Cumulative Average Intake Research Articles

Intakes of Folate, Vitamin B6, and Vitamin B12 in Relation to Diabetes Incidence Among American Young Adults: A 30-Year Follow-up Study.

To prospectively examine intakes of folate, vitamin B6, and vitamin B12 in relation to diabetes incidence in a large U.S. cohort. A total of 4,704 American adults aged 18-30 years and without diabetes were enrolled in 1985-1986 and monitored until 2015-2016 in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Dietary assessment was conducted by a validated dietary history questionnaire at baseline, in 1992-1993, and in 2005-2006. The cumulative average intakes of folate, vitamin B6, and vitamin B12 were used in the analyses. Incident diabetes was ascertained by plasma glucose levels, oral glucose tolerance tests, hemoglobin A1c concentrations, and/or antidiabetic medications. During 30 years (mean 20.5 ± 8.9) of follow-up, 655 incident cases of diabetes occurred. Intake of folate, but not vitamin B6 or vitamin B12, was inversely associated with diabetes incidence after adjustment for potential confounders. Compared with the lowest quintile of total folate intake, the multivariable-adjusted hazard ratios (95% CI) in quintiles 2-5 were 0.85 (0.67-1.08), 0.78 (0.60-1.02), 0.82 (0.62-1.09), and 0.70 (0.51-0.97; P trend = 0.02). Higher folate intake was also associated with lower plasma homocysteine (P trend < 0.01) and insulin (P trend < 0.01). Among supplement users, folate intake was inversely associated with serum C-reactive protein levels (P trend < 0.01). Intake of folate in young adulthood was inversely associated with diabetes incidence in midlife among Americans. The observed association may be partially explained by mechanisms related to homocysteine level, insulin sensitivity, and systemic inflammation.

Associations between daily alcohol consumption and systemic lupus erythematosus-related cytokines and chemokines among US female nurses without SLE.

Moderate alcohol consumption has been associated with decreased systemic lupus erythematosus risk, but the biologic basis for this association is unknown. We aimed to determine whether moderate alcohol consumption was associated with lower concentrations of systemic lupus erythematosus-associated chemokines/cytokines in an ongoing cohort of female nurses without systemic lupus erythematosus, and whether the association was modified by the presence of systemic lupus erythematosus-related autoantibodies. About 25% of participants from the Nurses' Health Study (n = 121,700 women) and Nurses' Health Study 2 (n = 116,429) donated a blood sample; of these, 1177 women were without systemic lupus erythematosus at time of donation. Cumulative average and current (within 4 years) intakes of beer, wine or liquor were assessed from pre-blood draw questionnaires. Chemokine/cytokine concentrations (stem cell factor, B-lymphocyte stimulator, interferon-inducible protein-10, interferon-alpha, interleukin-10) and antibodies against dsDNA and extractable nuclear antigens were obtained using enzyme-linked immunosorbent assays. Antinuclear antibodies were detected by indirect immunofluorescence on HEp-2 cells. At blood draw, the women's mean age was 56 years and 22% were antinuclear antibody positive; 36% were African-American. About half (46%) reported consuming 0-5 g/day of alcohol. Stem cell factor levels were 0.5% lower (p < 0.0001) for every gram per day increase in cumulative average alcohol consumption. Women who consumed >5 g/day had mean stem cell factor levels 7% lower (p = 0.002) than non-drinkers. Other cytokines were not significantly associated with alcohol intake. Autoantibody status did not modify observed associations. In this study of female nurses, moderate alcohol consumption was associated with lower stem cell factor levels, suggesting a plausible mechanism through which alcohol may lower systemic lupus erythematosus risk might be by decreasing circulating stem cell factor.

Intake of Furocoumarins and Risk of Skin Cancer in 2 Prospective US Cohort Studies

In prior studies, higher citrus consumption was associated with higher risk of cutaneous malignant melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC). Furocoumarins, compounds with phototoxicity and photocarcinogenicity in citrus, may be responsible for the association. The objective of the study was to investigate the association between furocoumarin intake and skin cancer risk. A total of 47,453 men from the Health Professionals Follow-Up Study (HPFS) and 75,291 women from the Nurses' Health Study (NHS) with diet data collected every 2-4 y in the 2 prospective cohort studies were included. A furocoumarin food composition database for 7 common furocoumarins [bergaptol, psoralen, 8-methoxypsoralen, bergapten, 6',7'-dihydroxybergamottin (6'7'-DHB), epoxybergamottin, and bergamottin] was developed and used to calculate participants' cumulative average and energy-adjusted furocoumarin intake. Multivariate HRs and 95% CIs of the associations between furocoumarin intake and skin cancer risk were estimated using Cox proportional hazards models. Analyses were performed separately in each cohort as well as pooled using a fixed-effects model. Throughout follow-up (1984-2012 in the NHS and 1986-2012 in the HPFS), we identified 1593 melanoma, 4066 SCC, and 28,630 BCC cases. Higher intake of total furocoumarins was associated with an increased risk of BCC; the pooled HR comparing the top with the bottom quintile was 1.16 (95% CI: 1.11, 1.21; P-trend=0.002). Higher intakes of bergaptol, bergapten, 6'7'-DHB, and bergamottin were also significantly associated with increased BCC risk. No significant associations were found between intake of total furocoumarins and the risks of SCC or melanoma. Intakes of total furocoumarins as well as some individual furocoumarins were associated with an increased risk of skin cancer, especially BCC, in 2 cohorts of US health professionals.

Magnesium Intake Is Inversely Associated with the Risk of Non-Alcoholic Fatty Liver Disease Among American Young adults

Abstract Objectives To examine magnesium (Mg) intake from diet and supplements during young adulthood in relation to risk of non-alcoholic fatty liver disease (NAFLD) in midlife. Methods A total of 2712 black and white American adults aged 18 to 30 years were recruited in the Coronary Artery Risk Development in Young Adult (CARDIA) study in 1985–1986 (baseline) with 8 additional examinations during 25 years thereafter. Mg intake was assessed at baseline and exam years 7 and 20 using the CARDIA diet history questionnaires. Computed tomography (CT) scanning was performed at exam year 25 (2010–2011) to ascertain NAFLD cases, which was defined as liver attenuation (LA) ≤51 Hounsfield units after exclusion for other causes of liver fat. Logistic regression was used to examine the association between cumulative average Mg intake and the risk of NAFLD. Results At exam year 25, 638 NAFLD cases were documented. An inverse association between total Mg intake (from diet and supplements) and NAFLD risk was observed after adjustment sociodemographics, major lifestyle factors, dietary quality, and clinical measurements (body mass index, blood pressure, lipid profiles, and fasting insulin). Compared with participants in the lowest quintile of Mg intake, those in the highest quintile had a 54% lower risk of NAFLD [multivariable-adjusted odds ratio = 0.46, 95% confidence interval = (0.25, 0.87), P for trend = 0.0498]. Consistently, there was an inverse association between whole grain consumption (a major food source of magnesium) and NAFLD risk. Conclusions This study suggests that higher intake of Mg throughout adulthood is associated with a lower risk of NAFLD in middle age. Funding Sources The Coronary Artery Risk Development in Young Adults Study is supported by grants from the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham, Northwestern University, University of Minnesota, and Kaiser Foundation Research Institute.This study is also partially supported by the NIH grants and NHLBI.

Dietary iodine, seaweed consumption, and incidence risk of metabolic syndrome among postmenopausal women: a prospective analysis of the Korean Multi-Rural Communities Cohort Study (MRCohort).

Despite a beneficial role of iodine and seaweed consumption against metabolic syndrome (MetS), which is high in postmenopausal women, few studies investigated such associations in a prospective study.This study aimed to investigate the association of dietary iodine and seaweed consumption with the incidence of MetS and its components in postmenopausal women. A total of 2588 postmenopausal women aged ≥ 40years were recruited between 2005 and 2011 in the Multi-Rural Communities Cohort (MRCohort). A validated semiquantitative food frequency questionnaire was used to collect dietary intake data. MetS was defined as three of five components [abdominal obesity, elevated blood pressure, glucose, triglyceride, and low-high density lipoprotein cholesterol (HDL-C)] and the incidence of MetS was checked every 2-4years. The incidence rate ratio (IRR) was estimated using a modified Poisson regression model with a robust error estimator. During the mean follow-up period (3.4 ± 2.1years), MetS occurred in 481 participants. The median cumulative average iodine intake was 108.9µg/day (interquartile range, 60.8-190.2µg/day). In multivariable analyses, average iodine and seaweed consumption were inversely associated with MetS (IRR = 0.61, 95% CI 0.47-0.78 in the highest quartile of iodine intake, P for trend = 0.0018; IRR = 0.52, 95% CI 0.39-0.69 in the highest quartile of seaweed consumption, P for trend = 0.0004). Among MetS components, blood glucose (> 100mg/dL), blood pressure (≥ 130/85mmHg), and lipid profiles (triglyceride, ≥ 150mg/dL and HDL-C, < 50mg/dL) were significantly inversely associated with dietary iodine and seaweed consumption, but there was no clear association for waist circumference (≥ 85cm). Dietary iodine and seaweed consumption may be inversely associated with MetS incidence and its individual abnormalities in postmenopausal women.

Adult dietary fat intake and ovarian cancer risk

The association of dietary fat intake with ovarian cancer risk has been inconsistent across populations. We examined dietary fat intake, overall and by type and ovarian cancer risk in two prospective cohort studies. We assessed long-term dietary fat intake among Nurses' Health Study (NHS) and NHSII participants using food frequency questionnaires administered every 2-4 years beginning in 1984 and 1991, respectively. We examined cumulative energy-adjusted intake of total fat, specific types of fat (animal, vegetable, saturated, monounsaturated, polyunsaturated and trans fat) and cholesterol. We identified 700 ovarian cancer cases in NHS and 196 in NHSII with dietary information. Cox proportional hazards regression was used to estimate associations between intake and ovarian cancer risk. Dietary fat intake changed over time in both cohorts and was lower in NHS than NHSII. Higher cumulative average intakes of animal fat and cholesterol were significantly positively associated with risk of ovarian cancer in NHS (relative risk [RR] comparing extreme quartiles = 1.57, 95% CI: 1.20, 2.06 and 1.35, 95% CI: 1.08, 1.69, respectively), but not in NHSII. Other dietary fat sources were not clearly associated with risk in either population. We did not observe clear associations between dietary fat and ovarian cancer risk in two large prospective cohort studies.

Cumulative intake of artificially sweetened and sugar-sweetened beverages and risk of incident type 2 diabetes in young adults: the Coronary Artery Risk Development In Young Adults (CARDIA) Study

Epidemiological evidence has demonstrated a positive association between artificially sweetened beverage (ASB) and sugar-sweetened beverage (SSB) consumption and type 2 diabetes (T2D) risk. However, research informing this topic in young adults is limited. This study examined the association between ASB, SSB, and total sweetened beverage (TSB; combined ASB and SSB) consumption and T2D risk in young adults. A prospective analysis of 4719 Black and White men and women aged 18-30 y at baseline was conducted from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Each participant's beverage intake was assessed using the CARDIA Diet History at baseline and at study Years 7 and 20. Multivariable Cox proportional hazards regression models were used to examine cumulative average ASB, SSB, and TSB intakes and risk of T2D. During the 30-y follow-up period, 680 participants developed T2D. ASB consumption was associated with a 12% greater risk of T2D per serving/day (HR 1.12, 95% CI 1.04-1.20) in a model adjusted for lifestyle factors, diet quality, and dieting behavior. Further adjustments for baseline BMI (HR 1.07, 95% CI 0.99-1.14) and weight change during follow-up (HR 1.04, 95% CI 0.97-1.12) attenuated the association. SSB and TSB consumption as continuous variables per 1 serving/day of intake were associated with 6% and 5% increased risks of T2D, respectively (HRSSB 1.06, 95% CI 1.01-1.10; HRTSB 1.05, 95% CI 1.01-1.09), in the model accounting for lifestyle factors, dieting behavior, baseline BMI, and weight change. Results were consistent when the exposures were modeled in categories of consumption and quintiles. In young adults, long-term ASB, SSB, and TSB consumption were associated with increased risks of T2D. However, the estimates for ASB were attenuated when accounting for weight changes.

High Chili Intake and Cognitive Function among 4582 Adults: An Open Cohort Study over 15 Years.

We aimed to examine the association between chili intake and cognitive function in Chinese adults. This is a longitudinal study of 4852 adults (age 63.4 ± 7.7) attending the China Health and Nutrition Survey during 1991 and 2006. Cognitive function was assessed in 1997, 2000, 2004 and 2006. In total, 3302 completed cognitive screening tests in at least two surveys. Chili intake was assessed by a 3-day food record during home visits in each survey between 1991 and 2006. Multivariable mixed linear regression and logistic regression were used. Chili intake was inversely related to cognitive function. In fully adjusted models, including sociodemographic and lifestyle factors, compared with non-consumers, those whose cumulative average chili intake above 50 g/day had the regression coefficients (and 95% CI) for global cognitive function of −1.13 (−1.71–0.54). Compared with non-consumers, those with chili consumption above 50 g/day had the odds ratio (and 95% CI) of 2.12(1.63–2.77), 1.56(1.23–1.97) for self-reported poor memory and self-reported memory decline, respectively. The positive association between chili intake and cognitive decline was stronger among those with low BMI than those with high BMI. The longitudinal data indicate that higher chili intake is positively associated with cognitive decline in Chinese adults in both genders.

Association of High Intakes of Vitamins B6 and B12 From Food and Supplements With Risk of Hip Fracture Among Postmenopausal Women in the Nurses’ Health Study

Vitamin supplementation far exceeding recommended doses is popular in segments of the population. However, adverse effects can occur. In a previous secondary analysis of combined data from 2 double-blind randomized clinical trials (RCTs), an unexpected increased risk of hip fracture was found among those treated with high doses of vitamin B6 in combination with vitamin B12. To study if high intakes of vitamins B6 and B12 from food and supplements were associated with a risk of hip fracture in the Nurses' Health Study and to investigate whether combined high intakes of both vitamins conferred a particularly increased fracture risk. In this prospective cohort study, 75 864 postmenopausal women in the United States were followed up from June 1984 through May 2014. The dates of analysis were July 2016 to June 2018. Information on hip fracture and a wide range of potential confounders was collected at baseline and with biennial follow-up questionnaires. Extensive dietary information was collected approximately every 4 years with a semiquantitative food frequency questionnaire. Relative risks (RRs) were calculated by Cox proportional hazards regression, with cumulative average intakes of vitamins B6 and B12 as main exposures, adjusting for potential confounders. Hip fracture. During follow-up, 2304 of 75 864 women had a hip fracture. Among the women with hip fractures, the median (range) age at hip fracture was 75.8 (46.7-93.0) years and the mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) was 24.3 (4.6). Median (interquartile range) cumulative average intakes of total vitamins B6 and B12 were 3.6 (4.8) mg/d and 12.1 (11.7) μg/d, respectively. Both vitamin B6 (RR, 1.29; 95% CI, 1.04-1.59 for an intake of ≥35 vs <2 mg/d; P = .06 for linear trend) and vitamin B12 (RR, 1.25; 95% CI, 0.98-1.58 for an intake of ≥30 vs <5 μg/d; P = .02 for linear trend) were associated with increased fracture risk. Risk was highest in women with a combined high intake of both vitamins (B6 ≥35 mg/d and B12 ≥20 μg/d), exhibiting an almost 50% increased risk of hip fracture (RR, 1.47; 95% CI, 1.15-1.89) compared with women with a low intake of both vitamins (B6 <2 mg/d and B12 <10 μg/d). In this cohort study, a combined high intake of vitamins B6 and B12 was associated with an increased risk of hip fracture. The intakes were far higher than the recommended dietary allowances. These findings add to previous studies suggesting that vitamin supplements should be used cautiously because adverse effects can occur.

Abstract P1-09-01: CD8+ T-cell gene expression and signatures in breast cancer and adjacent normal breast tissue: Association with body mass index, alcohol intake, and age at diagnosis

Abstract Background: Our understanding of mediators of immune infiltration in breast cancer and normal breast tissue remains limited. We hypothesize that patient factors known to be associated with inflammation and immune subsets, including body mass index, alcohol intake, and age and diagnosis, may play an important role in the tumor-immune microenvironment. Analyses of immune gene expression and signatures facilitate interrogation of the immune microenvironment in large patient cohorts. Methods: Participants from the Nurses' Health Study cohorts I and II diagnosed with invasive breast cancer were included. Total RNA extracted and microarray performed for 882 tumor and 695 tumor-adjacent samples, of which 623 tumors have matched tumor-adjacent data. CD8+ T-cell expression metrics were assessed: CD8A single gene expression (CD8Agene), a CD8 T-cell signature (CD8sig), and a tumor infiltrating lymphocyte signature derived from the GeparSixto clinical trial (GSAct). Standard clinicopathologic features were evaluated, as well as body mass index (BMI) one year prior to diagnosis, cumulative average alcohol intake, and age at diagnosis. Results: Overall, tumor and adjacent normal tissue demonstrated positive correlation of CD8Agene, CD8sig, and GSAct (n=623 pairs, Pearson's r = 0.46, 0.36, 0.31, respectively; all p&amp;lt;0.001). Similar correlations were present in TCGA breast cancer, an independent cohort (n=112 pairs, Pearson's r = 0.34, 0.17, 0.45, respectively; all p&amp;lt;0.001). We evaluated paired tumor and adjacent normal samples within individual immunohistochemical (IHC) subtype or PAM50 subtype by Wilcoxon signed-rank test. There was not a consistent trend for CD8Agene, CD8sig, nor GSAct to be greater in tumor or normal within subtypes. We then evaluated patient features/exposures and tumor immune expression metrics. For tumor-adjacent normal, there was no significant association of alcohol intake, BMI, or age at diagnosis with CD8 gene/expression metrics. For tumor tissue, a multivariate model demonstrated that BMI one year before diagnosis was significantly associated with CD8Agene expression. There was no significant association of alcohol intake or age at diagnosis with CD8 gene/expression metrics. We are currently evaluating the association of these CD8 T-cell gene expression signatures with CD8 T-cell immunohistochemistry in a subset of patients, which will be reported at the time of abstract presentation. Conclusion: In this cohort of over 600 tumor:normal pairs and a separate validation cohort, multiple distinct CD8+ T-cell expression metrics are correlated between breast cancer and tumor-adjacent normal breast tissue. This suggests that the adjacent normal breast may reflect an altered immune microenvironment in the context of breast cancer. While age at diagnosis and alcohol intake are not significantly associated with tumor CD8 expression metrics, BMI was significantly associated with tumor CD8Agene expression in a multivariate model. Citation Format: Damicis A, Heng YJ, Kensler K, Asad S, Adams E, Singh J, Zhang Y, Nock W, Wesolowski R, Williams N, Reinbolt R, Sardesai S, VanDeusen J, Noonan A, Lustberg MB, Ramaswamy B, Eliassen AH, Hankinson SE, Tamimi R, Stover DG. CD8+ T-cell gene expression and signatures in breast cancer and adjacent normal breast tissue: Association with body mass index, alcohol intake, and age at diagnosis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-09-01.

Effects of seafood consumption and toenail mercury and selenium levels on cognitive function among American adults: 25 y of follow up.

The aim of this study was to examine the longitudinal association between seafood and intake of long-chain ω-3 polyunsaturated fatty acids (LCω-3 PUFA) and cognitive function and to explore the possible effect modifications owing to mercury (Hg) and selenium (Se) levels. Participants (N = 3231) from the CARDIA (Coronary Artery Risk Development in Young Adults) study underwent baseline examination and were reexamined in eight follow-up visits. Diet was assessed at baseline and in exam years 7 and 20. Toenail Hg and Se were measured at exam year 2. Cognitive function was measured at exam year 25 using three tests: Rey Auditory Verbal Learning Test (RAVLT), Digit Symbol Substitution Test (DSST), and the Stroop test. The general linear regression model was used to examine cumulative average intakes of LCω-3 PUFA and seafood in relation to the cognitive test scores; and to explore the possible effect modifications caused by Hg and Se. LCω-3 PUFA intake was significantly associated with better performance in the DSST test (quintile 5 versus quintile 1; mean difference = 1.74; 95% confidence interval, 0.19-3.29; Ptrend, 0.048]), but not in the RAVLT and Stroop tests. Similar results were observed for intakes of eicosapentaenoic acid, docosahexaenoic acid, and non-fried seafood. The observed associations were more pronounced in participants with body mass index ≥25 kg/m2, but not significantly modified by toenail Hg or Se. This longitudinal study supported the hypothesis that LCω-3 PUFA or non-fried seafood intake is associated with better cognitive performance in psychomotor speed among US adults, especially those who are overweight or obese.

Dietary Acrylamide Intake and Risk of Renal Cell Carcinoma in Two Large Prospective Cohorts.

Background: Accumulating evidence suggests that dietary acrylamide intake is not associated with the risk of most cancers in humans. However, a meta-analysis of five epidemiologic studies found a suggestion of an increased risk of kidney cancer with higher dietary acrylamide intake.Methods: We investigated this association in the prospective Health Professionals Follow-up Study (HPFS; 1986-2014) and Nurses' Health Study (NHS; 1980-2014) cohorts. Dietary acrylamide intake was calculated on the basis of 46 acrylamide-containing foods reported on food frequency questionnaires completed every 4 years. The associations with the incidence of total and fatal renal cell carcinoma (RCC; n = 292/84 HPFS, n = 337/87 NHS) during more than two decades of follow-up were assessed using Cox proportional hazards models adjusting for potential confounders.Results: There was no association between cumulative average or baseline acrylamide intake and the risk of total or fatal RCC risk in men or women. Acrylamide intake was also not associated with RCC risk among never-smokers, nor was it associated with the risk of clear cell RCC.Conclusions: Dietary acrylamide was not associated with risk of RCC in two long-term prospective cohorts with repeated measures of dietary intake.Impact: This analysis of RCC adds to the body of evidence that dietary acrylamide is not an important cancer risk factor in humans. Cancer Epidemiol Biomarkers Prev; 27(8); 979-82. ©2018 AACR.

Dietary acrylamide intake and risk of renal cell carcinoma in two large prospective cohorts.

677 Background: Acrylamide, which has been classified as a probable human carcinogen, is formed during the processing and cooking of many commonly consumed, carbohydrate-rich foods. Accumulating evidence suggests that dietary intake of acrylamide intake is not associated with the risk of most cancers in humans. A meta-analysis of five epidemiological studies, however, found a suggestion of an increased risk of kidney cancer with higher acrylamide intakes. We investigated this association in two large, prospective cohorts. Methods: Acrylamide intake was calculated from food frequency questionnaires completed every four years in the Nurses’ Health Study (NHS; 1980-2014; n = 88,770) and the Health Professionals Follow-up Study (HPFS; 1986-2014; n = 47,802). Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association with renal cell carcinoma (RCC), adjusting for known and suspected risk factors. Results: We documented 569 incident cases of RCC during follow-up, 337 in women and 232 in men. There was no association between cumulative average acrylamide intake and risk of RCC risk in women (HR for top versus bottom quartile of intake: 0.85; 95% CI: 0.62-1.18; p-value for linear trend across quartiles: 0.42) or men (HR: 1.09; 95% CI: 0.77-1.55; p-trend: 0.96). Baseline acrylamide intake was also unassociated with RCC risk. Acrylamide intake was not associated with risk of fatal RCC, risk among never-smokers, or risk of clear cell RCC. Intake of foods and food groups that are the major contributors to acrylamide intake – breads, baked goods, breakfast cereal, potatoes, and coffee – were likewise not associated with risk of total or fatal RCC in women or in men. Conclusions: Dietary acrylamide was not associated with the risk of RCC in two long-term, prospective cohorts of women and men with updated measures of dietary intakes. This analysis of renal cell carcinoma adds to the body of evidence that dietary acrylamide is not an important risk factor for cancer in humans.

Chilli intake is inversely associated with hypertension among adults

This study aimed to examine the association between chilli intake and the incidence of hypertension in a Chinese adult population. Adults aged 20-75 years in the China Health and Nutrition Survey were followed from 1991 to 2011. Dietary data were collected during home visits using a 3-day food record in 1991, 1993, 1997, 2000, 2004, 2006, 2009 and 2011. Cox regression was used in the analysis. Blood pressure was measured at each data collection point. 13,670 adults were followed for a median of 9.0 years. During 132,089 person years of follow-up 4040 subjects developed hypertension. Chilli consumption was inversely associated with the incidence of hypertension. The incidence rate of hypertension was 30.5, 33.4, 31.9, and 24.0 per 1000 person years among those who consumed no chilli or 1-20, 20.1-50, ≥50.1g/day respectively. Adjusting for age, gender, energy intake, sodium and fat intake, smoking, alcohol consumption and physical activity, those with increasing cumulative average chilli intake were less likely to develop hypertension: 0, 1-20, 20.1-50 and ≥50.1g/day had a hazard ratio (HR) for hypertension of 1.00, 0.80 (95%CI 0.73-0.88), 0.81 (0.73-0.89) and 0.65 (0.57-0.75) (p for trend <0.001) respectively. The association was independent of overall dietary patterns and BMI. There was no significant interaction between chilli intake and gender, income, education and residence (urban/rural) in relation to the risk of hypertension. Chilli intake is inversely associated with the risk of developing hypertension in Chinese adults.

No association between dietary sodium intake and the risk of multiple sclerosis.

To prospectively investigate the association between dietary sodium intake and multiple sclerosis (MS) risk. In this cohort study, we assessed dietary sodium intake by a validated food frequency questionnaire administered every 4 years to 80,920 nurses in the Nurses' Health Study (NHS) (1984-2002) and to 94,511 in the Nurses' Health Study II (NHSII) (1991-2007), and calibrated it using data from a validation study. There were 479 new MS cases during follow-up. We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the effect of energy-adjusted dietary sodium on MS risk, adjusting also for age, latitude of residence at age 15, ancestry, body mass index at age 18, supplemental vitamin D intake, cigarette smoking, and total energy intake in each cohort. The results in both cohorts were pooled using fixed effects models. Total dietary intake of sodium at baseline was not associated with MS risk (highest [medians: 3.2 g/d NHS; 3.5 g/d NHSII] vs lowest [medians: 2.5 g/d NHS; 2.8 g/d NHSII] quintile: HRpooled 0.98, 95% CI 0.74-1.30, p for trend = 0.75). Cumulative average sodium intake during follow-up was also not associated with MS risk (highest [medians: 3.3 g/d NHS; 3.4 g/d NHSII] vs lowest [medians: 2.7 g/d NHS; 2.8 g/d NHSII] quintile: HRpooled 1.02, 95% CI 0.76-1.37, p for trend = 0.76). Comparing more extreme sodium intake in deciles yielded similar results (p for trend = 0.95). Our findings suggest that higher dietary sodium intake does not increase the risk of developing MS.

Increased Yogurt Intake Lowers Risk of Cardiovascular Disease among Middle‐Aged Adults with High Blood Pressure

BackgroundHigh blood pressure (HBP) is a major risk factor for cardiovascular disease (CVD), the leading cause of mortality worldwide. Short‐term clinical trials have found beneficial effects of higher dairy intakes, especially yogurt, on CVD risk among those with HBP. However, long‐term studies are lacking.ObjectiveTo estimate the independent effects of total dairy and yogurt on risk of incident CVD among middle‐aged adults with HBP. Secondarily, possible effect modification by a healthy diet pattern was explored.MethodsSubjects included 57,768 30–55 year‐old women in the Nurses' Health Study (NHS) and 18,593 40–75 year‐old men in the Health Professionals Follow‐Up Study (HPFS) who reported HBP. Subjects with prevalent CVD, diabetes, or cancer were excluded. Cumulative average dairy intakes were derived from validated, semi‐quantitative food frequency questionnaires every 4 years. CVD, defined as myocardial infarction (MI) or stroke, was ascertained via self‐report with medical record review. NHS and HPFS subjects were followed for incident CVD for up to 30 and 24 years, respectively from the time of first reported HBP diagnosis. Time dependent Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) while controlling for age, race, family history of HBP or MI, BP medication use, smoking, alcohol, physical activity, BMI, and intakes of energy, fiber and trans fats. A DASH (Dietary Approaches to Stop Hypertension) diet score was calculated to explore effect modification by diet quality.ResultsThere were 5,468 total CVD cases in both cohorts, with 3,678 and 1,790 incident CVD cases in the NHS and HPFS, respectively. Of the 3,678 CVD cases in NHS, 1,887 were MI events and 1,791 strokes. In HPFS, there were 1,267 MI events and 523 incident strokes. Yogurt intake was inversely associated with risk of CVD among those with prevalent HBP (p for linear trend &lt;0.01 for both NHS and HPFS). Participants who consumed yogurt twice or more weekly in the NHS and HPFS had 17% (95% CI: 0.75–0.92) and 18% (95% CI: 0.68–0.97) reductions on risk of CVD, respectively. The effect of yogurt was further modified by a healthy diet pattern (as measured by a DASH score). Regular yogurt consumers in the NHS (≥2 servings/week) and HPFS (≥1 serving/week) with higher DASH scores (≥25 for both cohorts) had 19% (95% CI: 0.71–0.92) and 31% (95% CI: 0.57–0.83) lower risks of CVD, respectively. Total dairy intake was inversely associated with CVD risk among men. Finally, for participants in both NHS and HPFS whose diet more closely matched that of a DASH diet (DASH score ≥22), consuming ≥1 serving/day of dairy led to 12% (95% CI: 0.79–0.97) and 16% (95% CI: 0.73–0.97) lower risks of CVD, respectively.ConclusionHigher usual yogurt intakes were associated with lower risks of incident CVD in both women and men with prevalent HBP. Total dairy intake was particularly beneficial for men with HBP. When combined with a higher DASH score, higher total dairy and yogurt intakes led to meaningful reductions in CVD risk in both cohorts. These results suggest that incorporation of yogurt into a healthy diet pattern in hypertensive adults may provide a valuable non‐pharmacological approach to CVD prevention.Support or Funding InformationNational Dairy Council and the Boston Nutrition Obesity Research Center

Chilli consumption and the incidence of overweight and obesity in a Chinese adult population.

The frequency of spicy food intake has recently been associated with a reduced risk of mortality in the Chinese population. This study aimed to prospectively examine the association between chilli intake and the incidence of overweight/obesity in a Chinese adult population. Adults aged 20-75 years in the China Health and Nutrition Survey were followed between 1991 and 2011. Dietary data were collected during home visits using a 3-day food record in 1991, 1993, 1997, 2000, 2004, 2006, 2009 and 2011. Cox regression was used in the analysis. Overweight/obesity was defined as body mass index ⩾25 kg m-2. A total 12 970 adults were followed for a median of 9 years. During 126 884 person-years of follow-up, 3203 subjects developed overweight/obesity. The absolute incidence rate of overweight/obesity was 26.4, 22.3, 24.4 and 20.5 per 1000 person-years among those who consumed no chilli or 1-20, 20.1-50, ⩾50.1 g per day, respectively. Chilli consumption was therefore inversely associated with the incidence of overweight/obesity. After adjusting for age, gender, energy and fat intake, smoking, alcohol drinking and physical activity, those whose cumulative average chilli intake was 0, 1-20, 20.1-50 and ⩾50.1 g per day had a hazard ratio for overweight/obesity of 1.00, 0.81 (95% confidence interval=0.73-0.89), 0.77 (0.69-0.86) and 0.73 (0.63-0.84); P for trend <0.001, respectively. There was no interaction between chilli intake and gender, income, education and residence (urban/rural) in relation to the risk of overweight/obesity. Chilli intake is inversely associated with the risk of becoming overweight/obese in Chinese adults.

Influence of Alcohol Consumption on the Risk of Systemic Lupus Erythematosus Among Women in the Nurses' Health Study Cohorts.

Moderate alcohol consumption has antiinflammatory properties and is associated with reduced cardiovascular disease and rheumatoid arthritis risks. We investigated the association between alcohol consumption and systemic lupus erythematosus (SLE) risk among women followed in the Nurses' Health Study (NHS) cohorts. We conducted a prospective cohort analysis among 204,055 women in NHS (1980-2012) and NHSII (1989-2011) who were free of connective tissue disease and provided alcohol information at baseline. Alcohol consumption was assessed using a semiquantitative food frequency questionnaire every 2-4 years. We validated incident SLE through medical record review after self-report. Cox proportional hazards models estimated hazard ratios (HRs) for SLE based on cumulative average alcohol intake, adjusting for potential confounders. Results were meta-analyzed using DerSimonian and Laird random-effects models. We further investigated SLE risk associated with wine, beer, and liquor intake. We identified 125 incident SLE cases in NHS and 119 in NHSII. Mean ± SD age at SLE diagnosis was 55.8 ± 9.5 years in NHS and 43.4 ± 7.7 years in NHSII. Compared to no alcohol intake, the meta-analyzed multivariable HR for cumulative alcohol consumption ≥5 gm/day was 0.61 (95% confidence interval [95% CI] 0.41-0.89). When limiting alcohol exposure to >4 years prior to SLE diagnosis, the multivariable HR was similar: 0.61 (95% CI 0.41-0.91). Women who drank ≥2 servings/week of wine had significantly decreased SLE risk (HR 0.65, 95% CI 0.45-0.96) compared to women who did not drink wine. In these large prospective cohorts, we demonstrated an inverse association between moderate alcohol consumption (≥5 grams or 0.5 drink/day) and SLE risk in women.

Dietary Intakes of Eicosapentaenoic Acid and Docosahexaenoic Acid and Risk of Age-Related Macular Degeneration

To evaluate the associations between intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the intermediate and advanced stages of age-related macular degeneration (AMD). Prospective cohort study. We followed 75 889 women from the Nurses' Health Study and 38 961 men from the Health Professionals Follow-Up Study who were at least 50 years old, from 1984 to 2012 and 1986 to 2010, respectively. Cohort participants are mostly white (≥95%). We assessed dietary intake by a validated food frequency questionnaire (FFQ) at baseline and every 4 years. We calculated cumulative average intakes of EPA and DHA from FFQs and also computed predicted erythrocyte and plasma scores directly from food intake using regression models. Cox proportional hazards models were used to compute the associations with AMD outcomes. We confirmed 1589 incident intermediate and 1356 advanced AMD cases (primarily neovascular AMD) with a visual acuity of 20/30 or worse, owing primarily to AMD, by medical record review. For intermediate AMD, the pooled hazard ratio (HR) between the 2 cohorts for DHA comparing the extreme quintiles of intake was 0.78 (95% confidence interval [CI], 0.66-0.92; P trend, 0.008) and for EPA+ DHA was 0.83 (95% CI, 0.71-0.98; P trend, 0.03). The pooled HR for fatty fish, comparing ≥5 servings per week to almost never, was 0.61 (95% CI, 0.46-0.81; P trend, <0.001). For advanced AMD, the pooled HR for DHA was 1.01 (95% CI, 0.84-1.21; P trend, 0.75) and for fatty fish was 0.80 (95% CI, 0.59-1.08; P trend, 0.11). Secondary analyses using predicted erythrocyte and plasma scores of EPA and DHA yielded slightly stronger inverse associations for intermediate AMD and similar results for advanced AMD. Higher intakes of EPA and DHA may prevent or delay the occurrence of visually significant intermediate AMD. However, the totality of current evidence for EPA and DHA and advanced AMD is discordant, though there was no association with advanced AMD in the present study.

Abstract LB-380: Alcohol consumption and transcriptomic differences in breast tumor

Abstract Objective: Alcohol consumption is consistently positively associated with breast cancer risk in epidemiologic studies and the association generally appears stronger among estrogen receptor (ER) positive tumors. However, the underlying biologic mechanism is not completely understood. Methods: We evaluated pre-diagnostic alcohol intake in relation to transcriptome profiles of invasive breast cancers diagnosed 1990-2009 in the Nurses’ Health Studies using a custom Affymetrix Human Transcriptome array. RNA was extracted from formalin fixed paraffin embedded breast tumor and tumor adjacent normal tissue. Cumulative average and recent alcohol intake were used in the analysis (defined as categorical: 0, &amp;gt;0 - &amp;lt;10, 10+ g/d or continuous: per 10 g/d). Multivariable linear regression was used to identify differentially expressed genes in tumor (n = 602) and adjacent normal (n = 508) samples, respectively. We further conducted gene set enrichment analysis (GSEA) to assess biological pathways. Differentially expressed genes or gene sets were considered statistically significant if false discovery rate &amp;lt; 0.1. Results: When comparing cumulative average or recent alcohol intake 10+ g/d vs. 0, no significantly differentially expressed genes were identified in all tumors combined or in stratified analyses by ER or human epidermal growth factor receptor 2(HER2) status. However, when recent alcohol assessed as per 10 g/d, SUSD2 was significantly up-regulated and GTPBP6 significantly down-regulated in HER2+ and ER- tumors, respectively. No genes were significantly differentially expressed according to alcohol intake in tumor adjacent normal tissue. When evaluating recent alcohol intake 10+ g/d vs 0, differentially expressed gene sets identified through GSEA suggest that translation, cell cycle, and response to DNA damage and DNA repair were up-regulated while lipid metabolism and signaling and retinol metabolism were down-regulated in ER+ tumors; in ER- tumors, immune function/inflammatory response was up-regulated in addition to the up-regulation of genes involved in translation and cell-cycle. We further verified these gene sets (n = 32 and 4 up- and down- regulated, respectively in ER+ tumors; n = 89 and 2 up- and down-, respectively in ER- tumors) in The Cancer Genome Atlas data set. However, such differentially expressed gene sets were not observed in the analysis of cumulative average alcohol. In tumor adjacent normal samples, in addition to the down-regulation in lipid metabolism and signaling (consistent with ER+ tumors), alcohol metabolism (particularly in mitochondria), DNA damage response and apoptosis were significantly down-regulated (contrary to ER+ tumors), when comparing recent alcohol 10+ g/d vs. 0. Conclusion: To the best of our knowledge, this is the first study to evaluate pre-diagnostic alcohol consumption and breast tumor transcriptomic profiles. Assessment of transcriptomic differences with alcohol intake in tumor and/or adjacent normal tissue may help provide insights into the biologic mechanism underlying the alcohol and breast cancer association. Citation Format: Jun Wang, Yujing J. Heng, Aditi Hazra, A. Heather Eliassen, Rulla Tamimi, David Hunter, Andrew Beck, Susan Hankinson. Alcohol consumption and transcriptomic differences in breast tumor. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-380.