Hormonal and reproductive factors and risk of postmenopausal thyroid cancer in the NIH-AARP Diet and Health Study.

BACKGROUND: Worldwide, thyroid cancer incidence rates are higher among women than men. While this suggests a possible etiologic role of female sex hormones, clear associations between hormonal and reproductive factors and thyroid cancer have not been observed. However, few large prospective studies have been conducted. METHODS: Hazard ratios (HRs) and 95% confidence intervals (CIs) for hormonal and reproductive factors and incident thyroid cancer were estimated using Cox regression methods in the prospective US NIH-AARP Diet and Health Study. Between 1995 and 2006, 312 first primary incident thyroid cancers were diagnosed among 187,865 postmenopausal women ages 50-71 at baseline. RESULTS: Thyroid cancer was not associated with ages at menarche or menopause, menopause type, or parity. Oral contraceptive use for ≥10 years (vs. never use) was inversely associated with thyroid cancer risk (HR, 0.48; 95%CI, 0.28-0.84; P(trend)=0.01). Women who reported current menopausal hormone therapy at baseline had an increased thyroid cancer risk vs. never users (HR 1.38; 95% CI: 1.07-1.79) but there was no trend with increasing duration of use. Women with benign breast disease (BBD) had a significantly higher thyroid cancer risk vs. women without BBD (HR, 1.47; 95% CI, 1.09-1.99). CONCLUSIONS: Our results do not support a strong role for female hormonal and reproductive factors including ages at menarche and menopause, type of menopause or parity, in thyroid cancer etiology among postmenopausal women. Compared with previous studies, no clear patterns emerge for exogenous hormone use but further analysis in large, prospective populations may be informative. The HR for BBD is consistent with the one previous prospective analysis that examined this association.

Alcohol consumption and risk of renal cell cancer: the NIH-AARP diet and health study.

BACKGROUND: The effect of moderate to heavy drinking (>15 g per day) on renal cell cancer (RCC) risk is unclear. METHOD: The relationship between alcohol consumption and RCC was examined in the NIH-AARP Diet and Health Study (n=49 2187, 1814 cases). RESULTS: Compared with >0 to <5 g per day of alcohol consumption, the multivariate relative risk (95% confidence intervals) for 15 to <30 and 30 g per day was, 0.75 (0.63-0.90) and 0.71 (0.59-0.85), respectively, in men and 0.67 (0.42-1.07) and 0.43 (0.22-0.84), respectively, in women. CONCLUSION: Alcohol consumption was inversely associated with RCC in a dose-response manner. The inverse association may be extended to 30 g per day of alcohol intake.

Serum cytokine concentrations, flavonol intake and colorectal adenoma recurrence in the Polyp Prevention Trial.

BACKGROUND: Serum cytokine concentrations may reflect inflammatory processes occurring during the development of colorectal neoplasms. Flavonols, bioactive compounds found in plant-based foods and beverages, may inhibit colorectal neoplasms partly by attenuating inflammation. METHODS: Using logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) to investigate the association between serum concentrations of interleukin (IL) ß, 2, 8, 10, 12p70, granulocyte macrophage colony stimulating factor, interferon-γ, and tumour necrosis factor-α, measured over time, flavonol intake, estimated from a flavonol database used in conjunction with a food frequency questionnaire, and adenoma recurrence in 872 participants from the intervention arm of the Polyp Prevention Trial. RESULTS: Decreased IL-2 concentration during the trial increased the risk of any adenoma recurrence (4th vs 1st quartile, OR=1.68, 95% CI=1.13-2.49), whereas decreased IL-1ß or IL-10 reduced the risk of advanced adenoma recurrence (OR=0.37, 95% CI=0.15-0.94; OR=0.39, 95% CI=0.15-0.98, respectively). Individuals with flavonol intake above the median (29.7 mg per day) and decreased cytokine concentrations had the lowest risk of advanced adenoma recurrence. CONCLUSION: Overall, no consistent associations were observed between serum cytokine profile and colorectal adenoma recurrence; however, decreased cytokine concentrations during high flavonol consumption may indicate prevention of colorectal neoplasms.

Physical activity, sedentary behaviours, and the prevention of endometrial cancer.

Physical activity has been hypothesised to reduce endometrial cancer risk, but this relationship has been difficult to confirm because of a limited number of prospective studies. However, recent publications from five cohort studies, which together comprise 2663 out of 3463 cases in the published literature for analyses of recreational physical activity, may help resolve this question. To synthesise these new data, we conducted a meta-analysis of prospective studies published through to December 2009. We found that physical activity was clearly associated with reduced risk of endometrial cancer, with active women having an approximately 30% lower risk than inactive women. Owing to recent interest in sedentary behaviour, we further investigated sitting time in relation to endometrial cancer risk using data from the NIH-AARP Diet and Health Study. We found that, independent of the level of moderate-vigorous physical activity, greater sitting time was associated with increased endometrial cancer risk. Thus, limiting time in sedentary behaviours may complement increasing level of moderate-vigorous physical activity as a means of reducing endometrial cancer risk. Taken together with the established biological plausibility of this relation, the totality of evidence now convincingly indicates that physical activity prevents or reduces risk of endometrial cancer.

Male predominance of upper gastrointestinal adenocarcinoma cannot be explained by differences in tobacco smoking in men versus women.

BACKGROUND: Adenocarcinomas of the upper gastrointestinal tract (UGI) show remarkable male predominance. As smoking is a well-established risk factor, we investigated the role of tobacco smoking in the male predominance of UGI adenocarcinomas in the United States NIH-AARP Diet and Health Study. METHOD: A questionnaire was completed by 281,422 men and 186,133 women in 1995-1996 who were followed until 31st December 2003. Incident UGI adenocarcinomas were identified by linkage to state cancer registries. We present age-standardised cancer incidence rates per 100,000-person years and male/female ratios (M/F) calculated from age-adjusted Cox proportional hazards models, both with 95% confidence intervals (CI). RESULTS: After 2013,142-person years follow-up, 338 adenocarcinomas of the oesophagus, 261 of gastric cardia and 222 of gastric non-cardia occurred in men. In women, 23 tumours of oesophagus, 36 of gastric cardia and 88 of gastric non-cardia occurred in 1351,958-person years follow-up. The age-standardised incidence rate of all adenocarcinoma sites was 40.5 (37.8-43.3) and 11.0 (9.2-12.8) in men and women, respectively. Among smokers, the M/F of all UGI adenocarcinomas was 3.4 (2.7-4.1), with a M/F of 7.3 (4.6-11.7) for tumours in oesophagus, 3.7 (2.5-5.4) for gastric cardia and 1.7 (1.2-2.3) for gastric non-cardia. In non-smokers, M/F ratios were 14.2 (5.1-39.5) for oesophagus, 6.1 (2.6-14.7) for gastric cardia and 1.3 (0.8-2.0) for gastric non-cardia. The overall M/F ratio was 3.0 (2.2-4.3). CONCLUSION: The male predominance was similar in smokers and non-smokers for these cancer sites. These results suggest that the male predominance of upper GI adenocarcinomas cannot be explained by differences in smoking histories.

Physical activities and future risk of Parkinson disease.

OBJECTIVE: To prospectively investigate the relationship between physical activity and Parkinson disease (PD). METHODS: We evaluated physical activity in relation to PD among 213,701 participants of the NIH-AARP Diet and Health Study cohort. Physical activities over 4 periods (ages 15-18, 19-29, and 35-39, and in the past 10 years) were noted in 1996-1997, and physician-diagnosed PD was reported on the 2004-2006 follow-up questionnaire. Only cases diagnosed after 2000 (n = 767) were included in the analyses. RESULTS: Higher levels of moderate to vigorous activities at ages 35-39 or in the past 10 years as reported in 1996-1997 were associated with lower PD occurrence after 2000 with significant dose-response relationships. The multivariate odds ratios (OR) between the highest vs the lowest levels were 0.62 (95% CI confidence interval [CI] 0.48-0.81, p for trend 0.005) for ages 35-39 and 0.65 (95% CI 0.51-0.83, p for trend 0.0001) for in the past 10 years. Further analyses showed that individuals with consistent and frequent participation in moderate to vigorous activities in both periods had approximately a 40% lower risk than those who were inactive in both periods. Moderate to vigorous activities at earlier ages or light activities were not associated with PD. Finally, the association between higher moderate to vigorous physical activities and lower PD risk was demonstrated in a metaanalysis of prospective studies. CONCLUSIONS: Although we cannot exclude the possibility that less participation in physical activity is an early marker of PD, epidemiologic evidence suggests that moderate to vigorous exercise may protect against PD.

Tea, coffee, carbonated soft drinks and upper gastrointestinal tract cancer risk in a large United States prospective cohort study.

The authors investigated the relationship between hot tea, iced tea, coffee and carbonated soft drinks consumption and upper gastrointestinal tract cancers risk in the NIH-AARP Study. During 2,584,953 person-years of follow-up on 481,563 subjects, 392 oral cavity, 178 pharynx, 307 larynx, 231 gastric cardia, 224 gastric non-cardia cancer, 123 Oesophageal Squamous Cell Carcinoma (ESCC) and 305 Oesophageal Adenocarcinoma (EADC) cases were accrued. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated by multivariate-adjusted Cox regression. Compared to non-drinking, the hazard ratio for hot tea intake of > or =1 cup/day was 0.37 (95% CI: 0.20, 0.70) for pharyngeal cancer. The authors also observed a significant association between coffee drinking and risk of gastric cardia cancer (compared to <1 cup/day, the hazard ratio for drinking >3 cups/day was 1.57 (95% CI: 1.03, 2.39)), and an inverse association between coffee drinking and EADC for the cases occurring in the last 3 years of follow-up (compared to <1 cup/day, the hazard ratio for drinking >3 cups/day was 0.54 (95% CI: 0.31, 0.92)), but no association in earlier follow-up. In summary, hot tea intake was inversely associated with pharyngeal cancer, and coffee was directly associated with gastric cardia cancer, but was inversely associated with EADC during some follow-up periods.

Smoking duration, intensity, and risk of Parkinson disease.

OBJECTIVE: To evaluate the relative importance of smoking duration vs intensity in reducing the risk of Parkinson disease (PD). METHODS: The study included 305,468 participants of the NIH-AARP Diet and Health cohort, of whom 1,662 had a PD diagnosis after 1995. We estimated odds ratios (OR) and 95% confidence intervals from multivariate logistic regression models. RESULTS: Compared with never smokers, the multivariate ORs were 0.78 for past smokers and 0.56 for current smokers. Among past smokers, a monotonic trend toward lower PD risk was observed for all indicators of more smoking. Stratified analyses indicated that smoking duration was associated with lower PD risk within fixed intensities of smoking. For example, compared with never smokers, the ORs among past smokers who smoked >20 cigarettes/day were 0.96 for 1-9 years of smoking, 0.78 for 10-19 years, 0.64 for 20-29 years, and 0.59 for 30 years or more (p for trend = 0.001). In contrast, at fixed duration, the typical number of cigarettes smoked per day in general was not related to PD risk. Close examination of smoking behaviors in early life showed that patients with PD were less likely to be smokers at each age period, but if they smoked, they smoked similar numbers of cigarettes per day as individuals without PD. CONCLUSIONS: This large study suggests that long-term smoking is more important than smoking intensity in the smoking-Parkinson disease relationship.

Alcohol intake and risk of thyroid cancer in the NIH-AARP Diet and Health Study.

BACKGROUND: Certain studies suggest that alcohol may reduce the risk of thyroid cancer in women, but the effect in men remains unclear. METHODS: We analysed the association between alcohol and thyroid cancer in a large (n=490 159) prospective NIH-AARP Diet and Health Study with self-reported beer, wine, and liquor intakes. RESULTS: Over 7.5 years of follow-up (median), 170 men and 200 women developed thyroid cancer. Overall, the thyroid cancer risk decreased with greater alcohol consumption (> or =2 drinks per day vs none, relative risk=0.57, 95% CI 0.36-0.89, P-trend=0.01). CONCLUSIONS: These results suggest a potential protective role for alcohol consumption in thyroid cancer.

Non-steroidal anti-inflammatory drugs and risk of gastric and oesophageal adenocarcinomas: results from a cohort study and a meta-analysis.

Use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the risk of gastric or oesophageal adenocarcinomas. We examined the association between self-reported use of aspirin or non-aspirin NSAIDs in the earlier 12 months and gastric non-cardia (N=182), gastric cardia (N=178), and oesophageal adenocarcinomas (N=228) in a prospective cohort (N=311 115) followed for 7 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) come from Cox models adjusted for potential confounders. Use of any aspirin (HR, 95% CI: 0.64, 0.47-0.86) or other NSAIDs (0.68, 0.51-0.92) was associated with a significantly lower risk of gastric non-cardia adenocarcinoma. Neither aspirin (0.86, 0.61-1.20) nor other NSAIDs (0.91, 0.67-1.22) had a significant association with gastric cardia cancer. We found no significant association between using aspirin (1.00, 0.73-1.37) or other NSAIDs (0.90, 69-1.17) and oesophageal adenocarcinoma. We also performed a meta-analysis of the association between the use of NSAIDs and risk of gastric and oesophageal adenocarcinoma. In this analysis, aspirin use was inversely associated with both gastric and oesophageal adenocarcinomas, with summary odds ratios (95% CI) for non-cardia, cardia, and oesophageal adenocarcinomas of 0.64 (0.52-0.80), 0.82 (0.65-1.04), and 0.64 (0.52-0.79), respectively. The corresponding numbers for other NSAIDs were 0.68 (0.57-0.81), 0.80 (0.67-0.95), and 0.65 (0.50-0.85), respectively.

Associations between food patterns defined by cluster analysis and colorectal cancer incidence in the NIH-AARP diet and health study.

BACKGROUND/OBJECTIVES: To examine associations between food patterns, constructed with cluster analysis, and colorectal cancer incidence within the National Institutes of Health-AARP Diet and Health Study. SUBJECTS/METHODS: A prospective cohort, aged 50-71 years at baseline in 1995-1996, followed until the end of 2000. Food patterns were constructed, separately in men (n=293,576) and women (n=198,730), with 181 food variables (daily intake frequency per 1000 kcal) from a food frequency questionnaire. Four large clusters were identified in men and three in women. Cox proportional hazards regression examined associations between patterns and cancer incidence. RESULTS: In men, a vegetable and fruit pattern was associated with reduced colorectal cancer incidence (multivariate hazard ratio, HR: 0.85; 95% confidence interval, CI: 0.76, 0.94), when compared to less salutary food choices. Both the vegetable and fruit pattern and a fat-reduced foods pattern were associated with reduced rectal cancer incidence in men. In women, a similar vegetable and fruit pattern was associated with colorectal cancer protection (age-adjusted HR: 0.82; 95% CI: 0.70, 0.95), but the association was not statistically significant in multivariate analysis. CONCLUSIONS: These results, together with findings from previous studies support the hypothesis that micronutrient dense, low-fat, high-fiber food patterns protect against colorectal cancer.

Components of variation in serum carotenoid concentrations: the Polyp Prevention Trial.

OBJECTIVES: The intra- and interindividual variations and season and center effects were estimated from a series of serum carotenoid concentrations in the Polyp Prevention Trial (PPT) participants. SUBJECTS/METHODS: Fasting blood was collected annually for 4 years in all 1905 participants, and a subcohort of 901 participants were selected within each (of eight) center(s), by gender and dietary arm of the study, for measurement of five major carotenoid peaks. Using variance of component methods, the variation in serum carotenoid concentrations about the underlying mean was partitioned into explanatory components attributed to various sources. RESULTS: The contributions of the inter- and intraindividual variances to the overall variation in carotenoid concentrations were in the range of 61-70 and 20-35%, respectively, whereas center and center-by-season effects provided 2.6-9.5 and 0.2-1.4%, respectively. The highest percent (35%) of intraindividual variation was exhibited by lycopene, and the highest percent (70% apiece) of interindividual variation was exhibited by lutein/zeaxanthin and beta-carotene. Serum lycopene had the highest ratio of intra- to interindividual variation of 0.57, whereas lutein had the lowest ratio of 0.29. We estimate that the ratio of intra- to interindividual variance around the mean carotenoid concentration can be reduced greatly by collecting 3-4 compared to 1 blood measurement in large-scale trials like the PPT. CONCLUSION: In the largest study of components of variation in individuals at high risk for colorectal cancer, the largest contributors to variation in serum carotenoid concentrations were intra- and interindividual effects followed by center and center-by-season effects.

Index-based dietary patterns and risk of colorectal cancer: the NIH-AARP Diet and Health Study.

The authors compared how four indexes-the Healthy Eating Index-2005, Alternate Healthy Eating Index, Mediterranean Diet Score, and Recommended Food Score-are associated with colorectal cancer in the National Institutes of Health-AARP Diet and Health Study (n = 492,382). To calculate each score, they merged data from a 124-item food frequency questionnaire completed at study entry (1995-1996) with the MyPyramid Equivalents Database (version 1.0). Other variables included energy, nutrients, multivitamins, and alcohol. Models were stratified by sex and adjusted for age, ethnicity, education, body mass index, smoking, physical activity, and menopausal hormone therapy (in women). During 5 years of follow-up, 3,110 incident colorectal cancer cases were ascertained. Although the indexes differ in design, a similarly decreased risk of colorectal cancer was observed across all indexes for men when comparing the highest scores with the lowest: Healthy Eating Index-2005 (relative risk (RR) = 0.72, 95% confidence interval (CI): 0.62, 0.83); Alternate Healthy Eating Index (RR = 0.70, 95% CI: 0.61, 0.81); Mediterranean Diet Score (RR = 0.72, 95% CI: 0.63, 0.83); and Recommended Food Score (RR = 0.75, 95% CI: 0.65, 0.87). For women, a significantly decreased risk was found with the Healthy Eating Index-2005, although Alternate Healthy Eating Index results were similar. Index-based dietary patterns that are consistent with given dietary guidelines are associated with reduced risk.

Past body mass index and risk of mortality among women.

BACKGROUND: Epidemiologic studies of body mass index (BMI) in relation to mortality commonly exclude persons with health conditions and/or a history of smoking to prevent bias resulting from illness-related weight loss ('reverse causation'). Analysis of BMI from an earlier time period may minimize reverse causation without requiring exclusion of participants based on disease or smoking history. METHODS: We prospectively examined BMI based on technician measurements of weight and height from 10 years prior to start of follow-up in relation to subsequent mortality in a cohort of 50 186 women who were 40-93 years old at baseline in 1987-1989. Deaths were ascertained through the US National Death Index. Proportional hazards regression was used to estimate hazard ratios (HRs) of mortality, adjusted for age, education, race/ethnicity, income, menopausal hormone use, smoking and physical activity. RESULTS: During 10 years of follow-up through 1997, 5201 women died. Overall, we observed a J-shaped association between BMI and mortality, with increased risk for women who were underweight, overweight or obese. The HRs and 95% confidence intervals of mortality for BMI categories of <18.5, 18.5-20.9, 21.0-23.4 (reference), 23.5-24.9, 25.0-27.4, 27.5-29.9, 30.0-34.9 and 35.0+ kg m(-2) were 1.43 (1.19, 1.72), 1.07 (0.98, 1.17), 1.00 (reference), 1.10 (1.00, 1.20), 1.20 (1.11, 1.31), 1.23 (1.11, 1.37), 1.60 (1.44, 1.77) and 1.92 (1.64, 2.24). There was little evidence that pre-existing conditions (heart disease, diabetes and/or cancer) or smoking history modified the past BMI and mortality relation (P=0.54 and 0.76). CONCLUSIONS: In this large cohort of women, BMI based on technician measurements of weight and height from 10 years prior to baseline showed increased risk for mortality across the range of overweight and obesity, regardless of disease and smoking history. Observed associations between overweight, obesity and mortality in healthy individuals may also apply to persons with a history of disease or smoking.

The effects of a high-fruit and -vegetable, high-fiber, low-fat dietary intervention on serum concentrations of insulin, glucose, IGF-I and IGFBP-3.

OBJECTIVE: To determine the effects of dietary change on serum concentrations of insulin, glucose, IGF-I and IGFBP-3. SUBJECTS: From among participants in a randomized clinical trial of men and women without a history of diabetes who were 35 years old or older and who had at least one histologically confirmed colorectal adenoma removed during a qualifying colonoscopy within the 6 months before randomization, 750 subjects were selected for this analysis. METHODS: The authors analyzed fasting serum from 375 subjects with and 375 subjects without a recurrent polyp among participants in a randomized trial of a low-fat (20% of energy), high-fiber (18 g per 1000 kcals of energy intake) and high-fruit and -vegetable (5-8 servings per day) dietary intervention. RESULTS: After 4 years of follow-up, IGF-I concentration in the intervention group (N=248) declined by 8.86 ng/ml (initial mean of 133 ng/ml) and 7.74 ng/ml (initial mean value of 139 ng/ml) in the non-intervention group (N=502). Based on an unpaired t-test, these declines were both statistically significant, but the difference between groups for the decline in IGF-I (1.12 ng/ml ((95% confidence interval, -3.24 to 5.48)) was not. After 4 years, concentrations of IGFBP-3, insulin and glucose were not statistically different from values at baseline, and there were no differences in these serum measures between the intervention and control groups. In analysis restricted to lean (body mass index <25 kg/m(2)) subjects only, however, glucose concentrations in the intervention group decreased by 0.28 mmol/l, while they increased in the control group by 0.01 mmol/l (t-test for mean differences P=0.0003) over 4 years. CONCLUSIONS: A low-fat, high-fiber, high-fruit and -vegetable dietary intervention had minimal impact on serum concentrations of insulin, glucose, IGF-I and IGFBP-3 overall, but in lean subjects the intervention resulted in a significant reduction in serum glucose concentration.

Alcohol and head and neck cancer risk in a prospective study.

We investigated the relation between head and neck cancer risk and alcohol consumption in the NIH-AARP Diet and Health Study. During 2,203,500 person-years of follow-up, 611 men and 183 women developed head and neck cancer. With moderate drinking (up to one alcoholic drink per day) as the referent group, non-drinkers showed an increased risk of head and neck cancer (men: hazard ratio (HR) 1.68, 95% confidence interval (95% CI) 1.37-2.06; women: 1.46, 1.02-2.08). Among male and female alcohol drinkers, we observed a significant dose-response relationship between alcohol consumption and risk. The HR for consuming >3 drinks per day was significantly higher in women (2.52, 1.46-4.35) than in men (1.48, 1.15-1.90; P for interaction=0.0036). The incidence rates per 100 000 person-years for those who consumed >3 drinks per day were similar in men (77.6) and women (75.3). The higher HRs observed in women resulted from lower incidence rates in the referent group: women (14.7), men (34.4). In summary, drinking >3 alcoholic beverages per day was associated with increased risk in men and women, but consumption of up to one drink per day may be associated with reduced risk relative to non-drinking.

Alcohol intake and ovarian cancer risk: a pooled analysis of 10 cohort studies.

Alcohol has been hypothesized to promote ovarian carcinogenesis by its potential to increase circulating levels of estrogen and other hormones; through its oxidation byproduct, acetaldehyde, which may act as a cocarcinogen; and by depletion of folate and other nutrients. Case-control and cohort studies have reported conflicting results relating alcohol intake to ovarian cancer risk. We conducted a pooled analysis of the primary data from ten prospective cohort studies. The analysis included 529 638 women among whom 2001 incident epithelial ovarian cases were documented. After study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated by Cox proportional hazards models, and then were pooled using a random effects model; no associations were observed for intakes of total alcohol (pooled multivariate RR=1.12, 95% CI 0.86-1.44 comparing > or =30 to 0 g day(-1) of alcohol) or alcohol from wine, beer or spirits and ovarian cancer risk. The association with alcohol consumption was not modified by oral contraceptive use, hormone replacement therapy, parity, menopausal status, folate intake, body mass index, or smoking. Associations for endometrioid, mucinous, and serous ovarian cancer were similar to the overall findings. This pooled analysis does not support an association between moderate alcohol intake and ovarian cancer risk.

Meat intake and the recurrence of colorectal adenomas.

A large multicenter randomized controlled trial was re-assessed to check whether meat intake and a reduction in its consumption are associated with recurrence of adenomatous polyps of the large bowel, which are precursors of most colorectal malignancies. All subjects (n = 1905; 958 interventions and 947 controls) had one or more histologically confirmed colorectal adenomas removed during a colonoscopy within 6 months before randomization. The subjects were followed-up for approximately 4 years after randomization and a colonoscopy for detecting adenomas was conducted at the 1st and 4th year after randomization. Dietary variables were assessed at baseline (T0) and in conjunction with annual visits at the end of the 1st (T1), 2nd (T2), 3rd (T3) and 4th (T4) years. Odds ratios using logistic regression models for meat variables were estimated based on the average intake at T0, T1, T2, T3 and T4 (prior to the T4 colonoscopy) as well as change (T0-T4) in intake. In the intervention group, the total reduction in median intake of red meat from T0 to T4 was observed by the end of 1st year itself (30 and 31% for men and women, respectively). The analysis provide no evidence to suggest that lower intake or reduction in total and in red meat consumption during a period of 4 years reduces the risk of adenoma recurrence (including multiple or advanced adenoma), whereas the data suggest that high intake of fish is associated with lower risk of adenoma recurrence.

Precision of the doubly labeled water method in a large-scale application: evaluation of a streamlined-dosing protocol in the Observing Protein and Energy Nutrition (OPEN) study.

OBJECTIVE: To evaluate whether the doubly labeled water (DLW) method is precise under conditions required for a large-scale evaluation of dietary intake instruments. DESIGN: Energy expenditure was measured in 484 subjects (main study). Subjects received one of five different weight DLW dose bottles prepared in advance of the study. A repeat energy expenditure measure was obtained in a subset of 24 subjects (substudy). DLW measures of energy expenditure were performed over a 2-week interval with urine collection at the beginning and end. SETTING: Free-living environment with three clinic visits in the Maryland suburban area of Washington, DC. SUBJECTS: A total of 484 subjects (261 men and 223 women) aged 40-69 y, 24 of whom (13 men and 11 women) participated in a substudy in which DLW was administered a second time. RESULTS: The coefficient of variation of the DLW energy expenditure measurement was 5.1%. This included a 2.9% analytical and a 4.2% physiologic variation. Based on observed initial isotopic enrichment, the preweighed dosages were optimal in 70% of the main study subjects, and 9% received a dose that was less than optimal. Only six subjects (1%) were excluded because the final isotopic enrichment was too low to conduct precise measurement. CONCLUSIONS: Use of preweighed DLW dosages did not compromise the precision of the DLW method. The DLW method is a reliable measure of energy expenditure for large-scale evaluations of dietary intake instruments.

Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women.

BACKGROUND: Obesity is associated with increased breast cancer risk among postmenopausal women. We examined whether this association could be explained by the relationship of body mass index (BMI) with serum sex hormone concentrations. METHODS: We analyzed individual data from eight prospective studies of postmenopausal women. Data on BMI and prediagnostic estradiol levels were available for 624 case subjects and 1669 control subjects; data on the other sex hormones were available for fewer subjects. The relative risks (RRs) with 95% confidence intervals (CIs) of breast cancer associated with increasing BMI were estimated by conditional logistic regression on case-control sets, matched within each study for age and recruitment date, and adjusted for parity. All statistical tests were two-sided. RESULTS: Breast cancer risk increased with increasing BMI (P(trend) =.002), and this increase in RR was substantially reduced by adjustment for serum estrogen concentrations. Adjusting for free estradiol reduced the RR for breast cancer associated with a 5 kg/m2 increase in BMI from 1.19 (95% CI = 1.05 to 1.34) to 1.02 (95% CI = 0.89 to 1.17). The increased risk was also substantially reduced after adjusting for other estrogens (total estradiol, non-sex hormone-binding globulin-bound estradiol, estrone, and estrone sulfate), and moderately reduced after adjusting for sex hormone-binding globulin, whereas adjustment for the androgens (androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone) had little effect on the excess risk. CONCLUSION: The results are compatible with the hypothesis that the increase in breast cancer risk with increasing BMI among postmenopausal women is largely the result of the associated increase in estrogens, particularly bioavailable estradiol.