) among those who had. Regular aspirin use was not associated with the risk for breast, advanced prostate, or lung cancer.Conclusions and Relevance Long-term aspirin use was associated with a modest but significantly reduced risk for overall cancer, especially gastrointestinal tract tumors. Regular aspirin use may prevent a substantial proportion of colorectal cancers and complement the benefits of screening.
    No preview · Article · Mar 2016
  • Holly R. Harris · Walter C. Willett · Rita L. Vaidya · Karin B. Michels
    [Show abstract] [Hide abstract] ABSTRACT: Mammary tissue experiences the highest rate of proliferation during adolescence representing a period of heightened susceptibility. Few prospective studies have examined adolescent diet and breast cancer, and none have examined dietary patterns. Thus, we examined the association between adolescent dietary patterns and a diet quality index, the Alternative Healthy Eating Index(AHEI), and breast cancer in the Nurses’ Health Study II among those who completed a 124-item food frequency questionnaire about their high school diet(HS-FFQ). Cox proportional hazards regression models were used to calculate hazard ratios(HR) and 95% confidence intervals(95% CI). Among 45,204 women who completed the HS-FFQ, 863 cases of premenopausal breast cancer and 614 cases of postmenopausal cancer were diagnosed. A marginal inverse association was observed between the “prudent” dietary pattern, characterized by high intake of vegetables, fruits, legumes, fish, and poultry, and premenopausal breast cancer. Women in fifth quintile had a multivariable adjusted HR (95% CI) of 0.84 (0.67-1.04) for premenopausal breast cancer(ptrend=0.07) compared to the first quintile. Scoring higher on the AHEI was borderline significantly associated with premenopausal breast cancer with a HR of 0.81 (0.64-1.01) for the fifth quintile(ptrend=0.08) and this association appeared to be stronger for ER-negative/PR-negative tumors. No association was observed between the “Western” pattern or the “fast food” pattern. Results were similar for each of these patterns when both pre and postmenopausal breast cancer were considered together. An overall healthy diet during adolescence, similar to the prudent dietary pattern or adherence to the AHEI, may contribute to reducing the risk of breast cancer.
    No preview · Article · Feb 2016 · Carcinogenesis
  • [Show abstract] [Hide abstract] ABSTRACT: We examined associations between dietary quality indices and breast cancer risk by molecular subtype among 100,643 women in the prospective Nurses’ Health Study (NHS) cohort, followed from 1984 to 2006. Dietary quality scores for the Alternative Healthy Eating Index (AHEI), alternate Mediterranean diet (aMED), and Dietary Approaches to Stop Hypertension (DASH) dietary patterns were calculated from semi-quantitative food frequency questionnaires collected every 2–4 years. Breast cancer molecular subtypes were defined according to estrogen receptor (ER), progesterone receptor, human epidermal growth factor 2 (HER2), cytokeratin 5/6 (CK5/6), and epidermal growth factor receptor status from immunostained tumor microarrays in combination with histologic grade. Cox proportional hazards models, adjusted for age and breast cancer risk factors, were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs). Competing risk analyses were used to assess heterogeneity by subtype. We did not observe any significant associations between the AHEI or aMED dietary patterns and risk of breast cancer by molecular subtype. However, a significantly reduced risk of HER2-type breast cancer was observed among women in 5th versus 1st quintile of the DASH dietary pattern [n = 134 cases, Q5 vs. Q1 HR (95 % CI) = 0.44 (0.25–0.77)], and the inverse trend across quintiles was significant (p trend = 0.02). We did not observe any heterogeneity in associations between AHEI (p het = 0.25), aMED (p het = 0.71), and DASH (p het = 0.12) dietary patterns and breast cancer by subtype. Adherence to the AHEI, aMED, and DASH dietary patterns was not strongly associated with breast cancer molecular subtypes.
    No preview · Article · Feb 2016 · Breast Cancer Research and Treatment
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    [Show abstract] [Hide abstract] ABSTRACT: Background The prevailing efforts for cardiovascular disease (CVD) prevention focused on treatment of common CVD risk factors rather than primordial prevention of risk factors through health behaviors. The previously validated Healthy Heart Score effectively predicted the 20-year risk of CVD in midadulthood; however, it is unknown whether this risk score is associated with clinically relevant CVD risk factors. Methods and Results We analyzed the association between the Healthy Heart Score and the incidence of clinical CVD risk factors, including diabetes mellitus, hypertension, and hypercholesterolemia among 69 505 US women in the Nurses' Health Study II (NHSII; 1991-2011). The Healthy Heart Score estimates the 20-year CVD risk based on 9 lifestyle factors; thus, a higher score reflected a higher predictive CVD risk. During 20 years, we documented 3275 incident cases of diabetes mellitus, 17 420 of hypertension, and 24 385 of hypercholesterolemia. Women with higher predicted CVD risk based on the Healthy Heart Score (highest quintile versus lowest quintile) had significantly greater risk of each clinical risk factor individually (hazard ratios: 18.1 [95% confidence interval, 14.4-22.7] for diabetes mellitus, 5.10 [4.66-5.57] for hypertension, and 2.57 [2.40-2.75] for hypercholesterolemia). The hazard ratio for developing the high-CVD profile was 52.5 (33.6-82.1). These associations were most pronounced among women who were younger, were nonsmokers, or had optimal weight. Conclusions An absolute 20-year risk of CVD, estimated by the Healthy Heart Score, was strongly associated with the development of CVD clinically relevant risk factors. This risk score may serve as the first step for CVD risk assessment in primordial prevention.
    Full-text · Article · Feb 2016 · Circulation Cardiovascular Quality and Outcomes
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    Preview · Article · Jan 2016 · BMJ (online)
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    No preview · Dataset · Jan 2016
  • [Show abstract] [Hide abstract] ABSTRACT: Adolescence is hypothesized to be a time period of particular susceptibility to breast cancer risk factors. Red meat and fat intake during high school was positively associated with risk of breast cancer among premenopausal women in the Nurses’ Health Study II (NHSII). High mammographic density is a strong predictor of breast cancer risk but there is limited research on dietary factors associated with breast density. To test the hypothesis that high intake of animal fat or red meat during adolescence is associated with mammographic density, we analyzed data from premenopausal women in the NHSII. Participants recalled adolescent diet on a high school food frequency questionnaire. We assessed absolute and percent mammographic density on digitized analog film mammograms for 687 premenopausal women with no history of cancer. We used generalized linear regression to quantify associations of adolescent animal fat and red meat intake with mammographic density, adjusting for age, body mass index, and other predictors of mammographic density. Adolescent animal fat intake was significantly positively associated with premenopausal mammographic density, with a mean percent density of 39.2 % in the lowest quartile of adolescent animal fat intake versus 43.1 % in the highest quartile (p trend: 0.03). A non-significant positive association was also observed for adolescent red meat intake (p trend: 0.14). These findings suggest that higher adolescent animal fat intake is weakly associated with percent mammographic density in premenopausal women.
    No preview · Article · Jan 2016 · Breast Cancer Research and Treatment
  • [Show abstract] [Hide abstract] ABSTRACT: Importance Nitric oxide signaling alterations in outflow facility and retinal blood flow autoregulation are implicated in primary open-angle glaucoma (POAG). Nitric oxide donation has emerged as a POAG therapeutic target. An exogenous source of nitric oxide is dietary nitrates.Objective To evaluate the association between dietary nitrate intake, derived mainly from green leafy vegetables, and POAG.Design, Setting, and Participants We followed up participants biennially in the prospective cohorts of the Nurses’ Health Study (63 893 women; 1984-2012) and the Health Professionals Follow-up Study (41 094 men; 1986-2012) at each 2-year risk period. Eligible participants were 40 years or older, were free of POAG, and reported eye examinations.Exposures The primary exposure was dietary nitrate intake. Information on diet and potential confounders was updated with validated questionnaires.Main Outcomes and Measures The main outcome was the incidence of POAG and POAG subtypes; 1483 cases were confirmed with medical records and classified into subtypes defined by intraocular pressure (IOP) (≥22 or <22 mm Hg) or by visual field (VF) loss pattern at diagnosis (peripheral loss only or early paracentral loss). Cohort-specific and pooled multivariable rate ratios (MVRRs) and 95% CIs were estimated.Results During 1 678 713 person-years of follow-up, 1483 incident cases of POAG were identified. The mean (SD) age for the 1483 cases was 66.8 (8.3). Compared with the lowest quintile of dietary nitrate intake (quintile 1: approximately 80 mg/d), the pooled MVRR for the highest quintile (quintile 5: approximately 240 mg/d) was 0.79 (95% CI, 0.66-0.93; P for trend = .02). The dose response was stronger (P for heterogeneity = .01) for POAG with early paracentral VF loss (433 cases; quintile 5 vs quintile 1 MVRR = 0.56; 95% CI, 0.40-0.79; P for trend < .001) than for POAG with peripheral VF loss only (835 cases; quintile 5 vs quintile 1 MVRR = 0.85; 95% CI, 0.68-1.06; P for trend = .50). The association did not differ (P for heterogeneity = .75) by POAG subtypes defined by IOP (997 case patients with IOP ≥22 mm Hg: quintile 5 vs quintile 1 MVRR = 0.82; 95% CI, 0.67-1.01; P for trend = .11; 486 case patients with IOP <22 mm Hg: quintile 5 vs quintile 1 MVRR = 0.71; 95% CI, 0.53-0.96; P for trend = .12). Green leafy vegetables accounted for 56.7% of nitrate intake variation. Compared with consuming 0.31 servings per day, the MVRR for consuming 1.45 or more servings per day was 0.82 for all POAG (95% CI, 0.69-0.97; P for trend = .02) and 0.52 for POAG with paracentral VF loss (95% CI, 0.29-0.96; P for trend < .001).Conclusions and Relevance Higher dietary nitrate and green leafy vegetable intake was associated with a lower POAG risk, particularly POAG with early paracentral VF loss at diagnosis.
    No preview · Article · Jan 2016 · Jama Ophthalmology
  • [Show abstract] [Hide abstract] ABSTRACT: Background: Carbohydrate quality has been consistently related to the risk of type 2 diabetes (T2D). However, limited information is available about the effect of carbohydrate quality on biomarkers related to T2D. Objective: We examined the associations of carbohydrate quality measures (CQMs) including carbohydrate intake; starch intake; glycemic index; glycemic load; total, cereal, fruit, and vegetable fiber intakes; and different combinations of these nutrients with plasma concentrations of adiponectin, C-reactive protein (CRP), and glycated hemoglobin (HbA1c). Methods: This is a cross-sectional analysis of 2458 diabetes-free women, ages 43-70 y, in the Nurses Health Study. CQMs were estimated from food-frequency questionnaires, and averages from 1984, 1986, and 1990 were used. Plasma biomarkers were collected in 1990. Multiple linear regression models were used to assess the associations between CQMs and biomarkers. Results: After age, body mass index, lifestyle, and dietary variables were adjusted, 1) total fiber intake was positively associated with adiponectin (P-trend = 0.004); 2) cereal fiber intake was positively associated with adiponectin and inversely associated with CRP, and fruit fiber intake was negatively associated with HbA1c concentrations (all P-trend < 0.03); 3) starch intake was inversely associated with adiponectin (P-trend = 0.02); 4) a higher glycemic index was associated with lower adiponectin and higher HbA1c (both P-trend < 0.05); 5) a higher carbohydrate-to-total fiber intake ratio was associated with lower adiponectin (P-trend = 0.005); 6) a higher starch-to-total fiber intake ratio was associated with lower adiponectin and higher HbA1c (both P-trend < 0.05); and 7) a higher starch-to-cereal fiber intake ratio was associated with lower adiponectin (P-trend = 0.002). Conclusions: A greater fiber intake and a lower starch-to-fiber intake ratio are favorably associated with adiponectin and HbA1c, but only cereal fiber intake was associated with CRP in women. Further research is warranted to understand the potential mechanism of these associations in early progression of T2D.
    No preview · Article · Jan 2016 · Journal of Nutrition
  • [Show abstract] [Hide abstract] ABSTRACT: Importance Vitamin D deficiency has been associated with poor physical performance.Objective To determine the effectiveness of high-dose vitamin D in lowering the risk of functional decline.Design, Setting, and Participants One-year, double-blind, randomized clinical trial conducted in Zurich, Switzerland. The screening phase was December 1, 2009, to May 31, 2010, and the last study visit was in May 2011. The dates of our analysis were June 15, 2012, to October 10, 2015. Participants were 200 community-dwelling men and women 70 years and older with a prior fall.Interventions Three study groups with monthly treatments, including a low-dose control group receiving 24 000 IU of vitamin D3 (24 000 IU group), a group receiving 60 000 IU of vitamin D3 (60 000 IU group), and a group receiving 24 000 IU of vitamin D3 plus 300 μg of calcifediol (24 000 IU plus calcifediol group).Main Outcomes and Measures The primary end point was improving lower extremity function (on the Short Physical Performance Battery) and achieving 25-hydroxyvitamin D levels of at least 30 ng/mL at 6 and 12 months. A secondary end point was monthly reported falls. Analyses were adjusted for age, sex, and body mass index.Results The study cohort comprised 200 participants (men and women ≥70 years with a prior fall). Their mean age was 78 years, 67.0% (134 of 200) were female, and 58.0% (116 of 200) were vitamin D deficient (<20 ng/mL) at baseline. Intent-to-treat analyses showed that, while 60 000 IU and 24 000 IU plus calcifediol were more likely than 24 000 IU to result in 25-hydroxyvitamin D levels of at least 30 ng/mL (P = .001), they were not more effective in improving lower extremity function, which did not differ among the treatment groups (P = .26). However, over the 12-month follow-up, the incidence of falls differed significantly among the treatment groups, with higher incidences in the 60 000 IU group (66.9%; 95% CI, 54.4% to 77.5%) and the 24 000 IU plus calcifediol group (66.1%; 95% CI, 53.5%-76.8%) group compared with the 24 000 IU group (47.9%; 95% CI, 35.8%-60.3%) (P = .048). Consistent with the incidence of falls, the mean number of falls differed marginally by treatment group. The 60 000 IU group (mean, 1.47) and the 24 000 IU plus calcifediol group (mean, 1.24) had higher mean numbers of falls compared with the 24 000 IU group (mean, 0.94) (P = .09).Conclusions and Relevance Although higher monthly doses of vitamin D were effective in reaching a threshold of at least 30 ng/mL of 25-hydroxyvitamin D, they had no benefit on lower extremity function and were associated with increased risk of falls compared with 24 000 IU.Trial Registration Identifier: NCT01017354
    No preview · Article · Jan 2016 · JAMA Internal Medicine
  • Lea Borgi · Isao Muraki · Ambika Satija · Walter C Willett · Eric B Rimm · John P Forman
    [Show abstract] [Hide abstract] ABSTRACT: Increased fruit and vegetable intake lowers blood pressure in short-term interventional studies. However, data on the association of long-term intake of fruits and vegetables with hypertension risk are scarce. We prospectively examined the independent association of whole fruit (excluding juices) and vegetable intake, as well as the change in consumption of whole fruits and vegetables, with incident hypertension in 3 large longitudinal cohort studies: Nurses' Health Study (n=62 175), Nurses' Health Study II (n=88 475), and Health Professionals Follow-up Study (n=36 803). We calculated hazard ratios and 95% confidence intervals for fruit and vegetable consumption while controlling for hypertension risk factors. Compared with participants whose consumption was ≤4 servings/week, the pooled hazard ratios among those whose intake was ≥4 servings/day were 0.92(0.87-0.97) for total whole fruit intake and 0.95(0.86-1.04) for total vegetable intake. Similarly, compared with participants who did not increase their fruit or vegetable consumption, the pooled hazard ratios for those whose intake increased by ≥7 servings/week were 0.94(0.90-0.97) for total whole fruit intake and 0.98(0.94-1.01) for total vegetable. Analyses of individual fruits and vegetables yielded different results. Consumption levels of ≥4 servings/week (as opposed to <1 serving/month) of broccoli, carrots, tofu or soybeans, raisins, and apples was associated with lower hypertension risk. In conclusion, our results suggest that greater long-term intake and increased consumption of whole fruits may reduce the risk of developing hypertension.
    No preview · Article · Dec 2015 · Hypertension
  • [Show abstract] [Hide abstract] ABSTRACT: The influence of adiposity over life course on cancer risk remains poorly understood. We assessed trajectories of body shape from age 5 up to 60 using a group-based modeling approach among 73,581 women from the Nurses' Health Study and 32,632 men from the Health Professionals Follow-up Study. After a median of approximately 10 years of follow-up, we compared incidence of total and obesity-related cancers (cancers of the esophagus [adenocarcinoma only], colorectum, pancreas, breast [after menopause], endometrium, ovaries, prostate [advanced only], kidney, liver and gallbladder) between these trajectories. We identified 5 distinct trajectories of body shape: lean-stable, lean-moderate increase, lean-marked increase, medium-stable, and heavy-stable/increase. Compared with women in the lean-stable trajectory, those in the lean-marked increase and heavy-stable/increase trajectories had a higher cancer risk in the colorectum, esophagus, pancreas, kidney, and endometrium (relative risk [RR] ranged from 1.22 to 2.56). Early life adiposity was inversely while late life adiposity was positively associated with postmenopausal breast cancer risk. In men, increased body fatness at any life period was associated with a higher risk of esophageal adenocarcinoma and colorectal cancer (RR ranged from 1.23 to 3.01), and the heavy-stable/increase trajectory was associated with a higher risk of pancreatic cancer, but lower risk of advanced prostate cancer. The trajectory-cancer associations were generally stronger for non-smokers and women who did not use menopausal hormone therapy. In conclusion, trajectories of body shape throughout life were related to cancer risk with varied patterns by sex and organ, indicating a role for lifetime adiposity in carcinogenesis. This article is protected by copyright. All rights reserved.
    No preview · Article · Dec 2015 · International Journal of Cancer
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    [Show abstract] [Hide abstract] ABSTRACT: Benign breast disease (BBD) is a well-established risk factor for breast cancer, but little work has considered a girl's early life and her risk for BBD in adulthood. We investigated factors, from pre-conception through infant feeding practices, in relation to subsequent BBD risk in young women. The Growing Up Today Study (GUTS) includes 9032 females, born 1980-1987, who completed questionnaires annually from 1996 through 2001, then 2003, 2005, 2007, 2010, and 2013. In 1996, their mothers provided each participant's birth weight and length, gestational age, biological father's height, and infant feeding factors (e.g., breast-fed, type of formula). In 1999, their mothers reported maternal pre-pregnancy weight and weight gain during index pregnancy. Beginning in 2005, daughters (18 years+) reported whether they had ever been diagnosed with biopsy-confirmed BBD (n = 142 cases, through 2013). Logistic regression estimated associations between early life factors and biopsy-confirmed BBD. Girls whose mother's BMI prior to pregnancy was 20-25 kg/m(2) were at lower risk of BBD as young women (OR = 0.66, p = 0.04, vs. maternal pre-pregnancy BMI < 20). Girls whose mothers gained 20 + pounds (vs. <20 pounds) during pregnancy were at lower risk (among full-term singleton births: OR = 0.48, p = 0.007, if mother gained 20-35 pounds). However, neither birth weight nor BMI at birth were associated with subsequent BBD risk. We found no evidence that infant feeding practices were linked to BBD. A healthy maternal BMI before pregnancy and sufficient weight gain during pregnancy may produce daughters at lower risk for BBD as young women. Further examination of these findings is needed.
    Full-text · Article · Nov 2015 · Breast Cancer Research and Treatment
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    [Show abstract] [Hide abstract] ABSTRACT: Background: Flavonoids inhibit the growth of colon cancer cells in vitro. In a secondary analysis of a randomized controlled trial, the Polyp Prevention Trial, a higher intake of one subclass, flavonols, was statistically significantly associated with a reduced risk of recurrent advanced adenoma. Most previous prospective studies on colorectal cancer evaluated only a limited number of flavonoid subclasses and intake ranges, yielding inconsistent results. Objective: In this study, we examined whether higher habitual dietary intakes of flavonoid subclasses (flavonols, flavones, flavanones, flavan-3-ols, and anthocyanins) were associated with a lower risk of colorectal cancer. Design: Using data from validated food-frequency questionnaires administered every 4 y and an updated flavonoid food composition database, we calculated flavonoid intakes for 42,478 male participants from the Health Professionals Follow-Up Study and for 76,364 female participants from the Nurses' Health Study. Results: During up to 26 y of follow-up, 2519 colorectal cancer cases (1061 in men, 1458 in women) were documented. Intakes of flavonoid subclasses were not associated with risk of colorectal cancer in either cohort. Pooled multivariable adjusted RRs (95% CIs) comparing the highest with the lowest quintiles were 1.04 (0.91, 1.18) for flavonols, 1.01 (0.89, 1.15) for flavones, 0.96 (0.84, 1.10) for flavanones, 1.07 (0.95, 1.21) for flavan-3-ols, and 0.98 (0.81, 1.19) for anthocyanins (all P values for heterogeneity by sex >0.19). In subsite analyses, flavonoid intake was also not associated with colon or rectal cancer risk. Conclusion: Our findings do not support the hypothesis that a higher habitual intake of any flavonoid subclass decreases the risk of colorectal cancer.
    Full-text · Article · Nov 2015 · American Journal of Clinical Nutrition

Publication Stats

10k Citations
3,182.12 Total Impact Points


  • 1996-2012
    • Harvard University
      • Department of Nutrition
      Cambridge, Massachusetts, United States
  • 1993-2012
    • Harvard Medical School
      • • Division of Nutrition
      • • Department of Medicine
      Boston, Massachusetts, United States
  • 2010
    • National Cancer Institute (USA)
      • Division of Cancer Epidemiology and Genetics
      베서스다, Maryland, United States
  • 2000-2010
    • Brigham and Women's Hospital
      • • Department of Medicine
      • • Division of Preventive Medicine
      Boston, Massachusetts, United States
  • 1998
    • Centers for Disease Control and Prevention
      • Division of Nutrition, Physical Activity, and Obesity
      Druid Hills, GA, United States
  • 1986
    • Boston University
      Boston, Massachusetts, United States