Biomedical subjects

W C Willett

Publications and source records attributed to W C Willett.

At least 19 recordsLinked to original sources

PubMed2006

The scientific basis for TFA regulations-is it sufficient? Comments from the USA.

We presently have definitive evidence from multiple randomized trials that trans-fatty acids (TFA) have adverse effects on blood lipids, near definitive evidence that TFA increase inflammatory markers in blood, and strong evidence from prospective epidemiologic studies that high TFA intake is associated elevated risks of coronary heart disease. Food additives should be allowed to be used only if there is reasonable certainty of no harm. Thus, the present US Food and Drug Administration position of allowing TFA in the food supply is indefensible, and large numbers of Americans are dying prematurely because of its failure to act to responsibly.

Biomarkers↗

PubMed2006

Trans fatty acids and cardiovascular disease-epidemiological data.

Prospective epidemiologic studies and case-control studies using adipose tissue analyses support a major role of trans fatty acids (TFA) in risk of coronary heart disease (CHD). The magnitude of the association with CHD is considerably stronger than for saturated fat, and is stronger than predicted by the effects of TFA on LDL and HDL cholesterol. The apparent gap between the epidemiologic findings and effects of TFA on LDL:HDL has been bridged, at least in part, by recent metabolic studies showing effects of TFA on inflammatory factors and other indicators of insulin resistance.

Adipose Tissue↗

PubMed2006

Cyclin D1 A870G polymorphism and the risk of colorectal cancer and adenoma.

Cyclin D1 (CCND1) plays a key role in cell cycle control, particularly in the transition from G1 to S phase, which is regulated by cyclin-dependent kinases. A common adenine to guanine polymorphism (A870G) in the CCND1 gene has been associated with a longer-life protein and an increased risk of colorectal cancer and adenoma in some studies. Among subjects with hereditary nonpolyposis colorectal cancer, the A870G polymorphism has also been associated with a younger age of onset of colorectal cancer. We analysed 181 colorectal cancer cases and 475 matched controls and 524 adenoma cases and 517 matched controls within women in the Nurses' Health Study (NHS) cohort, 171 colorectal cancer cases and 347 matched controls and 372 adenoma cases and 712 matched controls nested within men in the Health Professionals' Follow-Up Study (HPFS) cohort, and 258 colorectal cancer cases and 415 matched controls within men in the Physicians' Health Study (PHS) cohort to assess the risk associated with the CCND1 A870G genotype. Moreover, we assessed whether CCND1 genotype modified the effect of a sporadic (nonsyndromic) family history of colorectal cancer as well as the effect of other dietary and lifestyle risk factors for colorectal cancer and adenoma. In all cohorts combined, the CCND1 polymorphism did not show statistically significant associations to risk of colorectal cancer (odds ratio (OR) for A allele carriers, 1.04; 95% confidence interval (95% CI), 0.82-1.32) or adenoma (OR, 0.96; 95% CI, 0.79-1.18). The CCND1 A870G genotype was associated with a modest, although nonsignificantly elevated risk of colorectal cancer (OR, 1.59; 95% CI, 0.98-2.57) in women. In contrast, the polymorphism was not associated with increased risk of adenoma in either men or women. Among participants with the A870G genotype, a family history of colorectal cancer conferred a substantially greater risk of colorectal cancer in the women (P for interaction=0.06) and adenoma in the men (P for interaction=0.02). Current postmenopausal hormone (PMH) use was associated with a significant reduction in the risk of colorectal cancer and adenoma among women with the A870G genotype, whereas there was no effect of PMH use among those with the GG genotype. The CCND1 polymorphism appeared to confer a modest elevation in the risk of colorectal cancer among women. Moreover, the A870G genotype may enhance the protective effect of postmenopausal oestrogen use on the development of colorectal neoplasia.

Adenoma↗

PubMed2006

Central adiposity, regional fat distribution, and the risk of cholecystectomy in women.

PURPOSE: Whether central adiposity contributes independently of total adiposity to the risk for gall stones is inconclusive. We examined prospectively indicators of central adiposity in relation to the occurrence of gall stone disease. METHODS: We evaluated the relationship between abdominal circumference and waist to hip ratio and risk of cholecystectomy in a cohort of women who had no history of gall stone disease. As part of the Nurses' Health Study, the women reported on questionnaires their weights, heights, and waist and hip circumferences, and the occurrence of cholecystectomy. A total of 42,312 women, aged 39-66 years in 1986, who were free of prior gall stone disease, provided complete waist and hip circumference measurements in 1986. RESULTS: We documented 3197 cases of cholecystectomy during 514,283 person years of follow up. After adjusting simultaneously for regional (waist circumference or waist to hip ratio) and total adiposity (body mass index) measures as well as for other risk factors of gall stone disease, women with a height adjusted waist circumference of 36 inches or larger had a relative risk (RR) of 1.96 (95% confidence interval (CI) 1.53-2.51; p trend < 0.0001) compared with women with a height adjusted waist circumference of less than 26 inches. Waist to hip ratio was directly associated with the risk, with an RR of 1.39 (95% CI 1.16-1.66; p trend < 0.0001) for women with a waist to hip ratio of 0.86 or higher compared with women with a waist to hip ratio of less than 0.70. CONCLUSION: Abdominal circumference and waist to hip ratio were associated with an increased risk of cholecystectomy, independently of body mass index in women.

Adult↗

PubMed2005

A candidate gene approach to searching for low-penetrance breast and prostate cancer genes.

Most cases of breast and prostate cancer are not associated with mutations in known high-penetrance genes, indicating the involvement of multiple low-penetrance risk alleles. Studies that have attempted to identify these genes have met with limited success. The National Cancer Institute Breast and Prostate Cancer Cohort Consortium--a pooled analysis of multiple large cohort studies with a total of more than 5,000 cases of breast cancer and 8,000 cases of prostate cancer--was therefore initiated. The goal of this consortium is to characterize variations in approximately 50 genes that mediate two pathways that are associated with these cancers--the steroid-hormone metabolism pathway and the insulin-like growth factor signalling pathway--and to associate these variations with cancer risk.

Breast Neoplasms↗

PubMed2005

Dietary carbohydrates and glycaemic load and the incidence of symptomatic gall stone disease in men.

BACKGROUND: Diets with a high glycaemic response exacerbate the metabolic consequences of the insulin resistance syndrome. Their effects on the incidence of gall stone disease are not clear, particularly in men. METHODS: Dietary information was collected as part of the Health Professionals Follow up Study starting in 1986 using a semiquantitative food frequency questionnaire with follow up until 1998. On biennial questionnaires participants reported new symptomatic gall stone disease, diagnosed by radiology, and whether they had undergone cholecystectomy. RESULTS: During 12 years of follow up, we documented 1810 new cases of symptomatic gall stones. After adjusting for age and other known or suspected risk factors in multivariate models, the relative risk (RR) for the highest compared with the lowest quintile of carbohydrate intake was 1.59 (95% confidence interval (CI) 1.25, 2.02; p for trend = 0.002). The RR for the highest compared with the lowest quintile of dietary glycaemic load was 1.50 (95% CI 1.20, 1.88; p for trend = 0.0008), and 1.18 for dietary glycaemic index (95% CI 1.01, 1.39; p for trend = 0.04). Independent positive associations were also seen for intakes of starch, sucrose, and fructose. CONCLUSIONS: Our findings suggest that a high intake of carbohydrate, glycaemic load, and glycaemic index increases the risk of symptomatic gall stone disease in men. These results add to the concern that low fat high carbohydrate diets may not be an optimal dietary recommendation.

Adult↗

PubMed2005

Bidi and cigarette smoking and risk of acute myocardial infarction among males in urban India.

Death from myocardial infarction (MI) in India is exacerbated by smoking of bidis or cigarettes. Smoking among 309 men with incident MI was compared to 618 age matched controls; 56% of the individuals with MI and 26% of controls were current smokers. Current smokers had a relative risk of 4.7 (95% confidence interval (CI) 3.2 to 6.9) compared to never smokers. Relative risks for smoking more than 10 cigarettes or 10 bidis daily were 9.1 (95% CI 4.7 to 17.7) and 8.1 (95% CI 4.3 to 15.3), respectively. It is estimated that smoking may cause 53% (95% CI 47% to 64%) of MIs among urban males in India.

Adult↗

PubMed2004

Vitamin D intake and incidence of multiple sclerosis.

BACKGROUND: A protective effect of vitamin D on risk of multiple sclerosis (MS) has been proposed, but no prospective studies have addressed this hypothesis. METHODS: Dietary vitamin D intake was examined directly in relation to risk of MS in two large cohorts of women: the Nurses' Health Study (NHS; 92,253 women followed from 1980 to 2000) and Nurses' Health Study II (NHS II; 95,310 women followed from 1991 to 2001). Diet was assessed at baseline and updated every 4 years thereafter. During the follow-up, 173 cases of MS with onset of symptoms after baseline were confirmed. RESULTS: The pooled age-adjusted relative risk (RR) comparing women in the highest quintile of total vitamin D intake at baseline with those in the lowest was 0.67 (95% CI = 0.40 to 1.12; p for trend = 0.03). Intake of vitamin D from supplements was also inversely associated with risk of MS; the RR comparing women with intake of >or=400 IU/day with women with no supplemental vitamin D intake was 0.59 (95% CI = 0.38 to 0.91; p for trend = 0.006). No association was found between vitamin D from food and MS incidence. CONCLUSION: These results support a protective effect of vitamin D intake on risk of developing MS.

Adolescent↗

PubMed2004

Association of weight change, weight control practices, and weight cycling among women in the Nurses' Health Study II.

OBJECTIVE: To assess the association of weight cycling with weight change, weight control practices, and bulimic behaviors. METHODS: A nested study of 2476 young and middle-aged women in the Nurses' Health Study II who provided information on intentional weight losses between 1989 and 1993. SAMPLE: In total, 224 women who were severe cyclers, 741 women who were mild cyclers, 967 age- and BMI-matched controls (noncyclers), and 544 women who did not weight cycle and maintained their weight between 1989 and 1993 completed a questionnaire in 2000-2001 assessing recent intentional weight losses, weight control practices, and weight concerns. RESULTS: After controlling for age and body mass index (BMI) in 1993, when weight cycling was initially assessed, mild cyclers gained an average of 6.7 pounds (lbs) more and severe cyclers gained approximately 10.3 lbs more than noncyclers between 1993 and 2001. Weight cyclers preferred to change their diet rather than to exercise to control their weight. Severe weight cyclers were less likely than noncyclers to use frequent exercise as a weight control strategy (odds ratio [OR]=0.8, 95% confidence interval (CI) 0.6-1.1). Cyclers were also more likely than noncyclers to engage in binge eating (mild cyclers: OR=1.8, 95% CI 1.4-2.4; and severe cyclers: OR=2.5, 95% CI 1.7-3.5). Independent of weight cycling status, age, and BMI, women who engaged in binge eating gained approximately 5 lbs more than their peers (P<0.001). CONCLUSIONS: Weight cycling was associated with greater weight gain, less physical activity, and a higher prevalence of binge eating. Low levels of activity and binge eating may be partially responsible for the large amount of weight regained by weight cyclers.

Adult↗

PubMed2004

Changes in intake of fruits and vegetables in relation to risk of obesity and weight gain among middle-aged women.

OBJECTIVE: To examine the changes in intake of fruits and vegetables in relation to risk of obesity and weight gain among middle-aged women. DESIGN: Prospective cohort study with 12 y of follow-up conducted in the Nurses' Health Study. SUBJECTS: A total of 74,063 female nurses aged 38-63 y, who were free of cardiovascular disease, cancer, and diabetes at baseline in 1984. MEASUREMENTS: Dietary information was collected using a validated food frequency questionnaire, and body weight and height were self-reported. RESULTS: During the 12-y follow-up, participants tended to gain weight with aging, but those with the largest increase in fruit and vegetable intake had a 24% of lower risk of becoming obese (BMI> or =30 kg/m2) compared with those who had the largest decrease in intake after adjustment for age, physical activity, smoking, total energy intake, and other lifestyle variables (relative risk (RR), 0.76; 95% confidence interval (CI), 0.69-0.86; P for trend <0.0001). For major weight gain (> or =25 kg), women with the largest increase in intake of fruits and vegetables had a 28% lower risk compared to those in the other extreme group (RR, 0.72; 95% CI, 0.55-0.93; P=0.01). Similar results were observed for changes in intake of fruits and vegetables when analyzed separately. CONCLUSIONS: Our findings suggest that increasing intake of fruits and vegetables may reduce long-term risk of obesity and weight gain among middle-aged women.

Adult↗

PubMed2003

Aspirin use and lung cancer in men.

We examined prospectively the relation between regular aspirin use and lung cancer risk in the Health Professionals Follow-Up Study. Of 49,383 US men aged 40-75 years who completed biennial self-administered questionnaires that assessed aspirin use beginning in 1986, 328 developed lung cancer during 601,453 person-years of follow-up through 31 December 2000. No information on aspirin dose was available. Controlling for current age, smoking status, and age at starting to smoke regularly, the relative risk (RR) of total lung cancer for regular users of aspirin (twice or more per week) at baseline compared to nonusers was 1.13 (95% confidence interval (CI) =0.89-1.43). Results were similar for non-small-cell lung cancer (RR=1.16; 95% CI=0.88-1.54). No apparent dose-dependent association was observed for the frequency of aspirin use and lung cancer risk (P for trend=0.64), and results remained null when consistent use of aspirin over time was examined. These findings do not suggest that regular aspirin use is associated with a reduced lung cancer risk.

Adult↗

PubMed2003

Processed meat intake and incidence of Type 2 diabetes in younger and middle-aged women.

AIM/HYPOTHESIS: The aim of this study was to investigate the association between processed and other meat intake and incidence of Type 2 diabetes in a large cohort of women. METHODS: Incident cases of Type 2 diabetes were identified during 8 years of follow-up in a prospective cohort study of 91246 U.S. women aged 26 to 46 years and being free of diabetes and other major chronic diseases at baseline in 1991. RESULTS: We identified 741 incident cases of confirmed Type 2 diabetes during 716276 person-years of follow-up. The relative risk adjusted for potential non-dietary confounders was 1.91 (95% CI: 1.42-2.57) in women consuming processed meat five times or more a week compared with those consuming processed meat less than once a week ( p<0.001 for trend). Further adjustment for intakes of magnesium, cereal fibre, glycaemic index, and caffeine or for a Western dietary pattern did not appreciably change the results and associations remained strong after further adjustment for fatty acid and cholesterol intake. Frequent consumption of bacon, hot dogs, and sausage was each associated with an increased risk of diabetes. While total red meat (beef or lamb as main dish, pork as main dish, hamburger, beef, pork or lamb as sandwich or mixed dish) intake was associated with an increased risk of diabetes, this association was attenuated after adjustment for magnesium, cereal fiber, glycaemic index, and caffeine (relative risk: 1.44; 95% CI: 0.92-2.24). CONCLUSION/INTERPRETATION: Our data suggest that diets high in processed meats could increase the risk for developing Type 2 diabetes.

Adult↗

PubMed2003

Physical activity and risk of breast cancer in premenopausal women.

Physical activity appears to be inversely related to risk of breast cancer, yet the results remain inconsistent. To evaluate this relation among premenopausal women and examine variation in risk according to level of obesity and use of oral contraceptives (OCs), the authors examined data from the Nurses' Health Study II. During 10 years of follow-up, 849 cases of invasive premenopausal breast cancer were confirmed. Physical activity was assessed by self-report at baseline and during follow-up using a validated questionnaire. Total physical activity was unrelated to risk of breast cancer. Women engaging in >or=27 metabolic equivalent (MET)-h week(-1) had a multivariate-adjusted relative risk (RR) of 1.04 (95% confidence interval (CI) 0.82-1.33) compared to those in the <3 MET-h week(-1) category. Among women with a BMI >or=30 kg m(-2), we observed a significant positive dose-response relation (P=0.04). Activity was unrelated to breast cancer risk at lower levels of BMI. A test for interaction between activity and BMI (<30, >or=30 kg m(-2)) was statistically significant (P=0.02). Among current OC users, higher activity was associated with a non-significantly lower risk of breast cancer (RR=0.59, 95% CI 0.30-1.16 for >or=27 vs <9 MET-h week(-1), P for linear trend=0.14). These results show no overall association between physical activity and risk of breast cancer among premenopausal women, but suggest that the effect of physical activity could be substantially modified by the underlying degree of adiposity. The potential interactions between physical activity, adiposity, and current use of OCs require further study.

Adult↗

PubMed2003

Dietary intakes of vitamins A, C, and E and risk of melanoma in two cohorts of women.

Within the two Nurses' Health Study cohorts of US women, we examined whether higher intakes of vitamin C, vitamin E, retinol, or individual tocopherols or carotenoids are associated with a lower risk of melanoma. We confirmed 414 cases of invasive melanoma among over 162,000 Caucasian women aged 25-77 years during more than 1.6 million person-years of follow-up. Diet was measured every 4 years with a food frequency questionnaire and supplement use was reported every 2 years. Several measures of sun sensitivity were assessed and included in proportional hazards models. We found that vitamins A, C, E and their individual components were not associated with a lower risk of melanoma. Only retinol intake from foods plus supplements appeared protective within a subgroup of women who were otherwise at low risk based on nondietary factors (relative risk (RR)=0.39, 95% confidence interval (CI) 0.22-0.71 for >/=1,800 vs 400 microg day(-1), P for linear trend=0.01). Contrary to expectation, we observed higher risks of melanoma with greater intakes of vitamin C from food only (RR=1.43, 95% CI 1.01-2.00 for >/=175 vs <90 mg day(-1), P for linear trend=0.05) and a significant positive dose-response with frequency of orange juice consumption (P=0.008). Further research is needed to determine whether another component in foods such as orange juice may contribute to an increase in risk.

Adult↗

PubMed2003

Prospective assessment of exclusive breastfeeding in relation to weight change in women.

OBJECTIVE: To study prospectively the relation of parity, prepregnancy body mass index (BMI), and exclusive breastfeeding to weight gain. DESIGN: The cohort of the Nurse's Health Study II, with analysis restricted to women who were aged 24 to 40 y at baseline (1989), who had a history of no more than one past full-term pregnancy at baseline, gave birth to one child between 1990 and 1991, but had no other pregnancies during the follow-up. SUBJECTS: 1538 of the 33 082 nulliparous women and 2810 of the 20 261 primiparous, in 1989. MEASUREMENTS: Introduction of daily formula/milk was assumed to represent the end of exclusive breastfeeding period. Duration of exclusive breastfeeding was categorized into 0, 1-3, 4-7, 8-11, and 12 months or more. RESULTS: After adjusting for age, physical activity, and BMI in 1989, lactation was associated with a weight gain from 1989 to 1993 of approximately 1 kg (statistically significant only for women nulliparous in 1989 with a BMI <25 kg/m(2) (P=0.02) and for those women primiparous in 1989, with a BMI >/=25 kg/m(2) (P=0.04)) comparing women who breastfed with women who did not, and duration of lactation was unrelated to the magnitude of weight change (P>0.40 for all comparisons). CONCLUSIONS: Although promotion of breastfeeding has high priority because of its enormous advantages for a newborn child, the associated maternal weight reduction is minimal. Dietary guidelines for pregnant and breastfeeding women should include ways to prevent weight retention after parity.

Adult↗

PubMed2002

Intakes of vitamins E and C, carotenoids, vitamin supplements, and PD risk.

BACKGROUND: Oxidative damage has been implicated in the pathogenesis of PD. Limited and mostly retrospective epidemiologic data suggest a reduction or no change in risk of PD associated with high vitamin E intake. OBJECTIVE: To examine prospectively the associations between intakes of vitamins E and C, carotenoids, vitamin supplements, and risk of PD. METHODS: The authors documented the occurrence of PD within two large cohorts of men and women who completed detailed and validated semiquantitative food frequency questionnaires. A total of 371 incident PD cases were ascertained in the Nurses' Health Study, which comprised 76,890 women who were followed for 14 years, and the Health Professionals Follow-Up Study, which comprised 47,331 men who were followed for 12 years. RESULTS: Neither intake of total vitamins E or C or use of vitamin E or vitamin C supplements or multivitamins was significantly associated with risk of PD. The risk of PD, however, was significantly reduced among men and women with high intake of dietary vitamin E (from foods only). The pooled multivariate relative risk (RR) comparing individuals in the highest quintile with those in the lowest quintile was 0.68 (95% CI, 0.49 to 0.93). Consumption of nuts was also significantly associated with a reduced risk of PD (for >or=5/week vs <1/month, pooled RR, 0.57; 95% CI, 0.34 to 0.95). Intakes of dietary vitamin C and carotenoids were not significantly associated with risk of PD. CONCLUSIONS: Use of vitamin supplements and high intake of carotenoids do not appear to reduce the risk of PD. The reduction in risk of PD associated with high dietary vitamin E intake suggests that other constituents of foods rich in vitamin E may be protective. Alternatively, moderate amounts of vitamin E may reduce risk of PD, but this benefit may be lost with higher intakes.

Adult↗

PubMed2002

A prospective study of the relationship between body mass index and cataract extraction among US women and men.

BACKGROUND: Obesity may influence several physiologic processes involved in cataract formation such as oxidative stress, glycosylation and osmotic stress. OBJECTIVE: To examine the association between increased body mass index (BMI) and the incidence of cataract extraction. DESIGN AND SETTING: The Nurses' Health Study and the Health Professionals Follow-up Study, both prospective cohort studies of US women and men. SUBJECTS: A total of 87 682 women and 45 549 men aged 45 y and older who did not have diagnosed cataract or cancer at baseline (1980 for women, 1986 for men). MEASUREMENTS: Cataract extractions occurring between baseline and 1996, confirmed by medical records. RESULTS: During 16 y of follow-up in the women, and 10 y in the men, (1 097 997 person-y), 4430 incident cases were documented. Compared to participants with BMI less than 23 kg/m(2), those with BMI greater than or equal to 30 kg/m(2) had 36% higher risk of any type of cataract (pooled multivariate relative risk (RR), 1.36; 95% CI, 1.23-1.49) after adjusting for smoking, age and lutein/zeaxanthin intake. The association was strongest for posterior subcapsular (PSC) cataract (pooled multivariate RR, 1.99; 95% CI, 1.55-2.55). With adjustment for diabetes, the RR of obesity associated with posterior subcapsular cataract was 1.68 (95% CI, 1.30-2.17). Obesity was not significantly associated with nuclear cataract. CONCLUSION: Obesity increases the risk of developing cataract overall, and of PSC cataract in particular; the etiology of PSC cataract may be mediated at least in part by glucose intolerance and insulin resistance, even in the absence of clinical diabetes.

Aged↗

PubMed2002

Dietary fat plays a major role in obesity: no.

The percentage of dietary energy from fat has been suggested to be an important determinant of body fat, and this presumed effect has been invoked to justify the general promotion of low-fat diets. Dietary fat and the prevalence of obesity are lower in poor countries than in affluent countries. However, these contrasts are seriously confounded by differences in physical activity and food availability; within areas of similar economic development, per capita intake of fat and the prevalence of obesity have not been positively correlated. Randomized trials are the preferable method for evaluating the effect of dietary fat on adiposity because they avoid problems of confounding that are difficult to control in other studies. In short-term trials, a small reduction in body weight is typically seen in individuals randomized to diets with a lower percentage of calories from fat. In a meta-analysis of these trials, it was estimated that a decrease in 10% of energy from fat would reduce weight by 16 g d-1, which would correspond to a 9-kg weight loss by 18 months. However, compensatory mechanisms appear to operate because in trials lasting one year or longer, fat consumption within the range of 18-40% of energy has consistently had little, if any, effect on body fatness. Moreover, within the United States (US), a substantial decline in the percentage of energy from fat during the last two decades has corresponded with a massive increase in obesity, and similar trends are occurring in other affluent countries. Diets high in fat do not account for the high prevalence of excess body fat in Western countries; reductions in the percentage of energy from fat will have no important benefits and could further exacerbate this problem. The emphasis on total fat reduction has been a serious distraction in efforts to control obesity and improve health in general.

Adaptation, Physiological↗