Pooled results from 5 validation studies of dietary self-report instruments using recovery biomarkers for energy and protein intake.

We pooled data from 5 large validation studies of dietary self-report instruments that used recovery biomarkers as references to clarify the measurement properties of food frequency questionnaires (FFQs) and 24-hour recalls. The studies were conducted in widely differing US adult populations from 1999 to 2009. We report on total energy, protein, and protein density intakes. Results were similar across sexes, but there was heterogeneity across studies. Using a FFQ, the average correlation coefficients for reported versus true intakes for energy, protein, and protein density were 0.21, 0.29, and 0.41, respectively. Using a single 24-hour recall, the coefficients were 0.26, 0.40, and 0.36, respectively, for the same nutrients and rose to 0.31, 0.49, and 0.46 when three 24-hour recalls were averaged. The average rate of under-reporting of energy intake was 28% with a FFQ and 15% with a single 24-hour recall, but the percentages were lower for protein. Personal characteristics related to under-reporting were body mass index, educational level, and age. Calibration equations for true intake that included personal characteristics provided improved prediction. This project establishes that FFQs have stronger correlations with truth for protein density than for absolute protein intake, that the use of multiple 24-hour recalls substantially increases the correlations when compared with a single 24-hour recall, and that body mass index strongly predicts under-reporting of energy and protein intakes.

A prospective study of vitamin and mineral supplement use and the risk of upper gastrointestinal cancers.

We examined the association of use of multivitamins or single vitamin/mineral supplements with risk of four upper gastrointestinal cancers in the NIH-AARP Diet and Health Study cohort with 11 years of follow-up. After exclusions, 490,593 persons were included in our analytic cohort and 1780 upper gastrointestinal cancers were accrued. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox models with adjustment for potential confounders. We observed no significant associations between multivitamin use and risk for the four cancer outcomes in crude or adjusted models. Among individual vitamin or mineral supplements, use of iron supplements was associated with significantly lower risk of esophageal adenocarcinoma (HR = 0.68, 95% CI = 0.49 to 0.94) and a significantly increased risk of gastric noncardia adenocarcinoma (HR = 1.59, 95% CI = 1.24 to 2.05). For gastric noncardia adenocarcinoma, we saw associations with zinc use (HR = 1.28, 95% CI = 1.01 to 1.62) and vitamin C use (HR = 0.79 95% CI = 0.65 to 0.96). Calcium use, some of which was reported as antacids and used to treat reflux disease, was associated with higher risk of esophageal adenocarcinoma (HR = 1.27, 95% CI = 1.06 to 1.52) and gastric cardia adenocarcinoma (HR = 1.27, 95% CI = 1.03 to 1.56) cancers. We saw no evidence that multivitamin use was associated with reduced risk of four highly fatal upper gastrointestinal cancers, but there were some differences in risk with reported use of individual supplements.

Colorectal cancers soon after colonoscopy: a pooled multicohort analysis.

OBJECTIVE: Some individuals are diagnosed with colorectal cancer (CRC) despite recent colonoscopy. We examined individuals under colonoscopic surveillance for colonic adenomas to assess possible reasons for diagnosing cancer after a recent colonoscopy with complete removal of any identified polyps. DESIGN: Primary data were pooled from eight large (>800 patients) North American studies in which participants with adenoma(s) had a baseline colonoscopy (with intent to remove all visualised lesions) and were followed with subsequent colonoscopy. We used an algorithm based on the time from previous colonoscopy and the presence, size and histology of adenomas detected at prior exam to assign interval cancers as likely being new, missed, incompletely resected (while previously an adenoma) or due to failed biopsy detection. RESULTS: 9167 participants (mean age 62) were included in the analyses, with a median follow-up of 47.2 months. Invasive cancer was diagnosed in 58 patients (0.6%) during follow-up (1.71 per 1000 person-years follow-up). Most cancers (78%) were early stage (I or II); however, 9 (16%) resulted in death from CRC. We classified 30 cancers (52%) as probable missed lesions, 11 (19%) as possibly related to incomplete resection of an earlier, non-invasive lesion and 14 (24%) as probable new lesions. The cancer diagnosis may have been delayed in three cases (5%) because of failed biopsy detection. CONCLUSIONS: Despite recent colonoscopy with intent to remove all neoplasia, CRC will occasionally be diagnosed. These cancers primarily seem to represent lesions that were missed or incompletely removed at the prior colonoscopy and might be avoided by increased emphasis on identifying and completely removing all neoplastic lesions at colonoscopy.

Intake of fruits and vegetables and risk of pancreatic cancer in a pooled analysis of 14 cohort studies.

Fruit and vegetable intake may protect against pancreatic cancer, since fruits and vegetables are rich in potentially cancer-preventive nutrients. Most case-control studies have found inverse associations between fruit and vegetable intake and pancreatic cancer risk, although bias due to reporting error cannot be ruled out. In most prospective studies, inverse associations have been weaker and imprecise because of small numbers of cases. The authors examined fruit and vegetable intake in relation to pancreatic cancer risk in a pooled analysis of 14 prospective studies from North America, Europe, and Australia (study periods between 1980 and 2005). Relative risks and 2-sided 95% confidence intervals were estimated separately for the 14 studies using the Cox proportional hazards model and were then pooled using a random-effects model. Of 862,584 men and women followed for 7-20 years, 2,212 developed pancreatic cancer. The pooled multivariate relative risks of pancreatic cancer per 100-g/day increase in intake were 1.01 (95% confidence interval (CI): 0.99, 1.03) for total fruits and vegetables, 1.01 (95% CI: 0.99, 1.03) for total fruits, and 1.02 (95% CI: 0.99, 1.06) for total vegetables. Associations were similar for men and women separately and across studies. These results suggest that fruit and vegetable intake during adulthood is not associated with a reduced pancreatic cancer risk.

Amount of time spent in sedentary behaviors and cause-specific mortality in US adults.

BACKGROUND: Sedentary behaviors predominate modern life, yet we do not fully understand the adverse effects of these behaviors on mortality after considering the benefits of moderate-vigorous physical activity (MVPA). OBJECTIVE: We tested the hypotheses that higher amounts of overall sitting time and television viewing are positively associated with mortality and described the independent and combined effects of these sedentary behaviors and MVPA on mortality. DESIGN: In the NIH-AARP Diet and Health Study, we examined 240,819 adults (aged 50-71 y) who did not report any cancer, cardiovascular disease, or respiratory disease at baseline. Mortality was ascertained over 8.5 y. RESULTS: Sedentary behaviors were positively associated with mortality after adjustment for age, sex, education, smoking, diet, race, and MVPA. Participants who reported the most television viewing (≥7 h compared with <1 h/d) were at greater risk of all-cause (HR: 1.61; 95% CI: 1.47, 1.76), cardiovascular (HR: 1.85; 95% CI: 1.56, 2.20), and cancer (HR: 1.22; 95% CI: 1.06, 1.40) mortality after adjustment for MVPA. Overall sitting was associated with all-cause mortality. Even among adults reporting high levels of MVPA (>7 h/wk), high amounts of television viewing (≥7 h/d) remained associated with increased risk of all-cause (HR: 1.47; 95% CI: 1.20, 1.79) and cardiovascular (HR: 2.00; 95% CI: 1.33, 3.00) mortality compared with those reporting the least television viewing (<1 h/d). CONCLUSIONS: Time spent in sedentary behaviors was positively associated with mortality, and participation in high levels of MVPA did not fully mitigate health risks associated with prolonged time watching television. Adults should be encouraged to reduce time spent in sedentary behaviors, when possible, and to participate in MVPA at recommended levels. The NIH-AARP Diet and Health Study was registered at clinicaltrials.gov as NCT00340015.

Strength of the relationships between three self-reported dietary intake instruments and serum carotenoids: the Observing Energy and Protein Nutrition (OPEN) Study.

OBJECTIVE: To assess the strength of the relationships between serum carotenoids and three self-reported dietary intake instruments often used to characterize carotenoid intake in studies of diet and disease. DESIGN: Participants completed a Diet History Questionnaire (DHQ), two 24 h dietary recalls (24HR), a fruit and vegetable screener and a fasting blood draw. We derived dietary intake estimates of α-carotene, ß-carotene, cryptoxanthin, lutein, zeaxanthin and lycopene from each diet instrument and calculated sex-specific multivariate correlations between dietary intake estimates and their corresponding serum values. SETTING: Montgomery County, Maryland, USA. SUBJECTS: Four hundred and seventy women and men aged 40-69 years in the National Cancer Institute's Observing Protein and Energy Nutrition (OPEN) Study. RESULTS: Serum carotenoids correlated more strongly with the DHQ (r = 0·34-0·54 for women; r = 0·38-0·56 for men) than with the average of two recalls (r = 0·26-0·47 for women; r = 0·26-0·40 for men) with the exception of zeaxanthin, for which the correlations using recalls were higher. With adjustment for within-person variation, correlations between serum carotenoids and recalls were greatly improved (r = 0·38-0·83 for women; r = 0·42-0·74 for men). In most cases, correlations between serum carotenoids and the fruit and vegetable screener resembled serum-DHQ correlations. CONCLUSIONS: Evidence from the study provides support for the use of the DHQ, a fruit and vegetable screener and deattenuated recalls for estimating carotenoid status in studies without serum measures, and draws attention to the importance of adjusting for intra-individual variability when using recalls to estimate carotenoid values.

Coffee intake and breast cancer risk in the NIH-AARP diet and health study cohort.

There are several biologic mechanisms whereby coffee might reduce breast cancer risk. Caffeine and caffeic acid, major coffee constituents, have been shown to suppress mammary tumor formation in animal models and to inhibit DNA methylation in human breast cancer cells, respectively. Coffee may also reduce risk through decreasing inflammation and influencing estrogen metabolism. However, epidemiologic studies have been inconsistent and few studies have examined the association by estrogen and progesterone receptor (ER/PR) status. We evaluated coffee intake for its effect on incident breast cancer in the National Institutes of Health-AARP Diet and Health Study cohort, which included 198,404 women aged 50-71 with no history of cancer, who in 1995-1996 completed a questionnaire capturing usual coffee intake over the past year. State cancer registry and mortality index linkage identified 9,915 primary incident breast carcinomas through December 2006; available information on hormone receptor (HR) status identified 2,051 ER+/PR+ and 453 ER-/PR- cancers. In multivariable proportional hazards models, coffee intake was not associated with breast cancer risk (p-value for trend = 0.38; relative risk = 0.98, 95% confidence interval: 0.91-1.07, for four or more cups per day as compared to women who never drank coffee), and results did not vary by body mass index or history of benign breast biopsy (p-value for interaction > 0.10). We found no evidence of a relationship with either caffeinated or decaffeinated coffee. Null findings persisted for risk of both HR-positive and -negative breast cancers. These findings from a large prospective cohort do not support a role of coffee intake in breast carcinogenesis.

Association of dietary fat intakes with risk of esophageal and gastric cancer in the NIH-AARP diet and health study.

The aim of our study was to investigate whether intakes of total fat and fat subtypes were associated with esophageal adenocarcinoma (EAC), esophageal squamous cell carcinoma (ESCC), gastric cardia or gastric noncardia adenocarcinoma. From 1995-1996, dietary intake data was reported by 494,978 participants of the NIH-AARP cohort. The 630 EAC, 215 ESCC, 454 gastric cardia and 501 gastric noncardia adenocarcinomas accrued to the cohort. Cox proportional hazards regression was used to examine the association between the dietary fat intakes, whilst adjusting for potential confounders. Although apparent associations were observed in energy-adjusted models, multivariate adjustment attenuated results to null [e.g., EAC energy adjusted hazard ratio (HR) and 95% confidence interval (95% CI) 1.66 (1.27-2.18) p for trend <0.01; EAC multivariate adjusted HR (95% CI) 1.17 (0.84-1.64) p for trend = 0.58]. Similar patterns were also observed for fat subtypes [e.g., EAC saturated fat, energy adjusted HR (95% CI) 1.79 (1.37-2.33) p for trend <0.01; EAC saturated fat, multivariate adjusted HR (95% CI) 1.27 (0.91-1.78) p for trend = 0.28]. However, in multivariate models an inverse association for polyunsaturated fat (continuous) was seen for EAC in subjects with a body mass index (BMI) in the normal range (18.5-<25 kg/m(2)) [HR (95% CI) 0.76 (0.63-0.92)], that was not present in overweight subjects [HR (95% CI) 1.04 (0.96-1.14)], or in unstratified analysis [HR (95% CI) 0.97 (0.90-1.05)]. p for interaction = 0.02. Overall, we found null associations between the dietary fat intakes with esophageal or gastric cancer risk; although a protective effect of polyunsaturated fat intake was seen for EAC in subjects with a normal BMI.

Serum macrophage inhibitory cytokine-1 (MIC-1/GDF15): a potential screening tool for the prevention of colon cancer?

BACKGROUND: Macrophage inhibitory cytokine-1 (MIC-1/GDF15) mediates nonsteroidal anti-inflammatory drug (NSAID) protection from colonic polyps in mice and is linked to the development of colorectal carcinoma in humans. Therefore, changes in serum MIC-1/GDF15 levels could predict the presence of premalignant colonic polyposis and assist in population screening strategies. METHODS: Serum MIC-1/GDF15 levels were measured in subjects in the Polyp Prevention Trial, in which NSAID use and colon cancer risk factors were defined. Subjects had an initial adenoma removed, a repeat colonoscopy removing previously unidentified polyps, and serum MIC-1/GDF15 estimation. Three years later recurrent adenomas were identified and serum MIC-1/GDF15 levels reestimated. The relationship between serum MIC-1/GDF15 levels and adenoma presence or recurrence was examined. RESULTS: Serum MIC-1/GDF15 levels differed by adenoma status and were significantly related to colon cancer risk factors. In addition, mean serum MIC-1/GDF15 levels rose with increasing numbers of adenomas present and high-risk adenoma recurrence. NSAID users had higher serum MIC-1/GDF15 concentrations, which were related to protection from adenoma recurrence. Furthermore, adjusted serum MIC-1/GDF15 levels at final follow-up were related to adenoma recurrence (highest quartile MIC-1/GDF15; OR = 14.7, 95% CI: 3.0-73). CONCLUSIONS: These data suggest that MIC-1/GDF15 mediates at least some of the protection afforded by NSAIDs against human colonic polyposis. Furthermore, serum MIC-1/GDF15 levels vary with the development of adnenomatous colonic polyps. IMPACT: Serum MIC-1/GDF15 determination may hold promise as the first serum screening test to assist the detection of premalignant adenomatous colonic polyposis.

Epithelial ovarian cancer and exposure to dietary nitrate and nitrite in the NIH-AARP Diet and Health Study.

Ovarian cancer is a leading cause of cancer death among women in the United States and it has the highest mortality rate of all gynecologic cancers. Internationally, there is a five-fold variation in incidence and mortality of ovarian cancer, which suggests a role for environmental factors, including diet. Nitrate and nitrite are found in various food items and they are precursors of N-nitroso compounds, which are known carcinogens in animal models. We evaluated dietary nitrate and nitrite intake and epithelial ovarian cancer in the National Institutes of Health (NIH)-AARP Diet and Health Study, including 151 316 women aged 50-71 years at the time of the baseline questionnaire in 1995-1996. The nitrate and nitrite intake was assessed using a 124-item validated food frequency questionnaire. Through 31 December 2006, 709 incident epithelial ovarian cancer cases with complete dietary information were identified. Using Cox proportional hazards regression to estimate hazard ratios and 95% confidence intervals (CIs), women in the highest intake quintile of dietary nitrate had a 31% increased risk (95% CI: 1.01-1.68) of epithelial ovarian cancer, compared with those in the lowest intake quintile. Although there was no association for total dietary nitrite, those in the highest intake category of animal sources of nitrite had a 34% increased risk (95% CI: 1.05-1.69) of ovarian cancer. There were no clear differences in risk by histologic subtype of ovarian cancer. Our findings suggest that a role of dietary nitrate and nitrite in ovarian cancer risk should be followed in other large cohort studies.

Sugars in diet and risk of cancer in the NIH-AARP Diet and Health Study.

Prospective epidemiologic data on the effects of different types of dietary sugars on cancer incidence have been limited. In this report, we investigated the association of total sugars, sucrose, fructose, added sugars, added sucrose and added fructose in the diet with risk of 24 malignancies. Participants (n = 435,674) aged 50-71 years from the NIH-AARP Diet and Health Study were followed for 7.2 years. The intake of individual sugars was assessed using a 124-item food frequency questionnaire (FFQ). Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) in multivariable models adjusted for confounding factors pertinent to individual cancers. We identified 29,099 cancer cases in men and 13,355 cases in women. In gender-combined analyses, added sugars were positively associated with risk of esophageal adenocarcinoma (HR(Q5 vs. Q1) : 1.62, 95% CI: 1.07-2.45; p(trend) = 0.01), added fructose was associated with risk of small intestine cancer (HR(Q5 vs. Q1) : 2.20, 95% CI: 1.16-4.16; p(trend) = 0.009) and all investigated sugars were associated with increased risk of pleural cancer. In women, all investigated sugars were inversely associated with ovarian cancer. We found no association between dietary sugars and risk of colorectal or any other major cancer. Measurement error in FFQ-reported dietary sugars may have limited our ability to obtain more conclusive findings. Statistically significant associations observed for the rare cancers are of interest and warrant further investigation.

A prospective cohort study of obesity and risk of oesophageal and gastric adenocarcinoma in the NIH-AARP Diet and Health Study.

OBJECTIVE: The incidence of oesophageal adenocarcinoma (EAC) has increased rapidly over the past 40 years and accumulating evidence suggests that obesity, as measured by body mass index (BMI), is a major risk factor. It remains unclear whether abdominal obesity is associated with EAC and gastric adenocarcinoma. DESIGN: Cox proportional hazards regression was used to examine associations between overall and abdominal obesity with EAC and gastric adenocarcinoma among 218 854 participants in the prospective NIH-AARP cohort. RESULTS: 253 incident EAC, 191 gastric cardia adenocarcinomas and 125 gastric non-cardia adenocarcinomas accrued to the cohort. Overall obesity (BMI) was positively associated with EAC and gastric cardia adenocarcinoma risk (highest (≥35 kg/m(2)) vs referent (18.5-<25 kg/m(2)); HR 2.11, 95% CI 1.09 to 4.09 and HR 3.67, 95% CI 2.00 to 6.71, respectively). Waist circumference was also positively associated with EAC and gastric cardia adenocarcinoma risk (highest vs referent; HR 2.01, 95% CI 1.35 to 3.00 and HR 2.22, 95% CI 1.43 to 3.47, respectively), whereas waist-to-hip ratio (WHR) was positively associated with EAC risk only (highest vs referent; HR 1.81, 95% CI 1.24 to 2.64) and persisted in patients with normal BMI (18.5-<25 kg/m(2)). Mutual adjustment of WHR and BMI attenuated both, but did not eliminate the positive associations for either with risk of EAC. In contrast, the majority of the anthropometric variables were not associated with adenocarcinomas of the gastric non-cardia. CONCLUSION: Overall obesity was associated with a higher risk of EAC and gastric cardia adenocarcinoma, whereas abdominal obesity was found to be associated with increased EAC risk; even in people with normal BMI.

Dietary lignan and proanthocyanidin consumption and colorectal adenoma recurrence in the Polyp Prevention Trial.

Lignans and proanthocyanidins are plant polyphenols that have shown protective properties against colorectal neoplasms in some human studies. Using logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) to prospectively evaluate the association between lignan and proanthocyanidin intake, estimated from databases linked to a food frequency questionnaire, and adenoma recurrence in 1,859 participants of the Polyp Prevention Trial. Overall, individual or total lignans or proanthocyanidins were not associated with colorectal adenoma recurrence. However, in sex-specific analyses, total lignan intake was positively associated with any adenoma recurrence in women (highest vs. lowest lignan intake quartile OR = 2.07, 95% CI: 1.22-3.52, p trend = 0.004) but not in men (p interaction = 0.04). To conclude, dietary lignan and proanthocyanidin consumption were not generally related to colorectal adenoma recurrence; however, high lignan intake may increase the risk of adenoma recurrence in women.

Body fat distribution, weight change during adulthood, and thyroid cancer risk in the NIH-AARP Diet and Health Study.

Body mass index (BMI) has been positively associated with thyroid cancer risk in several studies, but the underlying mechanisms remain unclear. We examined the associations for waist and hip circumference and weight change during adulthood with thyroid cancer risk among 125,347 men and 72,363 women in the NIH-AARP Diet and Health Study who completed a second mailed questionnaire in 1996-1997. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated separately by sex and adjusted for race/ethnicity, education and smoking status. During follow-up (median = 10.1 years), 106 men and 105 women were diagnosed with a first primary thyroid cancer, as identified through linkage to state cancer registries. Having a large waist circumference (above the clinical cutpoint for normal: > 102 cm in men and > 88 cm in women) was associated with increased risk in both men (HR = 1.79, 95% CI: 1.21-2.63) and women (HR = 1.54, 95% CI: 1.05-2.26). Having both a large waist and BMI in the obese range (≥ 30 kg/m2) approximately doubled the risk of thyroid cancer (HR in men = 2.13, 95% CI: 1.18-3.85; HR in women = 1.91, 95% CI: 1.31-3.25) compared to having a normal waist circumference/normal BMI (18.5-24.9 kg/m2). We also observed positive association for weight gain between ages 18-35 in men (gained ≥ 10.0 kg vs. lost/gained < 5 kg, HR = 1.49, 95% CI: 0.93-2.39, p-trend = 0.03), but the association was less pronounced in women. No clear association for weight gain in later life was observed. These results support a potential role for hormonal and metabolic parameters common to central adiposity in thyroid carcinogenesis.

Health status, neighborhood socioeconomic context, and premature mortality in the United States: The National Institutes of Health-AARP Diet and Health Study.

OBJECTIVES: We examined whether the risk of premature mortality associated with living in socioeconomically deprived neighborhoods varies according to the health status of individuals. METHODS: Community-dwelling adults (n = 566,402; age = 50-71 years) in 6 US states and 2 metropolitan areas participated in the ongoing prospective National Institutes of Health-AARP Diet and Health Study, which began in 1995. We used baseline data for 565,679 participants on health behaviors, self-rated health status, and medical history, collected by mailed questionnaires. Participants were linked to 2000 census data for an index of census tract socioeconomic deprivation. The main outcome was all-cause mortality ascertained through 2006. RESULTS: In adjusted survival analyses of persons in good-to-excellent health at baseline, risk of mortality increased with increasing levels of census tract socioeconomic deprivation. Neighborhood socioeconomic mortality disparities among persons in fair-to-poor health were not statistically significant after adjustment for demographic characteristics, educational achievement, lifestyle, and medical conditions. CONCLUSIONS: Neighborhood socioeconomic inequalities lead to large disparities in risk of premature mortality among healthy US adults but not among those in poor health.

Using regression calibration equations that combine self-reported intake and biomarker measures to obtain unbiased estimates and more powerful tests of dietary associations.

The authors describe a statistical method of combining self-reports and biomarkers that, with adequate control for confounding, will provide nearly unbiased estimates of diet-disease associations and a valid test of the null hypothesis of no association. The method is based on regression calibration. In cases in which the diet-disease association is mediated by the biomarker, the association needs to be estimated as the total dietary effect in a mediation model. However, the hypothesis of no association is best tested through a marginal model that includes as the exposure the regression calibration-estimated intake but not the biomarker. The authors illustrate the method with data from the Carotenoids and Age-Related Eye Disease Study (2001--2004) and show that inclusion of the biomarker in the regression calibration-estimated intake increases the statistical power. This development sheds light on previous analyses of diet-disease associations reported in the literature.

Socioeconomic deprivation impact on meat intake and mortality: NIH-AARP Diet and Health Study.

OBJECTIVE: Previous studies have not examined potential interactions between meat intake and characteristics of the local environment on the risk of mortality. This study examined the impact of area socioeconomic deprivation on the association between meat intake and all-cause and cause-specific mortality after accounting for individual-level risk factors. METHODS: In the prospective NIH-AARP Diet and Health Study, we analyzed data from adults, ages 50-71 years at baseline (1995-1996). Individual-level dietary intake and health risk information were linked to the demographic and socioeconomic context of participants' local environment based on census tract data. Deaths (n = 33,831) were identified through December 2005. Multilevel Cox models were used to estimate hazard ratios and 95% confidence intervals for quintiles of area deprivation scores. RESULTS: Associations of red and processed meats with mortality were consistent across deprivation quintiles. Men residing in least-deprived neighborhoods had a stronger protective effect for white meat consumption. No differences by deprivation index were observed for women. CONCLUSION: Red and processed meat intake increases mortality risk regardless of level of deprivation within a given neighborhood suggesting biological mechanisms rather than neighborhood contextual factors may underlie these meat-mortality associations. The effect of white meat intake on cancer mortality was modified by area deprivation among men.

Folate intake and risk of pancreatic cancer: pooled analysis of prospective cohort studies.

BACKGROUND: Epidemiological studies evaluating the association between folate intake and risk of pancreatic cancer have produced inconsistent results. The statistical power to examine this association has been limited in previous studies partly because of small sample size and limited range of folate intake in some studies. METHODS: We analyzed primary data from 14 prospective cohort studies that included 319,716 men and 542,948 women to assess the association between folate intake and risk of pancreatic cancer. Folate intake was assessed through a validated food-frequency questionnaire at baseline in each study. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models and then pooled using a random effects model. All statistical tests were two-sided. RESULTS: During 7-20 years of follow-up across studies, 2195 pancreatic cancers were identified. No association was observed between folate intake and risk of pancreatic cancer in men and women (highest vs lowest quintile: dietary folate intake, pooled multivariable RR = 1.06, 95% CI = 0.90 to 1.25, P(trend) = .47; total folate intake [dietary folate and supplemental folic acid], pooled multivariable RR = 0.96, 95% CI = 0.80 to 1.16, P(trend) = .90). No between-study heterogeneity was observed (for dietary folate, P(heterogeneity) = .15; for total folate, P(heterogeneity) = .22). CONCLUSION: Folate intake was not associated with overall risk of pancreatic cancer in this large pooled analysis.

Fatherhood and the risk of cardiovascular mortality in the NIH-AARP Diet and Health Study.

BACKGROUND: Fertility potential and reproductive fitness may reflect a man's future health, given that over one-third of the male human genome is involved in reproduction. We sought to determine if offspring number predicts cardiovascular death in the US men. METHODS: Using data from the NIH-AARP Diet and Health Study, 137,903 men (aged 50-71) without prior cardiovascular disease were followed-up for an average of 10.2 years. International Classification of Diseases, ninth edition, codes were used to establish the cause of death, and multivariable Cox proportional hazards modeling was used to estimate the association between offspring number and cardiovascular death while accounting for sociodemographic and lifestyle characteristics. RESULTS: Almost all (92%) participants had fathered at least one child and 50% had three or more offspring. A total of 3082 men died of cardiovascular causes during follow-up for an age-adjusted incidence rate of 2.70 per 1000 person-years. Compared with fathers, after adjusting for sociodemographic and lifestyle factors, childless men had a 17% [hazard ratio (HR): 1.17; 95% confidence interval (CI): 1.03-1.32] increased risk of death from cardiovascular disease contracted in the study period, and this elevated risk appeared to extend also to men with only one child. In comparison with fathers of five or more children, adjusted relative hazards for cardiovascular mortality of this sort were 1.06 (95% CI: 0.92-1.22) for four children, 1.02 (0.90-1.16) for three children, 1.02 (0.90-1.16) for two children, 1.11 (0.95-1.30) for one child and 1.21 (1.03-1.41) for no children. CONCLUSIONS: Married men who have no children have a higher risk of dying from cardiovascular disease contracted after the age of 50 than men with two or more children.

Lifestyle factors and risk for new-onset diabetes: a population-based cohort study.

BACKGROUND: Epidemiologic data on the combined influence of several lifestyle factors on diabetes risk are rare, particularly among older adults. OBJECTIVE: To examine how combinations of lifestyle risk factors relate to the 11-year risk for incident diabetes. DESIGN: Population-based prospective cohort study. SETTING: National Institutes of Health (NIH)-AARP Diet and Health Study. PARTICIPANTS: 114,996 men and 92,483 women, aged 50 to 71 years in 1995 to 1996, without evidence of heart disease, cancer, or diabetes. MEASUREMENTS: A comprehensive survey of demographic characteristics and lifestyle factors, including dietary intake, body weight and height, physical activity, smoking, and alcohol consumption at baseline (1995 to 1996). Low-risk groups were formed by dichotomizing each lifestyle factor. Incident self-reported, physician-diagnosed diabetes was identified with a follow-up survey in 2004 to 2006. RESULTS: 11,031 men (9.6%) and 6969 women (7.5%) developed new-onset diabetes. For each additional lifestyle factor in the low-risk group, the odds for diabetes were 31% lower (odds ratio [OR], 0.69 [95% CI, 0.68 to 0.71]) among men and 39% lower (OR, 0.61 [CI, 0.60 to 0.63]) among women. Men and women whose diet score, physical activity level, smoking status, and alcohol use were all in the low-risk group had ORs for diabetes of 0.61 (CI, 0.56 to 0.66) and 0.43 (CI, 0.34 to 0.55), respectively. When absence of overweight or obesity was added, the respective ORs were 0.28 (CI, 0.23 to 0.34) and 0.16 (CI, 0.10 to 0.24) for men and women. Results did not differ by family history of diabetes or level of adiposity. LIMITATION: The study was observational, with potential for residual confounding. CONCLUSION: Lifestyle factors, when considered in combination, are associated with a substantial reduction in risk for diabetes. PRIMARY FUNDING SOURCE: The NIH-AARP Diet and Health Study was supported by the Intramural Research Program of the NIH.