Validation and Comparison of Nutrient Intakes from Two Dietary Questionnaires Developed for the Multiethnic Cohort Study.

BACKGROUND: Quantitative food frequency questionnaires (QFFQs) are often used to measure dietary intakes in large cohort studies but the impact of updating these questionnaires over time is not often examined. OBJECTIVE: This study compared nutrient intakes estimated from two different QFFQs to each other and to intakes calculated from three 24-hour dietary recalls (24HDRs). DESIGN: This study used a cross-sectional design. PARTICIPANTS/SETTING PARTICIPANTS: Participants (N = 352) were members of the Multiethnic Cohort Study from five racial and ethnic groups (African American, Japanese American, Latino American, Native Hawaiian, and White) who lived in Hawaii and Los Angeles. They were recruited in 2010 and asked to complete two QFFQs, two months apart, and three 24HDRs in the time between completion of the QFFQs. One questionnaire had been developed for a baseline survey (baseline QFFQ) at the start of the Multiethnic Cohort Study during 1993-1996, and the other was updated for a follow-up study 10 years later (10-year QFFQ). MAIN OUTCOME MEASURES: Daily intakes of energy and nine nutrients were estimated from both QFFQs, and from the average of three 24HDRs. STATISTICAL ANALYSES PERFORMED: Pearson's correlation coefficients were calculated between log-transformed nutrient intakes from each QFFQ and the 24HDRs and between the two QFFQs overall, by sex, and by race and ethnicity. RESULTS: Correlations for the 10-year QFFQ with the 24HDRs (average = 0.45) were higher than for the baseline QFFQ (average = 0.41), although the differences were not statistically significant. The increase in correlations was particularly pronounced for Native Hawaiian and African American participants. When absolute values were adjusted for energy intake, the average correlations were higher at 0.57 for the baseline QFFQ and 0.58 for the 10-year QFFQ overall and this pattern was seen in most racial and ethnic subgroups. The average correlations between the two QFFQs were 0.73 for both absolute intakes and nutrient densities overall. CONCLUSIONS: Correlations of nutrient intakes between the two QFFQs and 24HDRs were similar, and intakes from the two QFFQs were highly correlated. QFFQs updated for changes to the food supply may provide improved assessment for cohort studies that include diverse populations.

Dietary Vitamin A and Breast Cancer Risk in Black Women: The African American Breast Cancer Epidemiology and Risk (AMBER) Consortium.

BACKGROUND: Studies in women of European descent showed an inverse association of dietary vitamin A (retinol and carotenoids) intake with breast cancer risks, mainly in premenopausal women. OBJECTIVES: We examined whether higher compared with lower levels of dietary vitamin A are associated with reduced breast cancer risks among Black women by estrogen receptor (ER) and menopausal statuses. METHODS: In this pooled analysis, data were from 3564 breast cancer cases and 11,843 controls (mean ages = 56.4 and 56.3 years, respectively) in the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium. Dietary intake was assessed by FFQs. Multivariable logistic regressions were performed to estimate ORs and 95% CIs for study-specific quintiles of total vitamin A equivalents and individual carotenoids, and a pooled OR was estimated by a random-effect model. RESULTS: We observed an inverse association of total vitamin A equivalents with ER-positive breast cancer (quintiles 5 compared with 1: pooled OR: 0.82; 95% CI: 0.67-1.00; P-trend = 0.045). The association was seen among premenopausal women (pooled OR: 0.60; 95% CI: 0.43-0.83; P-trend = 0.004), but not among postmenopausal women (pooled OR: 0.99; 95% CI: 0.77-1.28; P-trend = 0.78). Additionally, there were inverse associations of dietary ß-carotene (quintiles 5 compared with 1: pooled OR: 0.70; 95% CI: 0.51-0.95; P-trend = 0.08) and lutein (pooled OR: 0.63; 95% CI: 0.45-0.87; P-trend = 0.020) with ER-positive breast cancer among premenopausal women. There was no evidence for an association of total vitamin A equivalents or individual carotenoids with ER-negative breast cancer, regardless of menopausal status. CONCLUSIONS: Our findings on dietary vitamin A and breast cancer risks in Black women are consistent with observations in women of European descent and advance the literature showing an inverse association for ER-positive disease.

Prediagnostic Neurofilament Light Chain Levels in Amyotrophic Lateral Sclerosis.

OBJECTIVE: To assess whether plasma neurofilament light chain (NfL) levels are elevated before ALS diagnosis and to evaluate whether pre-diagnostic NfL levels are associated with metabolic alterations. METHODS: We conducted a matched case-control study nested in three large prospective US cohorts (the Nurses' Health Study, the Health Professionals Follow-up Study, and the Multiethnic Cohort Study), and identified 84 individuals who developed ALS during follow-up and had available plasma samples prior to disease diagnosis. For each ALS case, we randomly selected controls from those who were alive at the time of the case diagnosis and matched on birth year, sex, race/ethnicity, fasting status, cohort, and time of blood draw. We measured NfL in the plasma samples and used conditional logistic regression to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for ALS, adjusting for body mass index, smoking, physical activity, and urate levels. RESULTS: Higher NfL levels were associated with a higher ALS risk in plasma samples collected within 5 years of the ALS diagnosis (RR per 1 standard deviation [SD] increase: 2.68, 95% CI: 1.18-6.08), but not in samples collected further away from the diagnosis (RR per 1 SD increase 1.16, 95% CI: 0.78-1.73). A total of 21 metabolites were correlated with pre-diagnostic NfL levels in ALS cases (p < 0.05), but none of these remained significant after multiple comparison adjustments. CONCLUSIONS: Plasma NfL levels were elevated in pre-diagnostic ALS cases, indicating that NfL may be a useful biomarker already in the earliest stages of the disease. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that plasma NfL levels are elevated in pre-diagnostic ALS patients.

Pre-diagnostic plasma lipid levels and the risk of amyotrophic lateral sclerosis.

OBJECTIVE: To assess whether pre-diagnostic lipid levels are associated with Amyotrophic lateral sclerosis (ALS) risk. Methods: We conducted a matched case-control study nested in five large prospective US cohorts (the Nurses' Health Study, the Health Professionals Follow-up Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort Study, and the Women's Health Initiative), and identified 275 individuals who developed ALS during follow-up and had provided blood samples before disease diagnosis. For each ALS case, we randomly selected two controls who were alive at the time of the case diagnosis and matched on cohort, birth year (±1 year), sex, race/ethnicity, fasting status, and time of blood draw. We measured total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels in the plasma samples, and used conditional logistic regression to estimate associations between lipid levels and ALS risk. Results: Higher levels of HDL-C were associated with higher ALS risk in an analysis adjusted for the matching factors (risk ratio [RR] Q4 vs. Q1: 1.78, 95% confidence interval [CI]: 1.18-2.69, p trend: 0.007). The estimate remained similar in a multivariable analysis additionally adjusted for body mass index, physical activity, smoking, alcohol intake, plasma urate levels, and use of cholesterol-lowering drugs (RR Q4 vs. Q1: 1.71, 95% CI: 1.07-2.73, p trend: 0.02). Plasma levels of TC, LDL-C, and TG were not associated with ALS risk. Conclusions: Higher pre-diagnostic HDL-C levels, but not levels of other lipids, were associated with a higher risk of ALS.

Association of serum γ-tocopherol levels with mortality: the Multiethnic Cohort Study.

BACKGROUND/OBJECTIVES: γ-Tocopherol has unique properties that protect against nitrogen oxide-mediated cellular damage. To elucidate the potential role of γ-tocopherol in the aging process, we examined the associations of serum γ-tocopherol levels with all-cause and cause-specific mortality. SUBJECTS/METHODS: Among participants in the biorepository subcohort of the Multiethnic Cohort Study, pre-cancer diagnostic serum γ-tocopherol levels were measured in a subset of 3904 men and 4461 women. Of these, 22.7% of men and 13.5% of women died during a mean follow-up time of 9.6 ± 2.6 years. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for mortality associated with γ-tocopherol were estimated by Cox proportional hazards regression. RESULTS: Positive associations of serum γ-tocopherol with all-cause, cancer, and cardiovascular disease mortality (CVD) (Ptrend < 0.05) were detected after adjusting for age, race/ethnicity, and serum cholesterol levels. The respective HRs (95% CIs) for the highest versus the lowest sex-specific γ-tocopherol quartile were 1.43 (1.17-1.74), 1.79 (1.22-2.64), and 1.52 (1.10-2.11) for men and 1.58 (1.25-2.00), 1.59 (1.05-2.41), and 1.59 (1.07-2.37) for women. Associations remained significant for all-cause mortality among women after further adjusting for smoking variables and history of cancer, CVD, diabetes, and hypertension at cohort entry (highest vs. lowest γ-tocopherol quartile: HR = 1.38; 95% CI = 1.08-1.75; Ptrend = 0.005). Overall, associations with all-cause mortality were consistent across race/ethnicity and were significant in three of ten sex-specific racial/ethnic groups in the fully adjusted models, with no interactions between ethnicity and γ-tocopherol. CONCLUSIONS: The positive association between γ-tocopherol and mortality suggests a potential physiological role for γ-tocopherol in response to pathological conditions.

Prediagnostic plasma polyunsaturated fatty acids and the risk of amyotrophic lateral sclerosis.

OBJECTIVE: To examine the association between prediagnostic plasma polyunsaturated fatty acids levels (PUFA) and amyotrophic lateral sclerosis (ALS). METHODS: We identified 275 individuals who developed ALS while enrolled in 5 US prospective cohorts, and randomly selected 2 controls, alive at the time of the case diagnosis, matched on cohort, birth year, sex, ethnicity, fasting status, and time of blood draw. We measured PUFA, expressed as percentages of total fatty acids, using gas liquid chromatography and used conditional logistic regression to estimate risk ratios (RR) and 95% confidence intervals (CI) for the association between PUFA and ALS. RESULTS: There was no association between total, n-3, and n-6 PUFA, eicosapentaenoic acid, or docosapentaenoic acid levels and ALS. Higher plasma α-linolenic acid (ALA) in men was associated with lower risk of ALS in age- and matching factor-adjusted analyses (top vs bottom quartile: RR = 0.21 [95% CI 0.07, 0.58], p for trend = 0.004). In women, higher plasma arachidonic acid was associated with higher risk (top vs bottom quartile: RR = 1.65 [95% CI 0.99, 2.76], p for trend = 0.052). Multivariable adjustment, including correlated PUFA, did not change the findings for ALA and arachidonic acid. In men and women combined, higher plasma docosahexaenoic acid (DHA) was associated with higher risk of ALS (top vs bottom quartile: RR = 1.56 [95% CI 1.01, 2.41], p for trend = 0.054), but in multivariable models the association was only evident in men. CONCLUSIONS: The majority of individual PUFAs were not associated with ALS. In men, ALA was inversely and DHA was positively related to risk of ALS, while in women arachidonic acid was positively related. These findings warrant confirmation in future studies.

Ratios of Food Amounts across Three Portion Size Categories on a Food Frequency Questionnaire in Men and Women.

BACKGROUND: For some quantitative food frequency questionnaire (QFFQ) items, data may be insufficient to set gram weights for multiple portion size (PS) categories. Ratios of food amounts across PS categories may be used to quantify these PS for less frequently consumed food items. OBJECTIVE: To explore the ratios of food amounts reported in 24-hour dietary recalls (24HDRs) by a sample of participants in a cohort study who chose the A (smallest) or C (largest) PS category on the QFFQ, relative to the food amounts for those who chose the B PS category. DESIGN: This study was conducted as a cross-sectional design. PARTICIPANTS/SETTING: Data were from participants (n=2,360) who completed three 24HDRs and the QFFQ in a calibration study of the Multiethnic Cohort Study in 1994-1997. MAIN OUTCOME MEASURES: Median food amounts were calculated from 24HDRs for participants who selected each PS category (A, smallest; B; and C, largest) of items on the QFFQ. A-to-B and C-to-B ratios were computed if reported by five or more people in the 24HDRs: A-to-B ratios for 68 items (men) and 88 items (women); C-to-B ratios for 93 items (men) and 79 items (women). STATISTICAL ANALYSES PERFORMED: The t test was used to compare the mean A-to-B ratios and C-to-B ratios as preset on the QFFQ with those from the 24HDRs and to examine sex differences. Analysis of variance was used to compare the mean ratios among race and ethnicity groups. RESULTS: Mean A-to-B and C-to-B ratios were 0.71±0.15 and 1.45±0.35 in men and 0.71±0.15 and 1.44±0.40 in women based on the 24HDRs. Compared with the original QFFQ PS (A-to-B ratio=0.5±0.07; C-to-B ratio=1.8±0.30), the ratios were closer to 1 both in men and women (P<0.001). There were no significant sex differences or racial or ethnic differences. CONCLUSIONS: These results provide guidance on appropriate ratios to use to set values for small and large PS categories on a QFFQ, particularly for items with insufficient information on usual PS.

Considering Gender Differences in Portion Sizes to Improve the Accuracy of Nutrient Intakes from A Food Frequency Questionnaire.

The aim of this study was to examine whether using gender specific-portion size (GS-PS) improves the accuracy of nutrient intake assessment by a quantitative food frequency questionnaire (QFFQ). For GS-PS quantification, a gram amount was assigned to each PS category for each food item for men and women separately using data from three 24 h dietary recalls (24HDRs) in a calibration study of the Multiethnic Cohort (men = 1141, women = 1150). Nutrient intakes were calculated from the QFFQ using the original-PS and the GS-PS, and were compared with 24HDRs. When intakes of energy and 15 nutrients were compared, absolute intakes calculated using the GS-PS were closer to intake levels of 24HDRs in both men and women. Using GS-PS did not affect intakes expressed as nutrient density or correlations between 24HDRs and the QFFQ. The current findings indicate that considering gender in PS determination can increase the accuracy of intake assessment by QFFQ for absolute nutrient intakes, but not for nutrient densities.

Prediagnostic plasma metabolomics and the risk of amyotrophic lateral sclerosis.

OBJECTIVE: To identify prediagnostic plasma metabolomic biomarkers associated with amyotrophic lateral sclerosis (ALS). METHODS: We conducted a global metabolomic study using a nested case-control study design within 5 prospective cohorts and identified 275 individuals who developed ALS during follow-up. We profiled plasma metabolites using liquid chromatography-mass spectrometry and identified 404 known metabolites. We used conditional logistic regression to evaluate the associations between metabolites and ALS risk. Further, we used machine learning analyses to determine whether the prediagnostic metabolomic profile could discriminate ALS cases from controls. RESULTS: A total of 31 out of 404 identified metabolites were associated with ALS risk (p < 0.05). We observed inverse associations (n = 27) with plasma levels of diacylglycerides and triacylglycerides, urate, purine nucleosides, and some organic acids and derivatives, while we found positive associations for a cholesteryl ester, 2 phosphatidylcholines, and a sphingomyelin. The number of significant associations increased to 67 (63 inverse) in analyses restricted to cases with blood samples collected within 5 years of onset. None of these associations remained significant after multiple comparison adjustment. Further, we were not able to reliably distinguish individuals who became cases from controls based on their metabolomic profile using partial least squares discriminant analysis, elastic net regression, random forest, support vector machine, or weighted correlation network analyses. CONCLUSIONS: Although the metabolomic profile in blood samples collected years before ALS diagnosis did not reliably separate presymptomatic ALS cases from controls, our results suggest that ALS is preceded by a broad, but poorly defined, metabolic dysregulation years before the disease onset.

Intake of cocoa products and risk of type-2 diabetes: the multiethnic cohort.

BACKGROUND/OBJECTIVES: As cocoa products may be protective against chronic disease due to their polyphenol content, the current study determined the association of chocolate consumption and flavanol intake with type-2 diabetes (T2D) incidence in the Multiethnic Cohort (MEC) Study. SUBJECTS/METHODS: The analysis included 151,691 participants of Native Hawaiian, Japanese American, Latino, African American, and white ancestry with 8487 incident T2D cases after 7.8 ± 3.5 years of follow-up. T2D status was based on three self-reports and confirmed by at least one of three administrative data sources. Dietary intake was assessed using a validated quantitative food frequency questionnaire, and flavanols from cocoa products were estimated from self-reported consumption of chocolate candy and drinks. Cox hazard regression, adjusted for potential confounders was applied to estimate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: For chocolate candy, both the highest vs. lowest (≥10 vs. <1 g/day) consumption (HR = 0.90; 95% CI, 0.83-0.97; ptrend = 0.01) and the frequency (≥4/week vs. <1/month) of intake (HR = 0.81; 95% CI, 0.72-0.91; ptrend = 0.0002) were inversely associated with T2D. The estimated flavanol intake from cocoa products (≥3 vs. <1 mg/day) also showed an inverse association with T2D risk (HR = 0.93; 95% CI, 0.88-0.99; ptrend = 0.02). Significant interaction terms indicated that the inverse relation was limited to Japanese Americans, normal-weight individuals, and to those without comorbidities. CONCLUSIONS: The current study confirms previous reports that participants with high intake of chocolate products and cocoa-derived flavanols experience a reduced risk of developing T2D even after controlling for sugar intake, diet quality, and other aspects of the diet.

Prediagnostic plasma branched-chain amino acids and the risk of amyotrophic lateral sclerosis.

OBJECTIVE: To assess whether prediagnostic levels of plasma branched-chain amino acids (BCAAs) are associated with amyotrophic lateral sclerosis (ALS) risk. METHODS: We included participants from 5 large cohort studies-The Nurses' Health Study, the Health Professionals Follow-up Study, the Cancer Prevention Study II Nutrition, the Multiethnic Cohort Study, and the Women's Health Initiative-and identified 275 individuals who developed ALS during follow-up. Two controls were randomly selected for each case, matched on cohort, age, sex, fasting status, and time of blood draw. We measured metabolites using liquid chromatography-mass spectrometry and used conditional logistic regression to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for the association of individual BCAAs with ALS risk. RESULTS: None of the 3 BCAAs was associated with a higher ALS risk. The risk estimates were similar for leucine (RR top vs bottom quartile: 0.87, 95% CI 0.57-1.33), isoleucine (RR top vs bottom quartile: 0.81, 95% CI 0.52-1.24), and valine (RR top vs bottom quartile: 0.80, 95% CI 0.52-1.23) in a multivariable analysis adjusted for body mass index, smoking, level of education, and physical activity. The estimates did not vary significantly by sex, fasting status, or time interval between blood draw and disease onset. CONCLUSION: The results from this study do not support the hypothesis that BCAAs are risk factors for ALS.

Diet quality measured by four a priori-defined diet quality indices is associated with lipid-soluble micronutrients in the Multiethnic Cohort Study (MEC).

BACKGROUND/OBJECTIVES: This study examined the long-term relation of lipid-soluble micronutrients with diet quality as assessed by four a priori-defined dietary patterns. SUBJECTS/METHODS: In a prospective design, nutritional biomarkers (carotenoids, tocopherols, retinol, and coenzyme Q10) were measured using a validated HPLC-based assay. General linear models were applied to obtain covariate-adjusted means of biomarkers for tertiles of four a priori diet quality indices: Healthy Eating Index (HEI) 2010, Alternative HEI (AHEI) 2010, Alternate Mediterranean Diet Score (aMED), and Dietary Approaches to Stop Hypertension (DASH). For a subcohort of 8367 participants within the Multiethnic Cohort (MEC), diet was assessed by a validated quantitative food frequency questionnaire in 1993-96 and serum was collected in 2001-06. RESULTS: Participants with the highest diet-quality scores had significantly higher serum concentrations of all carotenoids, total tocopherols, and α-tocopherol, whereas γ-tocopherol was inversely associated with diet quality. Adjusted means for the lowest vs. highest tertile of HEI 2010 were 1.2 vs. 1.5 mg/L for total carotenoids, 11.4 vs. 12.3 mg/L for total tocopherols, and 1.9 vs. 1.6 mg/L for γ-tocopherol (ptrend < 0.0001). The associations for the other dietary indices were similar; no indication for sex and ethnic differences was detected. Vegetable and fruit components were major predictors of most circulating micronutrients, but most other components were also associated. CONCLUSIONS: Higher diet-quality scores measured by four a priori diet quality indices were significantly associated higher serum concentrations of carotenoids and α-tocopherol, whereas γ-tocopherol was inversely associated with diet quality.

Methylation of imprinted IGF2 regions is associated with total, visceral, and hepatic adiposity in postmenopausal women.

Excess body fat, especially intra-abdominal fat, is a leading risk factor for metabolic diseases. Differentially methylated regions (DMRs) of two imprinted genes, insulin-like growth factor 2 (IGF2) and H19, have been associated with obesity due to their important roles in regulating body composition, but have not been examined in relation to intra-abdominal fat depots. Total body fat from whole-body dual energy X-ray absorptiometry and visceral and liver fat contents from abdominal magnetic resonance imaging in 48 healthy women aged 60-65 years (of White or Japanese ancestry) were each regressed on circulating leukocyte DNA methylation levels of IGF2 (at DMR0, DMR2a, and DMR2b) and H19 (at CTCF3) as assessed by pyrosequencing, while adjusting for age and race/ethnicity. Total fat mass was inversely associated with methylation levels of IGF2 DMR2b (P = 0.016). Total fat-adjusted visceral fat area (P = 0.062) and percent visceral fat measured at L4-L5 (P = 0.045) were associated with higher methylation levels of IGF2 DMR2b. Both total fat-adjusted percent liver fat (P = 0.039) and the presence of fatty liver (P = 0.015) were positively associated with IGF2 DMR2a methylation. Methylation levels of H19 CTCF3 were not associated with overall or intra/abdominal adiposity. The findings indicate that methylation levels of IGF2 DMR regions in leukocytes are associated with total body fat and with fat distribution in the viscera and liver independently of total adiposity.

Low Free Testosterone and Prostate Cancer Risk: A Collaborative Analysis of 20 Prospective Studies.

BACKGROUND: Experimental and clinical evidence implicates testosterone in the aetiology of prostate cancer. Variation across the normal range of circulating free testosterone concentrations may not lead to changes in prostate biology, unless circulating concentrations are low. This may also apply to prostate cancer risk, but this has not been investigated in an epidemiological setting. OBJECTIVE: To examine whether men with low concentrations of circulating free testosterone have a reduced risk of prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: Analysis of individual participant data from 20 prospective studies including 6933 prostate cancer cases, diagnosed on average 6.8 yr after blood collection, and 12 088 controls in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) of incident overall prostate cancer and subtypes by stage and grade, using conditional logistic regression, based on study-specific tenths of calculated free testosterone concentration. RESULTS AND LIMITATIONS: Men in the lowest tenth of free testosterone concentration had a lower risk of overall prostate cancer (OR=0.77, 95% confidence interval [CI] 0.69-0.86; p<0.001) compared with men with higher concentrations (2nd-10th tenths of the distribution). Heterogeneity was present by tumour grade (phet=0.01), with a lower risk of low-grade disease (OR=0.76, 95% CI 0.67-0.88) and a nonsignificantly higher risk of high-grade disease (OR=1.56, 95% CI 0.95-2.57). There was no evidence of heterogeneity by tumour stage. The observational design is a limitation. CONCLUSIONS: Men with low circulating free testosterone may have a lower risk of overall prostate cancer; this may be due to a direct biological effect, or detection bias. Further research is needed to explore the apparent differential association by tumour grade. PATIENT SUMMARY: In this study, we looked at circulating testosterone levels and risk of developing prostate cancer, finding that men with low testosterone had a lower risk of prostate cancer.

Portion Sizes from 24-Hour Dietary Recalls Differed by Sex among Those Who Selected the Same Portion Size Category on a Food Frequency Questionnaire.

BACKGROUND: Accounting for sex differences in food portions may improve dietary measurement; however, this factor has not been well examined. OBJECTIVE: The aim of this study was to examine sex differences in reported food portions from 24-hour dietary recalls (24HDRs) among those who selected the same portion size category on a quantitative food frequency questionnaire (QFFQ). DESIGN: This study was conducted with a cross-sectional design. PARTICIPANTS/SETTING: Participants (n=319) were members of the Hawaii-Los Angeles Multiethnic Cohort who completed three 24HDRs and a QFFQ in a calibration study conducted in 2010 and 2011. MAIN OUTCOME MEASURES: Portions of individual foods reported from 24HDRs served as the outcome measures. STATISTICAL ANALYSES PERFORMED: Mean food portions from 24HDRs were compared between men and women who reported the same portion size on the QFFQ, after adjustment for race/ethnicity using a linear regression model. Actual amount and the assigned amount of the selected portion size in the QFFQ were compared using one-sample t test for men and women separately. RESULTS: Of 163 food items with portion size options listed in the QFFQ, 32 were reported in 24HDRs by ≥20 men and ≥20 women who selected the same portion size in the QFFQ. Although they chose the same portion size on the QFFQ, mean intake amounts from 24HDRs were significantly higher for men than for women for "beef/lamb/veal," "white rice," "brown/wild rice," "lettuce/tossed salad," "eggs cooked/raw," "whole wheat/rye bread," "buns/rolls," and "mayonnaise in sandwiches." For men, mean portions of 14 items from the 24HDRs were significantly different from the assigned amounts for QFFQ items (seven higher and seven lower), whereas for women, mean portions of 14 items were significantly lower from the assigned amounts (with five significantly higher). CONCLUSIONS: These sex differences in reported 24HDR food portions-even among participants who selected the same portion size on the QFFQ-suggest that the use of methods that account for differences in the portions consumed by men and women when QFFQs are quantified may provide more accurate absolute dietary intakes.

Self-reported dietary flavonoid intake and serum markers of inflammation: the multiethnic cohort.

PURPOSE: To examine if dietary intake of foods rich in flavonoids, which have been shown to be inversely associated with chronic diseases, is associated with inflammatory processes. METHODS: This analysis includes controls of case-control studies nested within the Multiethnic Cohort (MEC) who completed a validated food frequency questionnaire at cohort entry. Biomarkers were assessed in blood donated during follow-up (mean = 9.6 years). We used multivariate linear regression adjusted for potential confounders to estimate associations between intake of flavanones, flavonols, and isoflavones and levels of adiponectin, leptin, C-reactive protein, interleukin (IL)-1ß, IL-6, IL-10, and tumor necrosis factor-α. RESULTS: Among the 1,287 participants, the respective median intakes of flavanones, flavonols, and isoflavones were 26.5, 12.4, and 1.3 mg/day at cohort entry. With the exception of flavanone intake, which was statistically significantly inversely associated with adiponectin (p = 0.01) and IL-6 concentrations (p = 0.01), none of the examined flavonoids was related with levels of adipokines or inflammatory markers. Heterogeneity by ethnicity was only observed for flavonol intake and IL-10 (pinteraction = 0.04) and may be the result of multiple testing. These null findings were confirmed in a subset of participants who completed a second dietary history within 2.6 years of blood draw. CONCLUSION: The current results do not support a consistent association between dietary intake of flavonoids and markers of inflammatory processes.

Sleep duration and incidence of type 2 diabetes: the Multiethnic Cohort.

OBJECTIVES: As an emerging risk factor for the rising incidence of type 2 diabetes, we examined sleep duration in relation to type 2 diabetes and several biomarkers. DESIGN: Prospective cohort recruited 1993-1996. SETTING: The Multiethnic Cohort in Hawaii and California. PARTICIPANTS: A cohort of 151,691 White, African American, Japanese American, Native Hawaiian, and Latino participants; 9695 cohort members had biomarker measurements. MEASUREMENTS: Sleep duration was self-reported at cohort entry. Diabetes status was obtained from 3 questionnaires and confirmed by 3 administrative data sources. Biomarkers were measured by standard assays 9.6±2.1 years after cohort entry. We estimated diabetes risk as a time-varying outcome using Cox regression adjusted for body mass index assessed at 3 time points and other known confounders and computed adjusted means of biomarkers by sleep hours. RESULTS: During 7.9±3.5 years of follow-up, 8487 new diabetes cases were diagnosed. Long sleep duration (≥9 hours), as compared with 7-8 hours, was significantly associated with higher incidence (hazard ratio, 1.12; 95% confidence interval 1.04-1.21), but the 4% elevated incidence for short sleep duration (≤6 hours) did not reach significance (95% confidence interval 0.99-1.09). After stratification, the associations appeared stronger in Japanese American than other ethnic groups and in participants without comorbidity. Hours of sleep were positively associated with C-reactive protein and triglycerides and inversely related to high-density lipoprotein cholesterol and adiponectin but not with leptin levels and homeostatic model assessment of insulin resistance. CONCLUSION: In this multiethnic population, the 12% higher diabetes risk for long sleep hours may be mediated through inflammation, a poor lipid profile, and lower adiponectin levels.

Pre-diagnostic plasma urate and the risk of amyotrophic lateral sclerosis.

OBJECTIVE: To prospectively examine for the first time the association between plasma urate levels measured in healthy participants and future amyotrophic lateral sclerosis (ALS) risk. METHODS: A pooled case-control study nested in five US prospective cohorts comprising 319,617 participants who provided blood, of which 275 had ALS during follow-up. Pre-diagnostic plasma urate was determined for all participants using a clinical colorimetric enzyme assay. Gender-specific multivariable-adjusted rate ratios (RR) of ALS incidence or death estimated by conditional logistic regression and pooled using inverse-variance weighting. RESULTS: In age- and matching factor-adjusted analyses, a 1 mg/dL increase in urate concentration was associated with RR = 0.88 (95% CI: [0.78, 0.997] p = 0.044). After adjustment for BMI, a strong predictor of ALS and urate levels, and other potential covariates, the RR = 0.89 (95% CI: [0.78, 1.02]; p = 0.08 for 1mg/dL increase in urate). CONCLUSION: Elevation of plasma urate was modestly inversely associated with the risk of ALS and warrants further study for a potential role in this disease.

Characterizing the neighborhood obesogenic environment in the Multiethnic Cohort: a multi-level infrastructure for cancer health disparities research.

PURPOSE: We characterized the neighborhood obesogenic environment in the Multiethnic Cohort (MEC) by examining the associations of obesity with attributes of the social and built environment, establishing a multi-level infrastructure for future cancer research. METHODS: For 102,906 African American, Japanese American, Latino, and white MEC participants residing predominately in Los Angeles County, baseline residential addresses (1993-1996) were linked to census and geospatial data, capturing neighborhood socioeconomic status (nSES), population density, commuting, food outlets, amenities, walkability, and traffic density. We examined neighborhood attributes and obesity (body mass index ≥ 30 kg/m2) associations using multinomial logistic regression, adjusting for individual-level (e.g., demographics, physical activity, and diet) and neighborhood-level factors. RESULTS: NSES was associated with obesity among African Americans, Latinos, and whites (p-trend ≤ 0.02), with twofold higher odds (adjusted odds ratios, 95% confidence intervals) for living in the lowest versus highest quintile among African American women (2.07, 1.62-2.65), white men (2.11, 1.29-3.44), and white women (2.50, 1.73-3.61). Lower density of businesses among African American and white women and lower traffic density among white men were also associated with obesity (p-trends ≤ 0.02). CONCLUSIONS: Our study highlights differential impacts of neighborhood factors across racial/ethnic groups and establishes the foundation for multi-level studies of the neighborhood context and obesity-related cancers.

Circulating sex hormones in relation to anthropometric, sociodemographic and behavioural factors in an international dataset of 12,300 men.

INTRODUCTION: Sex hormones have been implicated in the etiology of a number of diseases. To better understand disease etiology and the mechanisms of disease-risk factor associations, this analysis aimed to investigate the associations of anthropometric, sociodemographic and behavioural factors with a range of circulating sex hormones and sex hormone-binding globulin. METHODS: Statistical analyses of individual participant data from 12,330 male controls aged 25-85 years from 25 studies involved in the Endogenous Hormones Nutritional Biomarkers and Prostate Cancer Collaborative Group. Analysis of variance was used to estimate geometric means adjusted for study and relevant covariates. RESULTS: Older age was associated with higher concentrations of sex hormone-binding globulin and dihydrotestosterone and lower concentrations of dehydroepiandrosterone sulfate, free testosterone, androstenedione, androstanediol glucuronide and free estradiol. Higher body mass index was associated with higher concentrations of free estradiol, androstanediol glucuronide, estradiol and estrone and lower concentrations of dihydrotestosterone, testosterone, sex hormone-binding globulin, free testosterone, androstenedione and dehydroepiandrosterone sulfate. Taller height was associated with lower concentrations of androstenedione, testosterone, free testosterone and sex hormone-binding globulin and higher concentrations of androstanediol glucuronide. Current smoking was associated with higher concentrations of androstenedione, sex hormone-binding globulin and testosterone. Alcohol consumption was associated with higher concentrations of dehydroepiandrosterone sulfate, androstenedione and androstanediol glucuronide. East Asians had lower concentrations of androstanediol glucuronide and African Americans had higher concentrations of estrogens. Education and marital status were modestly associated with a small number of hormones. CONCLUSION: Circulating sex hormones in men are strongly associated with age and body mass index, and to a lesser extent with smoking status and alcohol consumption.