Empirical Dietary Inflammatory Pattern Scores Research Articles

Prospective Analyses of Lifestyle Factors Related to Energy Balance and Ovarian Cancer Risk by Infiltration of Tumor-Associated Macrophages.

Lifestyle factors related to energy balance have been associated with ovarian cancer risk and influence the tumor immune microenvironment, including tumor-associated macrophages (TAM). However, no studies have assessed whether these factors differentially impact ovarian cancer risk by TAM densities. We conducted a prospective analysis in the Nurses' Health Studies to examine the associations of physical activity, sitting time, and a food-based empirical dietary inflammatory pattern (EDIP) score with invasive epithelial ovarian cancer risk by TAM density assessed by immunohistochemistry. We considered density of CD68 (marker of total TAMs) and CD163 (marker of pro-carcinogenic M2-type TAMs), and their ratios. We used multivariable Cox proportional hazards regression to calculate hazard ratios (HR) and 95% confidence intervals (CI) of exposures with risk of ovarian tumors with high versus low TAMs, including analyses stratified by body mass index. Analyses included 312 incident ovarian cancer cases with TAM measurements. Physical activity, sitting time, and EDIP score were not differentially associated with ovarian cancer risk by TAM densities (P heterogeneity > 0.05). Among overweight and obese women, higher EDIP score was associated with increased risk of CD163 low-density tumors (HR comparing extreme tertiles, 1.57; 95% CI, 0.88-2.80; P trend = 0.01), but not CD163 high-density tumors (comparable HR, 1.16; 95% CI, 0.73-1.86; P trend = 0.24), though this difference was not statistically significant (P heterogeneity = 0.22). We did not observe differential associations between lifestyle factors and ovarian cancer risk by TAM densities. Future investigations examining the interplay between other ovarian cancer risk factors and the tumor immune microenvironment may help provide insight into ovarian cancer etiology.

The relationship between inflammatory dietary pattern and incidence of periodontitis.

The long-term inflammatory impact of diet could potentially elevate the risk of periodontal disease through modification of systemic inflammation. The aim of the present study was to prospectively investigate the associations between a food-based, reduced rank regression (RRR)-derived, empirical dietary inflammatory pattern (EDIP) and incidence of periodontitis. The study population was composed of 34940 men from the Health Professionals Follow-Up Study, who were free of periodontal disease and major illnesses at baseline (1986). Participants provided medical and dental history through mailed questionnaires every 2 years and dietary data through validated semi-quantitative FFQ every 4 years. We used Cox proportional hazard models to examine the associations between EDIP scores and validated self-reported incidence of periodontal disease over a 24-year follow-up period. No overall association between EDIP and the risk of periodontitis was observed; the hazard ratio comparing the highest EDIP quintile (most proinflammatory diet) with the lowest quintile was 0·99 (95 % CI 0·89, 1·10, P-value for trend = 0·97). A secondary analysis showed that among obese non-smokers (i.e. never and former smokers at baseline), the hazard ratio for periodontitis comparing the highest EDIP quintile with the lowest was 1·39 (95 % CI 0·98, 1·96, P-value for trend = 0·03). In conclusion, no overall association was detected between EDIP and incidence of self-reported periodontitis in the study population. From the subgroups evaluated, EDIP was significantly associated with increased risk of periodontitis only among non-smokers who were obese. Hence, this association must be interpreted with caution.

Higher empirical dietary inflammatory pattern scores are associated with worse cognitive performance in the Nurses’ Health Study

AbstractBackgroundWe evaluated whether higher cumulative Empirical Dietary Inflammatory Pattern (EDIP) scores were associated lower cognitive function, in the Nurses’ Health Study.Method16,058 post‐menopausal women (mean age 74 (Standard deviation, 2)) completed a validated 116‐item Food Frequency Questionnaire. The EDIP score, previously derived with the use of reduced rank regression to predict circulating inflammatory markers (i.e. C‐reactive protein, tumor necrosis factor α receptor 2 and interleukin‐6), consists of ten anti‐inflammatory and nine pro‐inflammatory components. A cumulative EDIP score was calculated by averaging across five exams (1984‐1998) taking the first exam (1984) or second exam (1986) as baseline exams. The EDIP score was categorized into five quintiles, taking the first (anti‐inflammatory) quintile as the reference category. Cognitive testing was performed through telephone interviews over four follow up exams (1995‐2008). A composite global cognition score, a composite verbal memory score and the Telephone Interview for Cognitive Status (TICS) were calculated and averaged across the four exams.ResultHigher cumulative EDIP scores (i.e. more pro‐inflammatory) were significantly associated with worse performance on global cognitive function (p for trend <0.01) and TICS (p for trend <0.001) after adjustment for age, education and body mass index, physical activity, energy intake, smoking, multivitamin use, depression. The relationship between higher cumulative EDIP scores and TICS remained (p for trend 0.04) following additional adjustments for hypertension, high cholesterol, myocardial infarction, diabetes, menopausal hormone use and nonsteroidal anti‐inflammatory drugs. But the association between the EDIP score and global cognitive function attenuated and became non‐significant. No association was observed between the EDIP score and verbal memory.ConclusionHigher cumulative EDIP scores strongly associated with worse performance on averaged TICS regardless of the model among older women. But the relationships between the EDIP score and global cognitive function and verbal memory were mainly explained by potential confounders and intermediates leaving findings attenuated and not significant. Our study shows that pro‐inflammatory diets not only are detrimental for risk factors of cognitive decline but also for cognitive function itself. Future studies are encouraged to investigate the relationships in men and over a long follow up period.

Abstract PO-142: Development of Empirical Dietary Inflammatory Pattern (EDIP) scores with different food groups and biomarkers

Abstract Background: The empirical dietary inflammatory pattern (EDIP) is a hypothesis- driven dietary pattern used to assess the inflammatory potential of diet in the US population. It is usually composed of food groups obtained from a food-frequency questionnaire. Methods: EDIP scores were calculated for 4 models from 24hr recalls reported by 67 women noncancer controls that had signed an informed consent prior to participation. The Luminex Human Chemokine Multiplex Assay was used to measure 11 chemokines and cytokines. As seen in previous studies, we first derived a model, EDIP-Limited (EDIP-L), by entering 18 food groups in reduced rank regression models followed by a multivariable regression analysis to identify a dietary pattern that predicts concentrations of two inflammatory biomarkers: IL-6 and TNF-a. We derived another EDIP score using a new model, EDIP-All Inclusive (EDIP-AI), which included the same 18 food groups to predict all 11 biomarkers. Lastly, we developed two other EDIP models. EDIP-Limited New (EDIP-LN) used 14 new food groups derived from the same 24hr recalls, only predicting IL-6 and TNF-a. EDIP-All New (EDIP-AN) used those 14 food groups with all 11 biomarkers. Results: In this study, we optimize models for EDIP and report the differences in EDIP scores based on the inflammatory biomarkers and food groups used in analysis. Briefly, the components of EDIP-L were not significant. After including all the biomarkers, the components of EDIP-AI were: “fruit juice” (p = 0.0009), “snacks” (p = 0.0008), “leafy green vegetables” (p = 0.0074), “low-energy beverages” (p = 0.0098), “red meat” (p = 0.0038), “fruit” (p = 0.0002) and “whole wheat grains” (p = 0.0138). Similarly, after reorganizing our food items into 14 food groups, the components of EDIP-LN were not significant. However, components of EDIP-AN were: “fruit juice” (p = 0.0107), “snacks” (p = 0.0116) and “fruit” (p = 0.0026). Conclusions: Findings demonstrate the EDIP scores differ based on the inflammatory biomarkers and food groups used in the analysis on the same noncancer controls. Depending on the methods used, an individual’s diet may be considered more pro- or anti-inflammatory. This study provides insight into the inflammatory potential of an individual’s diet and the factors that may affect how we calculate this potential. Citation Format: Emma Guyonnet, Millicent Amankwah, Yalei Chen, Rachel Martini, Melissa Davis, Lisa Newman. Development of Empirical Dietary Inflammatory Pattern (EDIP) scores with different food groups and biomarkers [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-142.

Dietary Inflammatory Potential and Risk of Cardiovascular Disease Among Men and Women in the U.S.

BackgroundInflammation plays an important role in cardiovascular disease (CVD) development. Diet modulates inflammation; however, it remains unknown whether dietary patterns with higher inflammatory potential are associated with long-term CVD risk. ObjectivesThis study sought to examine whether proinflammatory diets are associated with increased CVD risk. MethodsWe prospectively followed 74,578 women from the Nurses’ Health Study (NHS) (1984–2016), 91,656 women from the NHSII (1991–2015), and 43,911 men from the Health Professionals Follow-up Study (1986–2016) who were free of CVD and cancer at baseline. Diet was assessed by food frequency questionnaires every 4 years. The inflammatory potential of diet was evaluated using a food-based empirical dietary inflammatory pattern (EDIP) score that was pre-defined based on levels of 3 systemic inflammatory biomarkers. ResultsDuring 5,291,518 person-years of follow-up, we documented 15,837 incident CVD cases, including 9,794 coronary heart disease (CHD) cases and 6,174 strokes. In pooled analyses of the 3 cohorts, after adjustment for use of anti-inflammatory medications and CVD risk factors including body mass index, a higher dietary inflammatory potential, as indicated by higher EDIP scores, was associated with an increased risk of CVD (hazard ratio [HR] comparing the highest to lowest quintiles: 1.38; 95% confidence interval [CI]: 1.31 to 1.46; p for trend <0.001), CHD (HR: 1.46; 95% CI: 1.36 to 1.56; p for trend <0.001), and stroke (HR: 1.28; 95% CI: 1.17- to 1.39; p for trend <0.001). These associations were consistent across cohorts and between sexes, and they remained significant after further adjustment for other dietary quality indices. In a subset of study participants (n = 33,719), a higher EDIP was associated with a higher circulating profile of proinflammatory biomarkers, lower levels of adiponectin, and an unfavorable blood lipid profile (p < 0.001). ConclusionsDietary patterns with a higher proinflammatory potential were associated with higher CVD risk. Reducing the inflammatory potential of the diet may potentially provide an effective strategy for CVD prevention.

Dietary Inflammatory Potential and Risk of Crohn’s Disease and Ulcerative Colitis

Inflammation is a potential mechanism through which diet modulates the onset of inflammatory bowel disease. We analyzed data from 3 large prospective cohorts to determine the effects of dietary inflammatory potential on the risk of developing Crohn's disease (CD) and ulcerative colitis (UC). We collected data from 166,903 women and 41,931 men in the Nurses' Health Study (1984-2014), Nurses' Health Study II (1991-2015), and Health Professionals Follow-up Study (1986-2012). Empirical dietary inflammatory pattern (EDIP) scores were calculated based on the weighted sums of 18 food groups obtained via food frequency questionnaires. Self-reported CD and UC were confirmed by medical record review. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). We documented 328 cases of CD and 428 cases of UC over 4,949,938 person-years of follow-up. The median age at IBD diagnosis was 55 years (range 29-85 years). Compared with participants in the lowest quartile of cumulative average EDIP score, those in the highest quartile (highest dietary inflammatory potential) had a 51% higher risk of CD (HR 1.51; 95% CI 1.10-2.07; Ptrend= .01). Compared with participants with persistently low EDIP scores (at 2 time points, separated by 8 years), those with a shift from a low to high inflammatory potential of diet or persistently consumed a proinflammatory diet had greater risk of CD (HR 2.05; 95% CI 1.10-3.79 and HR 1.77; 95% CI 1.10-2.84). In contrast, dietary inflammatory potential was not associated with the risk of developing UC (Ptrend= .62). In an analysis of 3 large prospective cohorts, we found dietary patterns with high inflammatory potential to be associated with increased risk of CD but not UC.

Abstract 26: Polygenic Risk Score for Obesity Modifies Associations of Proinflammatory Diets With Obesity, Long-term Weight Gain, and Cardiovascular Disease Risk: The Utilization of Polygenic Prediction in 3 US Prospective Cohorts

Background: Individuals predisposed to higher genetic risk of obesity may need early dietary interventions to prevent obesity and its comorbidities. Hypothesis: Proinflammatory diets may interact with genetic background to modify risks of obesity, long-term weight gain, and cardiovascular disease (CVD). Methods: We prospectively followed 16 281 and 11 832 women in the Nurses’ Health Study I and II, and 10 172 men in Health Professionals Follow-up Study, with available genetic data, for up to 28 years. Diet and weight were assessed every 4 years. Dietary inflammatory potential was assessed by an empirical dietary inflammatory pattern (EDIP) score pre-defined based on associations of foods with inflammatory markers. Polygenic risk scores (PRS) of body mass index (BMI), waist-hip ratio, and body fat mass, developed based on genome-wide association data of 9 million variants in 389 972 UK Biobank participants using LDpred, were applied to characterize genetic predispositions to obesity, central obesity, and adiposity. Results: All 3 PRS were highly predictive for BMI ( Fig. A ). In pooled multivariable analyses, higher EDIP scores were associated with a higher BMI, with the association 2-3 folds stronger comparing participants in the highest 10% to the lowest 10% of genetic risk of obesity/adiposity ( P interaction ≤0.001; Fig. B ). The positive association between EDIP and CVD incidence was 1.6-fold stronger in participants at a higher genetic risk of central obesity ( P interaction =0.04; Fig. C ). In addition, an increase in EDIP scores was associated with a greater long-term weight gain, while a reduction in EDIP was associated with a greater weight loss, comparing participants in the highest 10% of genetic risk to those at lower risks, among participants aged &lt;65 years but not above ( P interaction &lt;0.005; Fig. D ). Conclusions: Polygenic background modifies associations of proinflammatory diets with obesity, long-term weight change, and CVD risk. PRS may be useful tools to identify individuals in need for early dietary interventions.

The association between diet quality and obesity-related metabolic risks.

The aim of this study was to examine the association between dietary quality measured by inflammatory potential of a diet and Alternative Healthy Eating Index-2010 (AHEI-2010), and obesity-related metabolic risks in a representative sample of Iranian obese adults. This cross-sectional study was conducted on 300 obese adults. Dietary intake was assessed using a validated 168-item semi-quantitative food frequency questionnaire (FFQ). Diet quality was measured using AHEI-2010 and Empirical Dietary Inflammatory Pattern (EDIP) scores. Those in the upper quartile of AHEI-2010 were associated with lower serum level of triglycerides (TG), and higher body mass index (BMI), compared to participants in the lower quartile. Those in the higher quartile of EDIP score were associated with higher serum level of TG. Greater adherence to AHEI-2010 had 70% lower odds of high fasting blood glucose (FBG), compared with those in the first quartile [Q4 vs Q1: OR, 0.3 (95% CI: 0.1-0.8), p trend = 0.02] Those in the highest quartile of EDIP score had a 60% higher odds of high diastolic blood pressure, compared with those in the lowest quartile [Q4 vs Q1: OR, 2.4 (95% CI: 1.1-5.5), p trend = 0.05] after controlling for potential covariates. High diet quality incorporating more anti-inflammatory diet may have a potential benefit in reducing obesity-related metabolic risks.

Association between Inflammatory Potential of Diet and Bladder Cancer Risk: Results of 3 United States Prospective Cohort Studies.

Inflammatory reaction has been linked to bladder cancer. Diet, which drives systemic inflammation, may be considered a modifiable risk factor for bladder cancer. We examined the association of diet with pro-inflammatory potential and bladder cancer risk using the novel EDIP (empirical dietary inflammatory pattern) score comprising predefined food groups determining a pattern most predictive of plasma inflammatory markers. We followed a total of 172,802 women in the NHS (Nurses' Health Study) from 1984 to 2012 and the NHS II from 1991 to 2013 as well as 45,272 men in the HPFS (Health Professionals Follow-Up Study) from 1986 to 2012. Multivariable adjusted Cox regression models were used to estimate the RR and 95% CI of bladder cancer across EDIP score quintiles. We performed inverse variance weighted meta-analysis to pool estimates across cohorts stratified by smoking status. During 4,872,188 person-years of observation 1,042 incident bladder cancer cases were identified. Overall, high EDIP scores reflecting dietary patterns with pro-inflammatory potential were not associated with a higher risk of bladder cancer (quintile 5 vs 1 pooled multivariable adjusted RR 0.92, 95% CI 0.75-1.12, ptrend = 0.67). Results were consistent across individual cohorts (quintile 5 vs 1 in the NHS RR 1.04, 95% CI 0.78-1.37, ptrend = 0.71; in the NHS II RR 1.44, 95% CI 0.53-3.91, ptrend = 0.13; and in the HPFS RR 0.74, 95% CI 0.55-1.01, ptrend = 0.11). Results were similar regardless of smoking status. We observed no association between diets with pro-inflammatory potential and bladder cancer risk. Although additional studies are needed to explore other nutritional pathways with the potential for bladder cancer prevention, our results suggest that diets associated with inflammation are not associated with bladder cancer risk.

Identifying metabolomic profiles of inflammatory diets in postmenopausal women

We previously showed that a food-based empirical dietary inflammatory pattern (EDIP) score is associated with circulating inflammatory biomarkers. Metabolomic profiling of inflammatory diets may therefore provide insights on mechanisms contributing to disease etiology and prognosis. We aimed to elucidate metabolites associated with inflammatory diets among postmenopausal women, utilizing a robust study design that incorporates independent discovery and validation datasets. This baseline cross-sectional investigation evaluated associations between continuous EDIP scores calculated from food frequency questionnaires and 448 log-transformed plasma metabolites as outcomes in multivariable-adjusted linear regression analyses. Metabolites were measured with liquid chromatography tandem mass spectroscopy. Metabolite discovery was conducted among 1109 Women's Health Initiative (WHI) Hormone Therapy trial participants and results were replicated in an independent dataset of 810 WHI Observational Study participants. Secondary analyses were stratified by standard body mass index (BMI, kg/m2) categories. In discovery and replication datasets statistical significance was based on false-discovery rate adjusted P<0.05. After adjusting for energy intake, BMI, physical activity, and other confounding variables, 23 metabolites were significantly associated with EDIP score in the discovery dataset. Of these, the following ten were replicated: trigonelline, caffeine, acethylamino-6-amino-3-methyluracil, 7-methylxanthine, 1,7-dimethyluric acid, 3-methylxanthine, C18:3CE, glycine, associated with lower dietary inflammatory potential; whereas C52:3 triacylglycerol and linoleate associated with higher dietary inflammatory potential. Four of the ten were associated [glycine (inversely), caffeine, 1,7-dimethyluric acid, C52:3 triacylglycerol, (positively)], with C-reactive protein levels. In secondary analyses, associations showed differences by BMI category. Four metabolites, related to coffee/caffeine metabolism were inversely associated among normal weight women, and 83 metabolites associated with EDIP among overweight/obese women, including 40 (48%) that were also associated with C-reactive protein. Metabolites associated with coffee/caffeine and lipid metabolism may reflect the inflammatory potential of diet. Potential differences by BMI and the linkage to disease outcomes, require further study.

Abstract 030: Dietary Inflammatory Potential is Associated with Cardiovascular Disease Risk in Two Large Prospective Cohort Studies of US Men and Women

Introduction: Chronic inflammation plays a pathogenic role in cardiovascular disease (CVD) development. Dietary factors have been implicated in CVD etiology and may have an impact on chronic inflammation. Hypothesis: Proinflammatory diets are associated with higher CVD risk. Methods: We include74,544 women in the Nurses’ Health Study (from 1984 through 2012) and 43,904 men in the Health Professionals Follow-up Study (from 1986 through 2012), who were free of heart disease, stroke, and cancer at baseline. Dietary inflammatory potentials were assessed using an empirical dietary inflammatory pattern (EDIP) score that has been pre-defined by 18 food components based on their associations with circulating levels of systemic inflammation markers C-reactive protein, interleukin-6, and tumor necrosis factor-α receptor 2. Adjusted hazard ratios (HRs) and 95% confidence internals (CIs) for CVD were calculated using Cox regressions. Results: During 2,831,128 person-years of follow-up, we documented 13,249 incident CVD cases, including 8,178 coronary heart disease cases and 5,182 stroke cases. After adjusting for established risk factors and potential confounders including body-mass index and aspirin or other nonsteroidal anti-inflammatory medication use, a higher EDIP score was associated with an increased risk of CVD (in pooled analyses, HR [95% CI] comparing the highest to the lowest quintiles were 1.29 [1.22 to 1.37]; P trend &lt;0.001), CHD (HR = 1.32[1.23 to 1.42]; P trend &lt;0.001), and stroke (HR = 1.25 [1.14 to 1.37]; P trend &lt;0.001). Associations were similar among subgroups of participants, including by age, sex, family history, BMI, physical activity, and alcohol intake; but were stronger among non/past-smoking than current smoking women ( P interaction &lt;0.002). Conclusions: Findings from two large US prospective cohort studies suggest that inflammation may be a potential mechanism linking dietary patterns to CVD progression. Reducing the proinflammatory potentials of the diet may assist CVD prevention.

Empirical dietary inflammatory pattern and risk of metabolic syndrome and its components: Tehran Lipid and Glucose Study

BackgroundThe rising incidence of metabolic syndrome (MetS) is a major public health problem. The inflammatory potential of diet contributes to the development of MetS. The aim of this study was to investigate the relationship between empirical dietary inflammatory pattern (EDIP) and risk of MetS among the Tehranian population. Our hypothesis was that high EDIP would increase the risk of MetS and its components.MethodsIn this prospective study, 2216 adults were selected from among the Tehran Lipid and Glucose Study participants. The usual dietary intakes were estimated using a valid and reliable food frequency questionnaire. Biochemical and anthropometric measurements were assessed at baseline and over 6.2 years of follow up. MetS components were defined according to the modified national Cholesterol Education Program Adult Treatment Panel III. The inflammatory potential of diet was calculated using EDIP score; more positive scores means higher pro-inflammatory diet. Adjusted logistic regression models were used to estimate the occurrence of MetS and its components across quartiles of EDIP score.ResultsMean ± SD for EDIP score was 0.61 ± 0.40 (range − 2.3 to 6.9). Participants with the highest EDIP scores, had a higher risk of MetS incidence compared to those with the lowest score (OR: 1.75, 95% CI 1.21–2.54, Ptrend = 0.003). Among the MetS components, hyperglycemia, abdominal obesity, and low HDL-C had a significant positive association with EDIP score; (OR: 1.46, 95% CI 1.03–2.08, Ptrend = 0.026), (OR: 1.43, 95% CI 1.03–1.97, Ptrend = 0.046), and (OR: 1.57, 95% CI 1.34–2.19, Ptrend = 0.015), respectively. No significant association was found between EDIP score, hypertension and hypertriglyceridemia.ConclusionOur finding indicated that higher intake of the pro-inflammatory diet may be an independent risk factor for the development of MetS, hyperglycemia, low HDL-C and abdominal obesity in Tehranian adults.

The association between the inflammatory potential of diet and risk of developing, and survival following, a diagnosis of ovarian cancer.

Inflammation has been implicated in ovarian carcinogenesis. This study evaluated two dietary indices: the Dietary Inflammatory Index (DII®) and the Empirical Dietary Inflammatory Pattern (EDIP), in relation to risk of developing, and survival following, a diagnosis of ovarian cancer. Data came from the Australian Ovarian Cancer Study (1375 cases, 1415 population controls). DII and EDIP scores were computed from dietary information obtained using a semiquantitative food-frequency questionnaire. Logistic regression was used to assess the association between DII and EDIP scores and risk of ovarian cancer and proportional hazards models were used for survival analysis. A high DII score, reflecting a more pro-inflammatory diet, was associated with a modest increased risk of ovarian cancer [odds ratio (OR) DII scoreQ4 vs.Q1 = 1.31, 95% CI 1.06-1.63, ptrend = 0.014]. Likewise a high EDIP score was associated with an increase in risk of ovarian cancer [OR EDIP scoreQ4 vs.Q1 = 1.39, 95% confidence interval (CI) 1.12-1.73, ptrend = 0.002]. We found no association between DII or EDIP score and overall or ovarian cancer-specific survival. In conclusion, our results suggest that a pro-inflammatory diet modestly increases the risk of developing ovarian cancer.

Abstract 5256: A prospective study of inflammatory diet potential and risk of hepatocellular carcinoma (HCC)

Abstract Worldwide, hepatocellular carcinoma (HCC) is the fifth most common cancer and the second-leading cause of cancer-related death worldwide. In the U.S., the incidence rate of HCC has tripled since 1975. Although preliminary evidence suggesting a biological impact of diet on multiple inflammatory pathways implicated in hepatocarcinogenesis, the most comprehensive review by the WCRF/AICR concluded that the relationship between diet and HCC remains largely unknown. HCC is an inflammation-related cancer but few studies have investigated diet quality based on its inflammatory potential in relation to HCC risk. The empirical dietary inflammatory pattern scores (EDIP) score were calculated from validated food frequency questionnaires. It characterized dietary inflammatory potential based on circulating levels of inflammatory bio-markers. We prospectively followed 49,674 men in the Health Professionals Follow-up Study (1986-2012), and 74,139 women in the Nurses' Health Study (1984-2012). Cox regression analyses were used to calculate hazards ratios (HR) for HCC risk adjusting for body mass index, smoking, history of diabetes, race, physical activity, and regular aspirin use. We documented a total of 89 incident HCC cases (44 in women and 45 in men) over 28 years, encompassing 1,522,972 person-years of follow-up. Compared to the lowest tertile, the highest tertile of the EDIP score was associated with a multivariable HR for HCC of 2.86 (95%CI, 1.20-6.81) among women (P-trend=0.01) and of 0.68 (95%CI, 0.31-1.50) among men (P-trend=0.35). Future study is warranted to confirm this finding and elucidate the potential biological basis. Key words: inflammation, dietary patterns, HCC A. T. C. and X. Z contributed equally to this work. Citation Format: Yanan Ma, Tracey G. Simon, Fred K Tabung, Lindsay Y. King, Dawn Q. Chong, Long Nguyen, Trang VoPham, Charles S. Fuchs, Jeffrey A. Meyerhardt, Kathleen E. Corey, Hamed Khalili, Stephanie Smith-Warner, Raymond T. Chung, Edward L. Giovannucci, Andrew T. Chan, Xuehong Zhang. A prospective study of inflammatory diet potential and risk of hepatocellular carcinoma (HCC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5256.

An Empirical Dietary Inflammatory Pattern Score Is Associated with Circulating Inflammatory Biomarkers in a Multi-Ethnic Population of Postmenopausal Women in the United States

The empirical dietary inflammatory pattern (EDIP) score has been associated with concentrations of circulating inflammatory biomarkers in European Americans. We used the EDIP score, a weighted sum of 18 food groups that characterizes dietary inflammatory potential based on circulating concentrations of inflammatory biomarkers, to test the hypothesis that a pro-inflammatory dietary pattern is associated with inflammatory biomarker concentrations in a US multi-ethnic population. In this cross-sectional study, we calculated EDIP scores using baseline food frequency questionnaire data from 31,472 women, aged 50-79 y, in the Women's Health Initiative observational study and clinical trials. Circulating biomarkers outcomes at baseline were: C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor (TNF)-α, TNF receptor (TNFR) 1 and 2, and adiponectin. We used multivariable-adjusted linear regression analyses to estimate absolute concentrations and relative differences in biomarker concentrations, overall and in subgroups of race/ethnicity and BMI (body mass index) categories. Independent of energy intake, BMI, physical activity, and other potential confounding variables, higher EDIP scores were significantly associated with higher (lower for adiponectin) absolute concentrations of all 6 biomarkers. On the relative scale, the percentage of difference in the concentration of biomarkers, among women in the highest compared to the lowest EDIP quintile, was: CRP, +13% (P-trend<0.0001); IL-6, +15% (P-trend<0.0001); TNF-α, +7% (P-trend=0.0007); TNFR1, +4% (P-trend=0.0009); TNFR2, +5% (P-trend<0.0001); and adiponectin, -13% (P-trend <0.0001). These associations differed by racial/ethnic groups and by BMI categories. Whereas the absolute biomarker concentrations were lower among European-American women and among normal-weight women, the associations with diet were stronger than among women of African-American or Hispanic/Latino origin and among overweight and obese women. Findings demonstrate the successful replication of an empirical hypothesis-oriented a posteriori dietary pattern score in a multi-ethnic population of postmenopausal women, with subgroup differences by race/ethnicity and body weight. Future research needs to apply the score in non-US populations.

The Association Between Empirical Dietary Inflammatory Pattern and Metabolic Phenotypes in Overweight/Obese Adults.

ObjectivesThe study aimed to investigate whether diet-induced inflammation assessed by Empirical Dietary Inflammatory Pattern (EDIP) is associated with odds of unhealthy metabolic phenotype and components of metabolic syndrome (MetS).MethodsThis cross-sectional study included 403 overweight/obese individuals recruited from employees of two pharmaceutical companies in Iran. The weighted intake of 15 food groups was summed to construct EDIP and metabolic phenotypes were defined based on MetS criteria.ResultsAfter adjusting for age, sex, BMI, and marital status, the odds of unhealthy phenotype increased significantly from quartile 1 to quartile 4 (P-trend = 0.013). However, the association became non-significant after adjusting for energy intake. Compared to those in the lowest quartile, individuals with higher EDIP scores had higher odds of high fasting blood sugar (FBS) (P-trend = 0.031) and low HDL-C (P-trend = 0.036) after adjusting for all covariates. By adding energy intake into the model, an inverse association was observed between EDIP, waist circumference (WC), and odds of high WC.ConclusionsA higher pro-inflammatory diet was associated with higher odds of unhealthy phenotype, high FBS, and low-HDL-C in overweight/obese individuals. However, the association with unhealthy phenotype seems to be dependent on the energy intake.

Association of Dietary Inflammatory Potential With Colorectal Cancer Risk in Men and Women

ImportanceInflammation is important in colorectal cancer development. Diet modulates inflammation and may thus be a crucial modifiable factor in colorectal cancer prevention.ObjectiveTo examine whether proinflammatory diets are associated with increased colorectal cancer risk by using an empirical dietary inflammatory pattern (EDIP) score based on a weighted sum of 18 food groups that characterizes dietary inflammatory potential based on circulating levels of inflammation biomarkers.Design, Settings, and ParticipantsCohort study of 46 804 men (Health Professionals Follow-up Study: 1986-2012) and 74 246 women (Nurses’ Health Study: 1984-2012) followed for 26 years to examine associations between EDIP scores and colorectal cancer risk using Cox regression. We also examined associations in categories of alcohol intake and body weight. Data analysis began January 17, 2017, and was completed August 9, 2017.ExposuresEDIP scores calculated from food frequency questionnaires administered every 4 years.Main Outcomes and MeasuresIncident colorectal cancer.ResultsWe documented 2699 incident colorectal cancer cases over 2 571 831 person-years of follow-up. Compared with participants in the lowest EDIP quintile (Q) who had a colorectal cancer incidence rate (per 100 000 person-years) of 113 (men) and 80 (women), those in the highest Q had an incidence rate of 151 (men) and 92 (women), leading to an unadjusted rate difference of 38 and 12 more colorectal cancer cases, respectively, among those consuming highly proinflammatory diets. Comparing participants in the highest vs lowest EDIP Qs in multivariable-adjusted analyses, higher EDIP scores were associated with 44% (men: hazard ratio [HR], 1.44; 95% CI, 1.19-1.74; P < .001 for trend), 22% (women: HR, 1.22; 95% CI, 1.02-1.45; P = .007 for trend), and 32% (men and women: pooled HR, 1.32; 95% CI, 1.12-1.55; P < .001 for trend) higher risk of developing colorectal cancer. In both men and women, associations were observed in all anatomic subsites except for the rectum in women. In subgroups (P ≤ .02 for all interactions), associations differed by alcohol intake level, with stronger associations among men (Q5 vs Q1 HR, 1.62; 95% CI, 1.05-2.49; P = .002 for trend) and women (Q5 vs Q1 HR, 1.33; 95% CI, 0.97-1.81; P = .03 for trend) not consuming alcohol; and by body weight, with stronger associations among overweight/obese men (Q5 vs Q1 HR, 1.48; 95% CI, 1.12-1.94; P = .008 for trend) and lean women (Q5 vs Q1 HR, 1.31; 95% CI, 0.99-1.74; P = .01 for trend).Conclusions and RelevanceFindings suggest that inflammation is a potential mechanism linking dietary patterns and colorectal cancer development. Interventions to reduce the adverse role of proinflammatory diets may be more effective among overweight/obese men and lean women or men and women who do not consume alcohol.

Covering the Cover

Covering the Cover

Association Between Inflammatory Diet Pattern and Risk of Colorectal Carcinoma Subtypes Classified by Immune Responses to Tumor

Dietary patterns affect systemic and local intestinal inflammation, which have been linked to colorectal carcinogenesis. Chronic inflammation can interfere with the adaptive immune response. We investigated whether the association of a diet that promotes intestinal inflammation with risk of colorectal carcinoma was stronger for tumors with lower lymphocytic reactions than tumors with higher lymphocytic reactions. We collected data from the molecular pathological epidemiology databases of 2 prospective cohort studies: the Nurses' Health Study (since 1976) and the Health Professionals Follow-Up Study (since 1986). We used duplication-method time-varying Cox proportional cause-specific hazards regression to assess the association of empirical dietary inflammatory pattern (EDIP) score (derived from food frequency questionnaire data) with colorectal carcinoma subtype. Foods that contribute to high EDIP scores include red and processed meats, refined grains, carbonated beverages, and some vegetables; foods that contribute to low EDIP scores include beer, wine, coffee, tea, yellow and leafy vegetables, and fruit juice. Colorectal tissue samples were analyzed histologically for patterns of lymphocytic reactions (Crohn's-like lymphoid reaction, peritumoral lymphocytic reaction, intratumoral periglandular reaction, and tumor-infiltrating lymphocytes). During follow-up of 124,433 participants, we documented 1311 incident colon and rectal cancer cases with available tissue data. The association between the EDIP and colorectal cancer risk was significant (Ptrend= .02), and varied with degree of peritumoral lymphocytic reaction (Pheterogeneity < .001). Higher EDIP scores were associated with increased risk of colorectal cancer with an absent or low peritumoral lymphocytic reaction (highest vs lowest EDIP score quintile hazard ratio, 2.60; 95% confidence interval, 1.60-4.23; Ptrend < .001), but not risk of tumors with intermediate or highperitumoral lymphocytic reaction (Ptrend > .80). In 2 prospective cohort studies, we associated inflammatory diets with a higher risk of colorectal cancer subtype that contains little or no peritumoral lymphocytic reaction. These findings suggest that diet-related inflammation might contribute to development of colorectal cancer, by suppressing the adaptive anti-tumor immune response.

The inflammatory potential of diet and ovarian cancer risk: results from two prospective cohort studies

Background:We used a food-based empirical dietary inflammatory pattern (EDIP) score to investigate whether diets with higher inflammatory potential are associated with increased ovarian cancer risk.Methods:We followed 186 314 women in the Nurses’ Health Study and Nurses’ Health Study-II, from 1984 to 2013, to examine associations between EDIP scores and ovarian cancer risk, using Cox regression analyses.Results:During 3 454 514 person-years of follow-up, 989 ovarian cancer cases were identified. In pooled multivariable-adjusted analyses, higher EDIP scores (more pro-inflammatory diets) were not significantly associated with ovarian cancer risk (HRquintile5vs1 0.99; 95% CI: 0.80–1.22; P-trend=0.97). Similarly, we found no evidence of heterogeneity by histologic subtype (P-heterogeneity=0.52) or by tumour aggressiveness (P-heterogeneity=0.63).Conclusions:In contrast with two previous case-control studies that found a positive association between a literature-derived nutrient-based dietary inflammatory index and ovarian cancer risk, our prospective analyses using a food-based score observed no evidence of an association.