Person:

Willett, Walter

We evaluated predictors of plasma concentrations of dichlorodiphenyldichloroethylene (DDE), a metabolite of dichlorodiphenyltrichloroethane (DDT), and polychlorinated biphenyls (PCBs) in a group of 240 women, controls from a breast cancer case-control study nested in the Nurses' Health Study. We considered personal attributes such as age, serum cholesterol, region of residence, adiposity, lactation, and dietary intake. DDE levels increased 0.17 ppb/year of age ((p) = 0.0003), and PCBs increased 0.08 ppb ((p) = 0.0001). DDE and PCBs increased 0.20 ((p) = 0.02) and 0.13 ppb ((p) = 0.001), respectively, per 10 mg/dl serum cholesterol. Women living in the western United States had higher levels of DDE (mean = 11.0 ppb; (p) = 0.003), and women in the Northeast and Midwest had higher levels of PCBs (mean = 5.6 ppb; (p) = 0.0002) as compared to women from other parts of the country (mean DDE = 6.3; mean PCBs = 4. 5 ppb). Levels of DDE could not be predicted from consumption of meat, fish, poultry, dairy products, vegetables, fruits, and grains. There was a positive association between fish consumption and PCB concentrations among women in the Northeast and Midwest. Using data from the cases in the nested case-control study to assess the predictive ability of the models, we confirmed that the most reliable predictors of DDE were age and serum cholesterol, and the most important predictors of PCBs were age, serum cholesterol, and residence in the Midwest or Northeast. The null results for the majority of the food variables suggest that specific dietary factors, other than fish, are not currently a substantial contributor to human exposure to DDE and PCBs.

In a 1981 review, Doll and Peto estimated that approximately 35% of cancer deaths in the United States were potentially avoidable by the modification of diet but that this percentage might be as low as 10% or as high as 70%. Since that time, the epidemiologic literature on diet and cancer has grown greatly, as has understanding of the mechanisms of carcinogenesis. In general, this expanded literature has not provided reason to alter the Doll and Peto estimate substantially. For colon cancer, evidence has accumulated that some of the international differences that were attributed to diet are probably due to physical activity. For breast cancer, the concept that fat intake per se is the primary reason for differences in rates among countries has not been supported by prospective studies. Although several lines of evidence suggest that caloric restriction and slow growth rates may contribute importantly to the low rates of breast cancer found outside Western countries, this may not translate directly to practical means of prevention. In contrast to breast cancer, more recent data have supported a causative role for red meat in the development of colon and prostate cancers, although perhaps not entirely due to its fat content. Whereas earlier thinking about nutrition and cancer emphasized the adverse effects of fat and other components in the diet, the most compelling evidence of the last decade has indicated the importance of protective factors, largely unidentified, in fruits and vegetables. Considering the more recent evidence, it is roughly estimated that about 32% of cancer may be avoidable by changes in diet; however, it now seems unlikely that less than 20% or more than 42% of cancer deaths would be avoidable by dietary change.

OBJECTIVE: Consumption of sugar-sweetened beverages (SSBs) was related to an elevated risk of type 2 diabetes and insulin resistance in several recent studies among middle- or older-aged populations. Studies on SSB consumption and glucose intolerance among pregnant women, however, are lacking. We therefore examined the association between regular SSB consumption before pregnancy and the risk of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: This was a prospective study among 13,475 U.S. women who reported at least one singleton pregnancy between 1992 and 2001 in the Nurses' Health Study II. GDM was self-reported and validated by medical record review in a subsample. Cox proportional hazards models with multivariate adjustments were applied to examine the association of SSB consumption with GDM risk. RESULTS: During 10 years of follow-up, 860 incident GDM case subjects were identified. After adjustment for age, parity, race, physical activity, smoking, alcohol intake, prepregnancy BMI, and Western dietary pattern, intake of sugar-sweetened cola was positively associated with the risk of GDM, whereas no significant association was found for other SSBs and diet beverages. Compared with women who consumed <1 serving/month, those who consumed ≥5 servings/week of sugar-sweetened cola had a 22% greater GDM risk (relative risk 1.22 [95% CI 1.01–1.47]). CONCLUSIONS: Findings from this study suggest that prepregnancy higher consumption of sugar-sweetened cola (≥5 servings/week) is associated with an elevated GDM risk, whereas no significant association with GDM risk was observed for other SSBs and diet beverages.

Background: Early life exposures, including diet, have been implicated in the etiology of breast cancer. Methods: A nested case-control study was conducted among participants in the Nurses' Health Study who completed a 24-item questionnaire about diet during high school. There were 843 eligible cases diagnosed between onset of study (1976) and before the return of the high school diet questionnaire (1986), who were matched 10:1 with controls on the basis of age. Results: Women who had, during adolescence, a higher consumption of eggs, vegetable fat and fiber had a lower risk of breast cancer, whereas risk of breast cancer was increased among women who consumed more butter. Conclusions: A possible association of elements of adolescent diet with risk of breast cancer is reported, but the findings require confirmation in prospective study.

Background: Urban areas in Africa suffer a serious problem with dual burden of infectious diseases and emerging chronic diseases such as cardiovascular diseases (CVD) and diabetes which pose a serious threat to population health and health care resources. However in East Africa, there is limited literature in this research area. The objective of this study was to examine the prevalence of cardiovascular disease risk factors and their correlates among adults in Temeke, Dar es Salaam, Tanzania. Results of this study will help inform future research and potential preventive and therapeutic interventions against such chronic diseases. Methods: The study design was a cross sectional epidemiological study. A total of 209 participants aged between 44 and 66 years were included in the study. A structured questionnaire was used to evaluate socioeconomic and lifestyle characteristics. Blood samples were collected and analyzed to measure lipid profile and fasting glucose levels. Cardiovascular risk factors were defined using World Health Organization criteria. Results: The age-adjusted prevalence of obesity (BMI ≥ 30) was 13% and 35%, among men and women ((p) = 0.0003), respectively. The prevalence of abdominal obesity was 11% and 58% ((p) = 0.0001), and high WHR (men: > 0.9, women: > 0.85) was 51% and 73% ((p) = 0.002) for men and women respectively. Women had 4.3 times greater odds of obesity (95% CI: 1.9–10.1), 14.2–fold increased odds for abdominal adiposity (95% CI: 5.8–34.6), and 2.8 times greater odds of high waist-hip-ratio (95% CI: 1.4–5.7), compared to men. Women had more than three-fold greater odds of having metabolic syndrome ((p) = 0.001) compared to male counterparts, including abdominal obesity, low HDL-cholesterol, and high fasting blood glucose components. In contrast, female participants had 50% lower odds of having hypertension, compared to men (95%CI: 0.3–1.0). Among men, BMI and waist circumference were significantly correlated with blood pressure, triglycerides, total, LDL-, and HDL-cholesterol (BMI only), and fasting glucose; in contrast, only blood pressure was positively associated with BMI and waist circumference in women. Conclusion: The prevalence of CVD risk factors was high in this population, particularly among women. Health promotion, primary prevention, and health screening strategies are needed to reduce the burden of cardiovascular disease in Tanzania.

We assessed the association between a glutamine repeat polymorphism in AIB1 and breast cancer risk in a case-control study (464 cases, 624 controls) nested within the Nurses' Health Study cohort. We observed no association between AIB1 genotype and breast cancer incidence, or specific tumor characteristics. These findings suggest that AIB1 repeat genotype does not influence postmenopausal breast cancer risk among Caucasian women in the general population.

While the association of a number of risk factors, such as family history and reproductive patterns, with breast cancer has been well established for many years, work in the past 10–15 years also has added substantially to our understanding of disease etiology. Contributions of particular note include the delineation of the role of endogenous and exogenous estrogens to breast cancer risk, and the discovery and quantification of risk associated with several gene mutations (e.g. BRCA1). Although it is difficult to integrate all epidemiologic data into a single biologic model, it is clear that several important components or pathways exist. Early life events probably determine both the number of susceptible breast cells at risk and whether mutations occur in these cells. High endogenous estrogens are well established as an important cause of breast cancer, and many known risk factors appear to operate through this pathway. Estrogens (and probably other growth factors) appear to accelerate the development of breast cancer at many points along the progression from early mutation to tumor metastasis, and appear to be influential at many points in a woman's life. These data now provide a basis for a number of strategies that can reduce risk of breast cancer, although some strategies represent complex decision-making. Together, the modification of nutritional and lifestyle risk factors and the judicious use of chemopreventive agents could have a major impact on breast cancer incidence. Further research is needed in many areas, but a few specific arenas are given particular mention.

Background: Nutrients, hormones and growth factors in dairy foods may stimulate growth hormone (GH), insulin-like growth factor I (IGF-I), and raise the ratio of IGF-I to its binding protein, IGFBP-3. We conducted pilot studies in Mongolia and Massachusetts to test the extent to which milk intake raised somatotropic hormone concentrations in prepubertal children. Methods: In Ulaanbaatar, we compared plasma levels before and after introducing 710 ml daily whole milk for a month among 46 10–11 year old schoolchildren. In a randomized cross-over study in Boston, we compared plasma hormone levels of 28 6–8 year old girls after one week of drinking 710 ml lowfat (2%) milk with their hormone levels after one week of consuming a macronutrient substitute for milk. Results: After a month of drinking whole milk, Mongolian children had higher mean plasma levels of IGF-I (p less than 0.0001), IGF-I/IGFBP-3 (p less than 0.0001), and 75th percentile of GH levels (p = 0.005). After a week of drinking lowfat milk, Boston girls had small and non-significant increases in IGF-1, IGF-1/IGFBP-3 and GH. Conclusion: Milk drinking may cause increases in somatotropic hormone levels of prepubertal girls and boys. The finding that milk intake may raise GH levels is novel, and suggests that nutrients or bioactive factors in milk may stimulate endogenous GH production.

OBJECTIVE: Phobic anxiety has been associated with increased risk of cardiovascular disease (CVD), but the underlying mechanisms are poorly understood. We aimed to determine whether associations of phobic anxiety with several known markers of CVD might be contributors. RESEARCH DESIGN AND METHODS: We used a 16-point validated index (Crown-Crisp) measured in 1988 to categorize 984 women with type 2 diabetes from the Nurses' Health Study as having low, moderate, or high phobic anxiety. Groups were then compared for differences in adipokines (adiponectin and leptin), inflammatory markers (C-reactive protein and tumor necrosis factor [TNF]-α receptor II), and markers of endothelial function (sE-selectin, soluble intercellular adhesion molecule [sICAM]-1) measured on blood samples provided between 1989 and 1990. RESULTS: Higher levels of phobic anxiety were associated with higher BMI and lower education. Higher levels of phobic anxiety were also associated with higher leptin and soluble TNF-α receptor II in both crude analyses and after adjustment for potential confounders. sICAM and sE-selectin were higher in the highest tertile compared with the middle tertile, but there was no significant trend across tertiles. We found no association between phobic anxiety and adiponectin. CONCLUSIONS: High levels of phobic anxiety are associated with increased levels of leptin and inflammatory markers, which may in part explain the previously observed relationship between anxiety and other psychosocial disorders with CVD.

OBJECTIVE: The aim of this study is to investigate the intake of zinc in relation to risk of type 2 diabetes in U.S. women. RESEARCH DESIGN AND METHODS: Dietary intakes of zinc and other nutrients were assessed and updated using a validated food frequency questionnaire from 1980 to 2002 among 82,297 women who were aged 33–60 years at baseline in 1980 and followed up to 2004 in the Nurses' Health Study. RESULTS: During the 24 years of follow-up, 6,030 incident cases of type 2 diabetes were ascertained. After adjustment of lifestyle and dietary risk factors, the relative risks (RRs) (95% CI) of type 2 diabetes comparing the highest with the lowest quintiles were 0.90 (0.82–0.99) (Ptrend = 0.04) for total zinc intake and 0.92 (0.84–1.00) (Ptrend = 0.009) for dietary zinc intake from food sources, respectively. We further found an inverse association for dietary zinc to heme iron ratio. After multivariate adjustment of covariates, the RRs (95% CI) across quintiles of this ratio were 1.0 (reference), 0.93 (0.86–1.01), 0.86 (0.79–0.94), 0.82 (0.75–0.90), and 0.72 (0.66–0.80), respectively (Ptrend < 0.0001). CONCLUSIONS: Higher zinc intake may be associated with a slightly lower risk of type 2 diabetes in women. More studies are warranted to confirm this association and to explore potential mechanisms.