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C-reactive protein (CRP) and fibrinogen are associated with an increased risk of death with suggested differences by gender, diet quality and race/ethnicity. However, the current evidence is limited. We used data including 8646 men and 9880 women from the National Health and Nutrition Examination Survey (NHANES) Linked Morality cohort (1999–2011) to investigate the associations of CRP and fibrinogen with mortality overall and by gender, race/ethnicity and diet quality. Cox-proportional hazard model was used to quantify the associations. With a median follow-up of 6 years, a strong dose-response relationship was observed between CRP levels and mortality risk in men after multivariable adjustment. For subjects who survived the first two years, the adjusted hazard ratios (HRs) for total mortality across quartiles (from lower to higher) of CRP were 1.97 (95% CI: 0.62–6.33), 1.89 (0.59, 6.06) and 6.34 (2.28–17.7) (P for trend

Background & Aims Lifestyle and dietary risk factors for diverticulitis also have been associated with chronic inflammation. We performed a prospective study of associations among the inflammatory potential of diets, circulating markers of inflammation, and the incidence of diverticulitis. Methods We followed 46,418 men, initially free of diverticulitis, from 1986 through 2014 in the Health Professionals Follow-Up Study. We collected data on empiric dietary inflammatory pattern scores, which indicate the inflammatory potential of diets, and determined their association with the risk of incident diverticulitis using Cox proportional hazards regression. We used blood samples provided by 18,225 participants from 1993 through 1995 to conduct a nested case–control study; we used conditional logistic regression to evaluate prediagnostic plasma levels of markers of inflammation, including C-reactive protein (CRP), interleukin 6 (IL6), and tumor necrosis factor–receptor superfamily member 1B, in 310 diverticulitis cases and 310 matched diverticulitis-free individuals (controls). Results We documented 1110 cases of incident diverticulitis over 992,589 person-years of follow-up. Compared with participants in the lowest quintile of empiric dietary inflammatory pattern scores, men in the highest quintile had a multivariable-adjusted hazard ratio for diverticulitis of 1.31 (95% CI, 1.07–1.60; Ptrend = .01). The association did not differ significantly by strata of body mass index or vigorous activity (P for interaction > .05 for each). In the nested case–control study, plasma levels of CRP and IL6 were associated with risk of diverticulitis. When we compared extreme quintiles, the multivariable-adjusted relative risk for diverticulitis was 1.85 for CRP (95% CI, 1.04–3.30) and 2.04 for IL6 (95% CI, 1.09–3.84). Conclusions In a large prospective cohort of men, we found that the inflammatory potential of diet and prediagnostic plasma levels of markers of inflammation were associated with incident diverticulitis.

The application of metabolomics technology to epidemiological studies is emerging as a new approach to elucidate disease etiology and for biomarker discovery. However, analysis of metabolomics data is complex and there is an urgent need for the standardization of analysis workflow and reporting of study findings. To inform the development of such guidelines, we conducted a survey of 47 cohort representatives from the Consortium of Metabolomics Studies (COMETS) to gain insights into the current strategies and procedures used for analyzing metabolomics data in epidemiological studies worldwide. The results indicated a variety of applied analytical strategies, from biospecimen and data pre-processing and quality control to statistical analysis and reporting of study findings. These strategies included methods commonly used within the metabolomics community and applied in epidemiological research, as well as novel approaches to pre-processing pipelines and data analysis. To help with these discrepancies, we propose use of open-source initiatives such as the online web-based tool COMETS Analytics, which includes helpful tools to guide analytical workflow and the standardized reporting of findings from metabolomics analyses within epidemiological studies. Ultimately, this will improve the quality of statistical analyses, research findings, and study reproducibility.

BackgroundThe limited data on specific dietary components and risk of multiple myeloma (MM) show no consistent association. Studies have not examined the association of dietary pattern with MM risk.MethodsIn prospective cohorts of 69 751 women (Nurses’ Health Study, 1984–2014) and 47 232 men (Health Professionals Follow-up Study, 1986–2014), we examined the association between dietary pattern and risk of MM using Cox proportional hazard models. Diet was assessed repeatedly every 4 years with food frequency questionnaires and was used to calculate dietary patterns including the Alternate Healthy Eating Index-2010, Alternate Mediterranean Diet, Dietary Approaches to Stop Hypertension, Prudent and Western patterns, the empirical dietary inflammatory pattern (EDIP), and empirical dietary indices for insulin resistance (EDIR) and hyperinsulinemia (EDIH).ResultsDuring 2 792 257 person-years of follow-up, we identified 478 incident MM cases (215 women, 263 men). In men, high EDIP was statistically significantly associated with a 16% increase in MM risk (hazard ratio [HR] = 1.16, 95% confidence interval [CI] = 1.02 to 1.32 per 1-SD increase). Moreover, EDIR and EDIH had a suggestive positive association (EDIR: HR = 1.09, 95% CI = 0.96 to 1.24; and EDIH: HR = 1.11, 95% CI = 0.97 to 1.28 per 1-SD increase). We observed no other associations with MM risk in men and no associations for any dietary pattern with MM risk in women.ConclusionsWe present the first evidence for a role of diets with higher inflammatory or insulinemic potential in MM development. Further studies are warranted to explore these associations in other populations, including the apparent restriction to men.

Summary Background 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. Methods 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 Results 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. Conclusion 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.

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 P trend P trend P interaction 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.

Background: The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) 2018 diet, nutrition, and physical activity recommendations aim to reduce cancer risk. We examined adherence to the WCRF/AICR recommendations and colorectal cancer risk in two prospective cohorts. Methods: We followed 68,977 women in the Nurses' Health Study and 45,442 men in the Health Professionals Follow-up Study from 1986 until 2012. We created cumulatively averaged WCRF/AICR scores using updated diet, adiposity, and physical activity data from questionnaires, and used Cox regression to estimate sex-specific HRs and 95% confidence intervals (CI) for incident colorectal cancer. Results: We documented 2,449 colorectal cancer cases. Men in the highest quintile of the WCRF/AICR lifestyle score had a lower risk of colorectal cancer compared with those in the lowest quintile (HRQ5vsQ1 = 0.64; 95% CI, 0.52–0.77). The result was weaker in women (HRQ5vsQ1 = 0.86; 95% CI, 0.72–1.02; Pheterogeneity by sex = 0.006). When analyzing the diet recommendations alone, we similarly observed stronger inverse associations in men (HRQ5vsQ1 = 0.74; 95% CI, 0.61–0.90) compared with women (HRQ5vsQ1 = 0.93; 95% CI, 0.77–1.12; Pheterogeneity by sex = 0.06). In men, the lifestyle score was more strongly inversely associated with risk of distal colon cancer compared with proximal colon or rectal cancer (Pcommon effects = 0.03); we did not observe significant differences between anatomic locations in women. Conclusions: The 2018 WCRF/AICR cancer prevention recommendations are associated with lower colorectal cancer risk in men, with weaker results in women. Impact: Consideration of adiposity and physical activity in conjunction with diet is important for colorectal cancer prevention.

The analysis of dietary patterns has recently drawn considerable attention as a method of investigating the association between the overall whole diet and the risk of colorectal cancer. However, the results have yielded conflicting findings. Here, we carried out a meta-analysis to identify the association between dietary patterns and the risk of colorectal cancer. A total of 40 studies fulfilled the inclusion criteria and were included in this meta-analysis. The highest category of 'healthy' dietary pattern compared with the lowest category was apparently associated with a decreased risk for colorectal cancer [odds ratio (OR)=0.75; confidence interval (CI): 0.68-0.83; P0.00001]. An increased risk of colorectal cancer was shown for the highest compared with the lowest category of a 'western-style' dietary pattern (OR=1.40; CI: 1.26-1.56; P0.00001). There was an increased risk of colorectal cancer in the highest compared with the lowest category of 'alcohol-consumption' pattern (OR=1.44; CI: 1.13-1.82; P=0.003). The results of this meta-analysis indicate that a 'healthy' dietary pattern may decrease the risk of colorectal cancer, whereas 'western-style' and 'alcohol-consumption' patterns may increase the risk of colorectal cancer.

BACKGROUND: The dietary insulin index (II) directly quantifies dietary effects on postprandial insulin secretion, whereas the empirical dietary index for hyperinsulinemia (EDIH), based on fasting C-peptide concentrations, is primarily reflective of insulin resistance. How these scores are related to nonfasting C-peptide in cohort studies has not been examined. OBJECTIVE: We investigated the extent to which EDIH and II scores predict plasma C-peptide concentrations, in cross-sectional analyses by postprandial duration at blood collection from 1 to ≥15 h. METHODS: Both EDIH and II scores were calculated from food-frequency questionnaire data reported by 3964 men in the Health Professionals Follow-up Study (1993–1995) and 6215 women in the Nurses’ Health Study (1989–1990) who were not diabetic. We constructed 12 multivariable-adjusted linear regression models separately in men and women, by postprandial duration, to calculate relative differences and absolute values of plasma C-peptide concentrations in dietary index quintiles. RESULTS: In both men and women, C-peptide concentrations were elevated 1–2 h after eating and declined with increasing postprandial duration. In men, percent differences in C-peptide concentration in the highest compared with lowest dietary index quintile were: EDIH: 0–1 h: 50%; 2 h: 22%; 14 h: 14%; ≥15 h: 30% (all P-trend

Background Diet is a modulator of inflammation that might impact inflammatory skin diseases. Objective To assess the relationship between pro-inflammatory dietary patterns and incident psoriasis, psoriatic arthritis (PsA), and atopic dermatitis (AD). Methods We conducted cohort studies among women in the Nurses' Health Study II. The Empirical Dietary Inflammatory Pattern (EDIP) score was calculated at baseline and every 4 years. Incident psoriasis, PsA, and AD were assessed by validated self-report. We used multivariable-adjusted Cox proportional hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between EDIP quintiles and risk for psoriasis, PsA, and AD. Results We had 85,185 participants in the psoriasis analysis and 63,443 in the AD analysis. There were 1432 cases of psoriasis, 262 cases of PsA, and 403 cases of AD. Pro-inflammatory dietary patterns were not associated with the risk for outcomes in multivariable models (all P values for trend >.05). HRs comparing the highest to the lowest EDIP quintile were 0.99 (95% CI 0.83-1.18) for psoriasis, 1.22 (95% CI 0.81-1.83) for PsA, and 0.96 (95% CI 0.69-1.34) for AD. Limitations Recall and self-report. Conclusion Our findings do not support dietary inflammatory potential as a risk factor for psoriasis, PsA, or AD.

Background: Knowledge on specific biological pathways mediating disease occurrence (e.g., inflammation) may be utilized to construct hypotheses-driven dietary patterns that take advantage of current evidence on disease-related hypotheses and the statistical methods of a posteriori patterns. Objective: We developed and validated an empirical dietary inflammatory index (EDII) based on food groups. Methods: We entered 39 pre-defined food groups in reduced rank regression models followed by stepwise linear regression analyses in the Nurses' Health Study (NHS, n = 5230) to identify a dietary pattern most predictive of 3 plasma inflammatory markers: interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor α receptor 2 (TNFαR2). We evaluated the construct validity of the EDII in 2 independent samples from NHS-II (n = 1002) and Health Professionals Follow-up Study (HPFS, n = 2632) using multivariable-adjusted linear regression models to examine how well the EDII predicted concentrations of IL-6, CRP, TNFαR2, adiponectin, and an overall inflammatory marker score combining all biomarkers. Results: The EDII is the weighted sum of 18 food groups; 9 are anti-inflammatory and 9 proinflammatory. In NHS-II and HPFS, the EDII significantly predicted concentrations of all biomarkers. For example, the relative concentrations comparing extreme EDII quintiles in NHS-II were: adiponectin, 0.88 (95% CI, 0.80, 0.96), P-trend = 0.003; and CRP, 1.52 (95% CI, 1.18, 1.97), P-trend = 0.002. Corresponding associations in HPFS were: 0.87 (95% CI, 0.82, 0.92), P-trend < 0.0001; and 1.23 (95% CI, 1.09, 1.40), P-trend = 0.002. Conclusion: The EDII represents, to our knowledge, a novel, hypothesis-driven, empirically derived dietary pattern that assesses diet quality based on its inflammatory potential. Its strong construct validity in independent samples of women and men indicates its usefulness in assessing the inflammatory potential of whole diets. Additionally, the EDII may be calculated in a standardized and reproducible manner across different populations thus circumventing a major limitation of dietary patterns derived from the same study in which they are applied.

Background/objective The dietary inflammatory index (DII) measured at one time point is associated with risk of several chronic diseases but disease risk may change with longitudinal changes in DII scores. Data are lacking regarding changes in DII scores over time, therefore we assessed changes in the DII in the Women's Health Initiative (WHI). Methods DII scores were calculated using data from repeated food frequency questionnaires in the WHI Observational Study (OS; n=76,671) at baseline and Year 3, and the WHI Dietary Modification trial (DM; n=48,482) at three time points. Lower DII scores represent more anti-inflammatory diets. We used generalized estimating equations to compare mean changes in DII over time, adjusting for multiple comparisons; and multivariable linear regression to determine predictors of DII change. Results In the OS, mean DII decreased modestly from −1.14 at baseline to −1.50 at Year 3. In the DM, DII was −1.32 in Year 1, −1.60 in Year 3, and −1.48 in Year 6 in the intervention arm, and was −0.65 in Year 1, −0.94 in Year 3 and −0.96 in Year 6 in the control arm. These changes were modified by BMI, education, and race/ethnicity. A prediction model explained 22% of the variance in the change in DII scores in the OS. Conclusion In this prospective investigation of postmenopausal women, reported dietary inflammatory potential decreased modestly over time. Largest reductions were observed in normal weight, highly educated women. Future research is warranted to examine whether reductions in DII are associated with decreased chronic disease risk.

e14078 Background: Traditional methods such as the 3+3 design developed in the 1940s continue to be used in the majority of early phase oncology studies. Researchers have found that the traditional methods identify the appropriate dose level only 30% of the time. Patients are also exposed to sub-therapeutic doses due to the conservative methods. With these limitations on traditional design options, innovative methods need to be developed, adopted and assessed. Methods: This quantitative study assessed the association of the design methods (adaptive versus traditional) used for early phase oncology studies (adaptive versus traditional) and the outcome of late stage clinical trials. Differences by cancer type and by drug classification were also assessed. A sample of studies for this analysis was extracted from the National Institute of Health Clinical registry and results database. The data used for the analysis was extracted by the Clinical Trials Transformation Initiative (CTTI) Aggregate Analysis of ClinicalTrials.gov (AACT). Results: When assessing study design and outcome, there were lower odds of a positive outcome when adaptive methods were used though this association was not statistically significant (OR [95% highest posterior density (HPD)]:0.66 [0.20, 1.21]). Among the different drug types, using adaptive compared to traditional methods was associated with significantly higher odds of a positive outcome for taxanes, OR: 2.75, 95% HPD: 1.01, 5.16) and other, OR: 3.23, 95% HPD: 1.58, 5.46) but no association among studies of monoclonal antibodies or protein kinase inhibitors. There were no significant associations between early phase study design and outcome in late phase studies by cancer type (lung, breast, other). Conclusions: While results associated with the use of adaptive methods were not significant, further research should be conducted using all completed oncology clinical trials in the database to more precisely determine the relationship between adaptive study design in early phase oncology studies and outcomes in late stage studies. In addition, improvements in traditional versus adaptive design capture in the ClinicalTrials.gov database needs to be considered.

e17561 Background: Prostate cancer (PCa) is common in countries with affluent dietary patterns and represents a heterogeneous collection of subtypes with varying behavior. Reductionist strategies focusing on individual nutrients or foods have not clearly defined risk factors. We have developed mechanisms-based dietary patterns focusing upon inflammation and chronic insulin hypersecretion, processes that are hypothesized to impact prostate carcinogenesis. Methods: First, we examined associations of the empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory pattern (EDIP) scores with circulating concentrations of relevant biomarkers, to assess the validity of these two dietary patterns. Secondly, we investigated associations of the EDIH and EDIP with risk of PCa (total, low-grade, high-grade, advanced and lethal). EDIH and EDIP dietary scores calculated from food frequency questionnaire data for 3,517 men and women who provided a blood sample at enrollment, were used to validate dietary patterns against known relevant biomarkers. A separate sample of 49,317 men was used to evaluate the associations of EDIH and EDIP with prostate cancer risk. We used multivariable-adjusted linear regression to compute the percent change and 95% confidence intervals (95%CI) in biomarker concentrations, and Cox regression to estimate hazard ratios (HR) and 95%CI for PCa risk; in dietary score quintiles, using the lowest quintile as reference. Results: Compared to the lowest quintile, participants in the highest EDIH quintile (most hyperinsulinemic diets) had significantly higher concentrations of C-peptide, insulin, CRP, and TNF-R2 and lower adiponectin. Those consuming the most pro-inflammatory diets (EDIP) had significantly higher concentrations of IL-6, TNF-R2, C-peptide and insulin with lower adiponectin. Men classified in EDIH quintile 5 compared to 1, were also at higher total PCa risk: HR, 1.11; 95%CI, 1.01, 1.23; P-trend = 0.03, especially high-grade cancer: HR, 1.18; 95%CI, 1.02, 1.37; P-trend = 0.06; whereas the EDIP was not associated with risk. Conclusions: EDIH and EDIP predicted concentrations of biomarkers relevant to the insulinemic and inflammatory potential of diet in PLCO. EDIH predicted future PCa risk and may suggest a dietary pattern for PCa prevention.

PURPOSE: Dietary factors may influence colorectal cancer (CRC) survival through effects on inflammation. We examined the association between post-CRC diagnosis inflammatory potential of diet and all-cause and cancer-specific mortality in the Women’s Health Initiative. METHODS: The study included 463 postmenopausal women who developed CRC during follow-up and completed a food frequency questionnaire (FFQ), on average 1.7 years after diagnosis. Women were followed from CRC diagnosis until death, censoring, or the end of follow up in October 2014. Energy-adjusted dietary inflammatory index (E-DII)® scores were calculated from the FFQ and dietary supplement inventory. Cox proportional hazards models were fitted to estimate multivariable-adjusted HRs and 95% confidence intervals (CI) for all-cause, total cancer, and CRC-specific mortality with the most pro-inflammatory E-DII scores (tertile 3) as referent. RESULTS: After a median 11.6 years of follow-up, 162 deaths occurred, including 77 from CRC. Lowest tertile (i.e., most anti-inflammatory) E-DII scores from diet plus supplements were associated with significantly lower all-cause mortality (HR(T1vsT3)=0.49; 95% CI=0.31–0.79) compared to the most pro-inflammatory E-DII tertile. Modest associations with total cancer mortality or CRC-specific mortality were observed, though 95%CIs included 1. CONCLUSIONS: Consuming a dietary pattern and supplements with more anti-inflammatory potential after CRC diagnosis may improve overall survival among postmenopausal women.

Background We examined the role of the insulinemic potential of diet and lifestyle in the development of cancers of the digestive system, using two plasma C-peptide-based indices: the empirical dietary index for hyperinsulinemia (EDIH) and empirical lifestyle index for hyperinsulinemia (ELIH). Methods We used Cox regression to analyze data on 45 816 men (Health Professionals Follow-up Study, 1986–2012) and 74 191 women (Nurses’ Health Study, 1984–2012) to examine associations between EDIH and ELIH scores and digestive system cancers. We computed the diet-only score (EDIH) from food-frequency questionnaires administered every 4 years. The lifestyle score (ELIH) included diet, body mass index, and physical activity. Outcomes included incident cancer of the digestive system (mouth, throat, esophagus, stomach, small intestine, and colorectum) and its accessory organs (pancreas, gallbladder, and liver). P values were two-sided. Results We found direct associations between higher insulinemic potential of diet or lifestyle and risk of developing digestive system cancers in both men and women. The pooled multivariable hazard ratios (HRs) for participants comparing the highest to lowest EDIH quintile were: HR = 1.27, 95% confidence interval (CI) = 1.15 to 1.40, Ptrend Conclusions The findings suggest that interventions to reduce the insulinemic potential of diet and lifestyle may be a means of preventing digestive system cancer.

OBJECTIVE: To investigate whether a dietary pattern derived using inflammatory biomarkers is associated with rheumatoid arthritis (RA) risk. METHODS: We prospectively followed 79,988 women in the Nurses’ Health Study (NHS, 1984–2014) and 93,572 women in the NHSII (1991–2013); incident RA was confirmed by medical records. Food frequency questionnaires (FFQ) were completed at baseline and approximately every 4 years. Inflammatory dietary pattern was assessed from FFQ data using the Empirical Dietary Inflammatory Pattern (EDIP), including 18 anti-/pro-inflammatory food/beverage groups weighted by correlations with plasma inflammatory biomarkers (interleukin-6, C-reactive protein, and tumor necrosis factor-α receptor 2). We investigated associations between EDIP and RA using Cox regression. RESULTS: We identified 1,185 incident RA cases over 4,425,434 person-years. EDIP was not associated with overall RA risk (p trend=0.21 across EDIP quartiles). Among women ≤55 years, increasing EDIP was associated with increased overall RA risk; HRs (95%CIs) across EDIP quartiles were: 1.00 (reference), 1.14 (0.86–1.51), 1.35 (1.03–1.77), and 1.38 (1.05–1.83; p for trend=0.01). Adjusting for BMI attenuated this association. Increasing EDIP was associated with increased seropositive RA risk among women ≤55 years (p for trend=0.04). There was no association between EDIP and RA among women >55 years (EDIP-age interaction: p=0.03). CONCLUSION: An inflammatory dietary pattern was associated with increased seropositive RA risk with onset ≤55 years old, and this association may be partially mediated through BMI.

BACKGROUND: The empirical dietary inflammatory pattern (EDIP) score has been associated with concentrations of circulating inflammatory biomarkers in European Americans. OBJECTIVE: 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. METHODS: 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. RESULTS: 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

Inflammation is a process central to carcinogenesis and in particular to colorectal cancer (CRC). Previously, we developed a dietary inflammatory index (DII) from extensive literature review to assess the inflammatory potential of diet. In the current study, we utilized this novel index in the Women's Health Initiative to prospectively evaluate its association with risk of CRC in postmenopausal women.The DII was calculated from baseline food frequency questionnaires administered to 152,536 women aged 50-79 years without CRC at baseline between 1993 and 1998 and followed through 30 September 2010. Incident CRC cases were ascertained through a central physician adjudication process. Multiple covariate-adjusted Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95 % confidence intervals (95 % CI) for colorectal, colon (proximal/distal locations), and rectal cancer risk, by DII quintiles (Q).During an average 11.3 years of follow-up, a total of 1,920 cases of CRC (1,559 colon and 361 rectal) were identified. Higher DII scores (representing a more pro-inflammatory diet) were associated with an increased incidence of CRC (HRQ5-Q1 1.22; 95 % CI 1.05, 1.43; p trend = 0.02) and colon cancer, specifically proximal colon cancer (HRQ5-Q1 1.35; 95 % CI 1.05, 1.67; p trend = 0.01) but not distal colon cancer (HRQ5-Q1 0.84; 95 % CI 0.61, 1.18; p trend = 0.63) or rectal cancer (HRQ5-Q1 1.20; 95 % CI 0.84, 1.72; p trend = 0.65).Consumption of pro-inflammatory diets is associated with an increased risk of CRC, especially cancers located in the proximal colon. The absence of a significant association for distal colon cancer and rectal cancer may be due to the small number of incident cases for these sites. Interventions that may reduce the inflammatory potential of the diet are warranted to test our findings, thus providing more information for colon cancer prevention.

Background: Two indexes exist to describe dietary inflammatory potential: an empirical dietary inflammatory pattern (EDIP) composed of food groups as reported on a food-frequency questionnaire (FFQ) and a literature-derived dietary inflammatory index (DII) composed mainly of nutrients.Objective: We compared the ability of the 2 indexes to predict concentrations of inflammatory markers and hypothesized that the EDIP would be more predictive because it was derived on the basis of circulating inflammatory markers.Methods: Both EDIP and DII scores were calculated from FFQ data reported by 5826 women in the Nurses' Health Study II and 5227 men in the Health Professionals Follow-Up Study. We used multivariable-adjusted linear regression analyses to calculate relative differences in concentrations of 4 plasma inflammatory markers-C-reactive protein (CRP; milligrams per liter), interleukin 6 (IL-6; picograms per milliliter), tumor necrosis factor α receptor 2 (TNFαR2; picograms per milliliter), and adiponectin (nanograms per milliliter)-in quintiles of the dietary indexes.Results: Spearman correlations between the EDIP and DII scores were modest (r = 0.29 and 0.21 for women and men, respectively; all P < 0.0001). Higher scores on both dietary indexes were associated with higher concentrations of inflammatory markers, although they were associated with lower adiponectin concentrations and there was no association between the DII and adiponectin in men. For example, percentage differences in concentrations of biomarkers in quintile 5 generally were higher (lower for adiponectin) than in quintile 1 (for the EDIP and DII, respectively-women: CRP, +60% and +49%; IL-6, +23% and +21%; TNFαR2, +7% and +4%; adiponectin, -21% and -14%; men: CRP, +38% and +29%; IL-6, +14% and +24%; TNFαR2, +9% and +5%; adiponectin, -16% and -4%.)Conclusion: Despite design differences, the EDIP and DII both assess dietary inflammatory potential in men and women, with the EDIP showing a greater ability to predict concentrations of plasma inflammatory markers.

Dietary assessment has long been known to be challenged by measurement error. A substantial amount of literature on methods for determining the effects of error on causal inference has accumulated over the past decades. These methods have unrealized potential for improving the validity of data collected for research studies and national nutritional surveillance, primarily through the NHANES. Recently, the validity of dietary data has been called into question. Arguments against using dietary data to assess diet–health relations or to inform the nutrition policy debate are subject to flaws that fall into 2 broad areas: 1) ignorance or misunderstanding of methodologic issues; and 2) faulty logic in drawing inferences. Nine specific issues are identified in these arguments, indicating insufficient grasp of the methods used for assessing diet and designing nutritional epidemiologic studies. These include a narrow operationalization of validity, failure to properly account for sources of error, and large, unsubstantiated jumps to policy implications. Recent attacks on the inadequacy of 24-h recall–derived data from the NHANES are uninformative regarding effects on estimating risk of health outcomes and on inferences to inform the diet-related health policy debate. Despite errors, for many purposes and in many contexts, these dietary data have proven to be useful in addressing important research and policy questions. Similarly, structured instruments, such as the food frequency questionnaire, which is the mainstay of epidemiologic literature, can provide useful data when errors are measured and considered in analyses.

The food-based empirical dietary index for hyperinsulinemia (EDIH) score assesses the insulinemic potential of diet. This cross-sectional study evaluated associations between EDIH scores from food frequency questionnaires with c-peptide concentrations and with 448 metabolites, from fasting plasma samples, in multivariable linear regression analyses. Metabolites were measured with liquid chromatography tandem mass spectroscopy. Using a robust two-stage study design, discovery of metabolite associations was conducted among 1109 Women&rsquo, s Health Initiative (WHI) Hormone Therapy (HT) trial participants and results replicated in an independent dataset of 810 WHI Observational Study (OS) participants. In both discovery and replication datasets, statistical significance was based on the false-discovery rate adjusted P &lt, 0.05. In the multivariable-adjusted analyses, EDIH was significantly associated with c-peptide concentrations among 919 women (HT &amp, OS) with c-peptide data. On average, c-peptide concentrations were 18% higher (95% CI, 6%, 32%, P-trend &lt, 0.0001) in EDIH quintile 5 compared to quintile 1. Twenty-six metabolites were significantly associated with EDIH in the discovery dataset, and 19 of these were replicated in the validation dataset. Nine metabolites were found to decrease in abundance with increasing EDIH scores and included: C14:0 CE, C16:1 CE, C18:1 CE, C18:3 CE, C20:3 CE, C20:5 CE, C36:1 PS plasmalogen, trigonelline, and eicosapentanoate, whereas the 10 metabolites observed to increase with increasing EDIH scores were: C18:2 SM, C36:3 DAG, C36:4 DAG-A, C51:3 TAG, C52:3 TAG, C52:4, TAG, C54:3 TAG, C54:4 TAG, C54:6 TAG, and C10:2 carnitine. Cholesteryl esters, phospholipids, acylglycerols, and acylcarnitines may constitute circulating metabolites that are associated with insulinemic dietary patterns.

We utilized the dietary inflammatory index (DII) to investigate associations between patterns of change in, and history of the inflammatory potential of diet and risk of breast cancer in the Women's Health Initiative (WHI). We included 70,998 postmenopausal women aged 50-79 years recruited from 1993 to 1998 into the WHI Observational Study and Dietary Modification trial control group and followed through August 29, 2014. We utilized data from food frequency questionnaires administered at baseline and Year 3, to calculate average DII scores, patterns of change in DII, and used these measures in multivariable-adjusted Cox regression models to estimate hazards ratios (HR) and 95% confidence intervals (CI) for incident invasive breast cancer and its subtypes. After 1,093,947 person-years of follow-up, 3471 cases of invasive breast cancer were identified. There was no substantial association between average DII scores or patterns of change in DII and risk of overall invasive breast cancer (HR, 1.03; 95% CI, 0.90, 1.17; P-trend=0.79; comparing extreme average DII quintiles). However, there was a significant nonlinear association between average DII scores and the ER-, PR-, HER2+, subtype (HR, 2.37; 95% CI, 1.08, 5.20; P-trend=0.18; comparing extreme quintiles). For patterns of change in DII, the age-adjusted association with ER-, PR-, HER2+ subtype comparing women in the proinflammatory stable to those in the anti-inflammatory stable categories (HR, 1.82; 95% CI, 1.06, 3.13) persisted in the multivariable-adjusted model but was less precise (HR, 1.85; 95% CI, 0.96, 3.55; P=0.06). Dietary inflammatory potential may differentially influence the development of specific breast cancer phenotypes.

Adherence to the 2007 WCRF/AICR cancer prevention recommendations has been associated with lower cancer risk but the underlying biological mechanisms have not been elucidated. We utilized dietary and lifestyle data from 11,342 women in the Nurses' Health Study and 8,136 men in the Health Professionals Follow-up Study, to investigate associations between adherence scores and markers of inflammation, hormonal and insulin response. Two scores ranging from 0 to 3 were constructed to assess adherence to the energy balance-related recommendations (weight management, physical activity, energy density); and the plant, animal foods and alcohol intake recommendations; with higher scores indicating greater adherence. The following biomarkers were assessed in plasma samples donated by chronic disease-free women (1990) and men (1994): C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α receptor 2 (TNFαR2) and adiponectin for inflammation; estrone and estradiol for hormonal response in women, C-peptide for hyperinsulinemia; and triglycerides/high density lipoprotein-cholesterol (TG/HDL) ratio for insulin resistance. In multivariable-adjusted linear regression analyses, we estimated relative concentrations of biomarkers across adherence categories. There was a significant trend of lower (higher for adiponectin) biomarker concentrations with higher adherence to the energy balance recommendations (all p trend0.0001). Comparing the highest (3) to the lowest recommendation category (0-1), the percent difference in relative concentrations of biomarkers was CRP, -69%; IL6, -41%; TNFαR2, -13%; adiponectin, +36%; C-peptide, -43%; TG/HDL, -43%; estrone, -31%; and estradiol, -43%; in women; and CRP, -59%; IL6, -42%; TNFαR2, -10%; adiponectin, +22%; C-peptide, -44%; and TG/HDL, -40%; in men. In contrast, associations between adherence to the plant, animal foods and alcohol intake recommendations and biomarker concentrations were weaker, and mostly nonsignificant. The healthier biomarker profile associated with greater adherence to the WCRF/AICR cancer prevention recommendations is driven mainly by adherence to the energy balance-related recommendations.

We examined the associations between changes in dietary inflammatory potential and risk of colorectal cancer (CRC) in 87,042 postmenopausal women recruited from 1993-1998 by the Women's Health Initiative, conducted in the United States. Food frequency questionnaire data were used to compute patterns of change in dietary inflammatory index (DII) scores and cumulative average DII scores over 3 years. Cox regression models were used to estimate hazard ratios for CRC risk. After a median of 16.2 years of follow-up, 1,038 CRC cases were diagnosed. DII changes were not substantially associated with overall CRC, but proximal colon cancer risk was higher in the proinflammatory-change DII group than in the antiinflammatory-stable DII group (hazard ratio = 1.32, 95% confidence interval: 1.01, 1.74). Among nonusers of nonsteroidal antiinflammatory drugs (NSAIDs) (Pinteraction = 0.055), the proinflammatory-stable DII group was at increased risk of overall CRC and proximal colon cancer. Also among nonusers of NSAIDs, risks of overall CRC, colon cancer, and proximal colon cancer were higher in the highest quintile compared with the lowest cumulative average DII quintile (65%, 61%, and 91% higher risk, respectively). Dietary changes toward, or a history of, proinflammatory diets are associated with an elevated risk of colon cancer, particularly for proximal colon cancer and among nonusers of NSAIDs.

Purpose. We combined data from the National Breast and Cervical Cancer Early Detection (NBCCEDP) and Well-Integrated Screening and Evaluation for Women Across the Nation (WISEWOMAN) programs in South Carolina to assess whether cancer screening outcomes in NBCCEDP impacted participation in WISEWOMAN lifestyle interventions, and whether the status of WISEWOMAN baseline risk factors (obesity, diabetes, hypercholesterolemia, hypertension, and smoking) determined subsequent completion of lifestyle interventions. Design. Case-control. Setting. Three WISEWOMAN implementation sites in South Carolina. Subjects. The study comprised 7841 NBCCDEP participants in three WISEWOMAN program sites. The two programs serve financially disadvantaged women. Measures. Outcome measures were participation in WISEWOMAN lifestyle interventions and completion of lifestyle interventions. The main predictor measures were cancer screening outcomes and baseline chronic disease risk factors. Covariate measures included age, race, body mass index, smoking status, and education. Analysis. We used multivariable logistic regression models to examine the odds of participation in and completion of WISEWOMAN lifestyle interventions. Results. The association between cancer screening outcome and participation in WISEWOMAN lifestyle interventions among NBCCEDP participants differed significantly by education and smoking status. Among smokers or highly educated women, having an outcome of cancer or precancerous lesion through the NBCCEDP screening compared to normal screening outcomes was significantly associated with participation in lifestyle interventions, with odds ratios of 2.69 (95% confidence interval [CI], 1.10–6.58) for highly educated women and 1.82 (95% CI, 1.00–3.31) for smokers. Similarly, smokers or diabetics were more likely than nonsmokers or nondiabetics, respectively, to complete lifestyle interventions. Conclusion. Nonsmokers and women with lower education in NBCCEDP may need additional navigation to lifestyle interventions in an integrated program implementation approach to improve participation in and completion of WISEWOMAN interventions.

Purpose. To examine the associations among intake of refined grains, whole grains and dietary fiber and aggressiveness of prostate cancer in African Americans (AA,n=930) and European Americans (EA,n=993) in a population-based, case-only study (The North Carolina-Louisiana Prostate Cancer Project, PCaP).Methods. Prostate cancer aggressiveness was categorized as high, intermediate or low based on Gleason grade, PSA level and clinical stage. Dietary intake was assessed utilizing the NCI Diet History Questionnaire. Logistic regression (comparing high to intermediate/low aggressive cancers) and polytomous regression with adjustment for potential confounders were used to determine odds of high prostate cancer aggressiveness with intake of refined grains, whole grains and dietary fiber from all sources.Results. An inverse association with aggressive prostate cancer was observed in the 2nd and 3rd tertiles of total fiber intake (OR = 0.70; 95% CI, 0.50–0.97 and OR = 0.61; 95% CI, 0.40–0.93, resp.) as compared to the lowest tertile of intake. In the race-stratified analyses, inverse associations were observed in the 3rd tertile of total fiber intake for EA (OR = 0.44; 95% CI, 0.23–0.87) and the 2nd tertile of intake for AA (OR = 0.57; 95% CI, 0.35–0.95).Conclusions. Dietary fiber intake was inversely associated with aggressive prostate cancer among both AA and EA men.

Background & Aims Specific nutritional components are likely to induce intestinal inflammation, which is characterized by increased levels of interleukin 6 (IL6), C-reactive protein (CRP), and tumor necrosis factor–receptor superfamily member 1B (TNFRSF1B) in the circulation and promotes colorectal carcinogenesis. The inflammatory effects of a diet can be estimated based on an empiric dietary inflammatory pattern (EDIP) score, calculated based on intake of 18 foods associated with plasma levels of IL6, CRP, and TNFRSF1B. An inflammatory environment in the colon (based on increased levels of IL6, CRP, and TNFRSF1B in peripheral blood) contributes to impairment of the mucosal barrier and altered immune cell responses, affecting the composition of the intestinal microbiota. Colonization by Fusobacterium nucleatum has been associated with the presence and features of colorectal adenocarcinoma. We investigated the association between diets that promote inflammation (based on EDIP score) and colorectal cancer subtypes classified by level of F nucleatum in the tumor microenvironment. Methods We calculated EDIP scores based on answers to food frequency questionnaires collected from participants in the Nurses' Health Study (through June 1, 2012) and the Health Professionals Follow-up Study (through January 31, 2012). Participants in both cohorts reported diagnoses of rectal or colon cancer in biennial questionnaires; deaths from unreported colorectal cancer cases were identified through the National Death Index and next of kin. Colorectal tumor tissues were collected from hospitals where the patients underwent tumor resection and F nucleatum DNA was quantified by a polymerase chain reaction assay. We used multivariable duplication-method Cox proportional hazard regression to assess the associations of EDIP scores with risks of colorectal cancer subclassified by F nucleatum status. Results During 28 years of follow-up evaluation of 124,433 participants, we documented 951 incident cases of colorectal carcinoma with tissue F nucleatum data. Higher EDIP scores were associated with increased risk of F nucleatum–positive colorectal tumors (Ptrend = .03); for subjects in the highest vs lowest EDIP score tertiles, the hazard ratio for F nucleatum–positive colorectal tumors was 1.63 (95% CI, 1.03–2.58). EDIP scores did not associate with F nucleatum–negative tumors (Ptrend = .44). High EDIP scores associated with proximal F nucleatum–positive colorectal tumors but not with proximal F nucleatum–negative colorectal tumors (Pheterogeneity = .003). Conclusions Diets that may promote intestinal inflammation, based on EDIP score, are associated with increased risk of F nucleatum–positive colorectal carcinomas, but not carcinomas that do not contain these bacteria. These findings indicate that diet-induced intestinal inflammation alters the gut microbiome to contribute to colorectal carcinogenesis; nutritional interventions might be used in precision medicine and cancer prevention.

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.

Importance Inflammation is important in colorectal cancer development. Diet modulates inflammation and may thus be a crucial modifiable factor in colorectal cancer prevention. Objective To 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 Participants Cohort 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. Exposures EDIP scores calculated from food frequency questionnaires administered every 4 years. Main Outcomes and Measures Incident colorectal cancer. Results We 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 P = .007 for trend), and 32% (men and women: pooled HR, 1.32; 95% CI, 1.12-1.55; P 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 Relevance Findings 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.

Background & Aims 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. Methods 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). Results 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 ( P trend = .02), and varied with degree of peritumoral lymphocytic reaction ( P heterogeneity P trend P trend > .80). Conclusions 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.

Background: Specific foods and nutrients, including alcohol, may contribute to gut barrier dysfunction. However, to our knowledge, the influence of whole diets is currently unknown. Objective: We aimed to cross-sectionally investigate associations of dietary patterns with plasma soluble CD14 (sCD14), which is released by macrophages on stimulation with endotoxin and has been used as a marker of gut hyperpermeability. Methods: We used food-frequency questionnaire data collected from 689 women in the Nurses’ Health Study and 509 men in the Health Professionals Follow-Up Study. Our principal component analysis identified 2 dietary patterns: “Western” (higher intakes of red meat, processed meat, desserts, and refined grains) and “prudent” (higher intakes of fruits, vegetables, fish, and whole grains). In multivariable-adjusted logistic regression analyses, we estimated ORs and 95% CIs for high (equal to or greater than the median compared with less than the median) sCD14 concentrations in quintiles of each dietary pattern. Using logistic regression, we also investigated the joint association of the Western dietary pattern and alcohol intake or C-reactive protein (CRP) with sCD14 concentrations. Results: Western dietary pattern scores were positively associated with sCD14 concentrations (OR: 1.86; 95% CI: 1.24, 2.79; P -trend = 0.0005; comparing extreme quintiles). Analyses of joint associations suggested that the strongest associations with higher sCD14 concentrations were for persons with both high Western pattern scores and high alcohol intake compared with participants with low scores for both (OR: 2.96; 95% CI: 1.61, 5.45) or for participants with both high Western pattern scores and high CRP values compared with those with low scores for both (OR: 4.11; 95% CI: 2.57, 6.58). The prudent pattern was not associated with sCD14 concentrations. Conclusions: Higher consumption of the Western dietary pattern is associated with a marker of macrophage activation and gut hyperpermeability, especially when coupled with high alcohol intake and heightened systemic inflammation. Our findings need confirmation in studies with additional markers of gut barrier dysfunction.

© 2015 Elsevier Inc.. Purpose: Many dietary factors have either proinflammatory or anti-inflammatory properties. We previously developed a dietary inflammatory index (DII) to assess the inflammatory potential of diet. In this study, we conducted a construct validation of the DII based on data from a food frequency questionnaire and three inflammatory biomarkers in a subsample of 2567 postmenopausal women in the Women's Health Initiative Observational Study. Methods: We used multiple linear and logistic regression models, controlling for potential confounders, to test whether baseline DII predicted concentrations of interleukin-6, high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor alpha receptor 2, or an overall biomarker score combining all three inflammatory biomarkers. Results: The DII was associated with the four biomarkers with beta estimates (95% confidence interval) comparing the highest with lowest DII quintiles as follows: interleukin-6: 1.26 (1.15-1.38), Ptrend< .0001; tumor necrosis factor alpha receptor 2: 81.43 (19.15-143.71), Ptrend=.004; dichotomized hs-CRP (odds ratio for higher vs. lower hs-CRP): 1.30 (0.97-1.67), Ptrend=.34; and the combined inflammatory biomarker score: 0.26 (0.12-0.40), Ptrend=.0001. Conclusions: The DII was significantly associated with inflammatory biomarkers. Construct validity of the DII indicates its utility for assessing the inflammatory potential of diet and for expanding its use to include associations with common chronic diseases in future studies.

Objective: We examined the association between the dietary inflammatory index (DII) and risk of invasive breast cancer (BC) incidence and mortality in postmenopausal women. Methods: The DII was calculated from a baseline food frequency questionnaire administered to 117,510 women at risk of BC in the Women's Health Initiative (WHI) Observational Study and Clinical Trials, among whom 5,889 later developed BC and 406 died during an average of 12.3 years follow-up. We used Cox regression to estimate hazard ratios and 95% CI by DII tertiles for invasive BC and its subtypes, and for BC mortality. The lowest tertile (representing the most anti-inflammatory diet) was the referent. Results: The DII was not associated with incident BC overall, but was positively associated with risk of HER2+ BC (HRT3vsT1, 1.31; 95%CI, 1.06, 1.61;Ptrend=0.01). We observed a higher risk for BC mortality with intake of more pro-inflammatory diets, controlling for age and total energy intake (HRT3vsT1, 1.48; 95%CI, 1.15, 1.91;Ptrend, 0...

Background: Inflammation regulates key biologic processes in chronic disease and can be modulated by diet. Our objective was to use the dietary inflammatory index (DII), a novel tool to characterize the inflammatory potential of diet, to examine how post-cancer diagnosis dietary quality is associated with overall survival in the Women's Health Initiative (WHI) Observational Study (OS) and Dietary Modification Trial (DM). Methods: After excluding baseline cancers and energy outliers, the analytical cohort had 4,241 postmenopausal women (19% of total cancer cases), aged 50 to 79 years at baseline, in the WHI OS ( n = 1,852) and DM ( n = 2,389), who developed invasive cancer during follow-up and completed a food frequency questionnaire after diagnosis. These women were followed from dietary assessment until death from any cause. Energy-adjusted DII scores from food only and from food plus supplement (any reported dietary supplement related to DII parameters) after cancer diagnosis for each subject were calculated by multiplying the inflammatory effect scores determined based on extensive literature review and intake values for each food parameter, and then summing across all the food parameters. Death was ascertained by clinical center follow-up or by searching the National Death Index with central or local adjudication. Cox proportional hazards models were fit to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for all-cause mortality comparing women in higher DII quartiles with those in the first quartile. Results: After a median 11.2 years of follow-up, 1,470 deaths occurred. After adjustment for key covariates, women who consumed a more pro-inflammatory diet (in higher quartiles of DII score from food only) after a cancer diagnosis had a significantly higher risk of death from any cause compared to women consuming a more anti- inflammatory diet (HR Q4:Q1 = 1.18; 95% CI, 1.01–1.38; P trend = 0.015). In analyses using DII score from both diet and supplements, a pro-inflammatory DII score was associated with even higher risk of all-cause mortality (HRQ4:Q1 = 1.63; 95% CI, 1.40–1.91; P trend < 0.0001). Conclusions: Consuming a more pro-inflammatory diet after cancer diagnosis was associated with increased risk of death from any cause. The following are the 17 highest-scoring abstracts of those submitted for presentation at the 40th Annual ASPO meeting held March 13–15, 2016, in Columbus, OH.

In a Columbia, South Carolina-based case–control study, we developed a healthy lifestyle index from five modifiable lifestyle factors (smoking, alcohol intake, physical activity, diet, and body mass index), and examined the association between this lifestyle index and the risk of colorectal adenomatous polyps (adenoma). Participants were recruited from a local endoscopy center and completed questionnaires related to lifestyle behaviors prior to colonoscopy. We scored responses on each of five lifestyle factors as unhealthy (0 point) or healthy (1 point) based on current evidence and recommendations. We added the five scores to produce a combined lifestyle index for each participant ranging from 0 (least healthy) to 5 (healthiest), which was dichotomized into unhealthy (0–2) and healthy (3–5) lifestyle scores. We used logistic regression to calculate odds ratios (OR) and 95 % confidence intervals (CI) for adenoma with adjustment for multiple covariates. We identified 47 adenoma cases and 91 controls. In the main analyses, there was a statistically nonsignificant inverse association between the dichotomous (OR 0.54; 95 % CI 0.22, 1.29) and continuous (OR 0.75; 95 % CI 0.51, 1.10) lifestyle index and adenoma. Odds of adenoma were significantly modified by the use of non-steroidal anti-inflammatory drugs (NSAIDs) (p interaction = 0.04). For participants who reported no use of NSAIDs, those in the healthy lifestyle category had a 72 % lower odds of adenoma as compared to those in the unhealthy category (OR 0.28; 95 % CI 0.08, 0.98), whereas a one-unit increase in the index significantly reduced odds of adenoma by 53 % (OR 0.47; 95 % CI 0.26, 0.88). Although these findings should be interpreted cautiously given our small sample size, our results suggest that higher scores from this index are associated with reduced odds of adenomas, especially in non-users of NSAIDs. Lifestyle interventions are required to test this approach as a strategy to prevent colorectal adenomatous polyps.

The role of diet in modifying chronic disease risk through its potential effect on inflammation is of great interest. We assessed changes over time in the inflammatory potential of specific dietary...

ObjectiveTo perform construct validation of the population-based Dietary Inflammatory Index (DII) using dietary data from two different dietary assessments and serum high-sensitivity C-reactive protein (hs-CRP) as the construct validator.DesignUsing data derived from (i) three 24 h dietary recalls (24HR) at baseline and at the end of each subsequent quarter (i.e. up to fifteen over a year) and (ii) a 7 d dietary recall (7DDR) measured at baseline and then quarterly, regression analyses were conducted to test the effect of the DII score on serum hs-CRP as dichotomous (≤3 mg/l, >3 mg/l), while controlling for important potential confounders.SettingExisting data from the Seasonal Variation of Blood Cholesterol Study (SEASONS), a longitudinal observational study of healthy participants recruited in Worcester, MA, USA and participants were followed for 1 year.SubjectsParticipants who had at least one hs-CRP measurement over her/his 1-year participation (n495 for 24HR,n559 for 7DDR).ResultsHigher DII scores were associated with values of hs-CRP >3 mg/l (OR = 1·08; 95 % CI 1·01, 1·16,P= 0·035 for the 24HR; and OR = 1·10; 95 % CI 1·02, 1·19,P= 0·015 for the 7DDR).ConclusionsThe population-based DII was associated with interval changes in hs-CRP using both the 24HR and 7DDR. The success of this first-of-a-kind attempt at relating individuals’ intakes of inflammation-modulating foods using this refined DII, and the finding that there is virtually no drop-off in predictive capability using a structured questionnaire in comparison to the 24HR standard, sets the stage for use of the DII in a wide variety of other epidemiological and clinical studies.

Background: Experimental and ecological studies support links between vitamin D and prostate cancer prevention and prognosis. Given the lower levels of circulating 25-hydroxyvitamin D [25(OH)D] and higher prostate cancer incidence and mortality among African Americans compared to other racial/ethnic groups, the aim of this investigation was to examine the relationship between plasma 25(OH)D levels and prostate cancer aggressiveness among African and European Americans. Methods: Plasma 25(OH)D was measured using LC/MS/MS in 537 African Americans and 663 European Americans with newly-diagnosed prostate cancer from PCaP. Men were classified as cases (high aggressiveness) if Gleason sum ≥8, or PSA >20 ng/ml, or Gleason sum ≥7 AND clinical stage = T3c-T4c, or Gleason sum=7 with primary pattern 4. The comparison group (low aggressiveness) included men with Gleason sum Results: African Americans had significantly lower mean concentrations of 25(OH)D (17.7 ± 7.6 ng/ml) compared to European Americans (24.6 ± 9.6 ng/ml). The highest tertile (mean=25.79 ng/ml & median=24.29 ng/ml) and middle tertile (mean=16.09 ng/ml & median=15.83) of plasma 25(OH)D were positively associated with highly aggressive prostate cancer among African Americans after adjustment for age, season, education, physical activity, smoking status, and PSA screening history (OR=1.7, 95% CI=1.0, 2.8 and OR=1.8, 95%CI=1.1, 3.0, respectively). No significant associations were observed for European American men. Conclusions: Plasma 25(OH)D was positively associated with prostate cancer aggressiveness among African Americans but not European Americans, such that subjects with highly aggressive prostate cancer had increased odds of having higher plasma 25(OH)D levels. Research samples were collected after diagnosis, so effects of treatment, extent of disease or associated processes (e.g. weight loss) on plasma 25(OH)D may explain the findings. Ongoing studies include analysis of vitamin D binding protein (DBP) in the plasma and genotyping of DBP affinity variants in PCaP subjects. This approach may help explain the racial differences found, since DBP may modulate the impact of vitamin D status on prostate cancer. Citation Format: Anna Woloszynska-Read, Lenore Arab, John Adams, Jeannette T. Bensen, Elizabeth TH Fontham, James L. Mohler, Joseph Su, Fred Tabung, Hongmei Zhang, Donald L. Trump, Candace S. Johnson, Susan E. Steck. Plasma 25-hydroxyvitamin D levels are associated with aggressive prostate cancer among African Americans in the North Carolina-Louisiana Prostate Cancer Project (PCaP). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-12. doi:10.1158/1538-7445.AM2013-LB-12