Hypertension is a major public health challenge globally and in Iran. Given the role of inflammation in hypertension development, this study aimed to examine the association between the inflammatory potential of diet, quantified using the energy-adjusted Dietary Inflammatory Index (E-DII™), and the incidence of hypertension. The data of the present study were extracted from the Fasa Adult Cohort Study database. In this prospective cohort study, 10,138 participants were recruited at the baseline phase. Participants were contacted by telephone at regular intervals over 7 years. A selected group was also revisited after 5 years. Survival analysis was conducted to investigate the association between E-DII and hypertension incidence over a 7-year follow-up period, using Cox regression. Participants in the highest E-DII tertile (most pro-inflammatory diet) had a significantly higher risk for hypertension incidence during 7 years (HRT3 vs. T1 = 2.24, P value < 0.001). Moreover, the association of E-DII with hypertension incidence after 5 years was examined using logistic regression. Logistic regression revealed a significantly higher hypertension incidence after 5 years among participants in the highest E-DII tertile (ORT3 vs. T1 = 2.62, P value < 0.001). Linear regression showed positive and significant associations between E-DII and change in blood pressure components over 5 years. However, the associations in all models were attenuated and became statistically insignificant after adjustment for body mass index. Our findings indicate that consuming a pro-inflammatory diet was associated with an increased risk of developing hypertension. Moreover, body mass index emerged as a key covariate in this relationship.

Background:Heavy metals, like lead, arsenic, and cadmium, are linked to increased inflammation even in early life; however, anti-inflammatory diets may offset these effects. Methods:We evaluated associations between heavy metals and inflammatory biomarkers, and potential effect modification by diet in 399 adolescents aged 10 to 18 at baseline who attended two study visits 2 years apart (773 observations). At baseline, blood lead, urinary arsenic, and cadmium concentrations were measured, and the Children's Dietary Inflammatory Index (C-DII) was calculated. Fasting serum interleukin (IL)-4, IL-10, IL-1β, IL-6, IL-8, high-sensitivity C-reactive protein, and tumor necrosis factor-alpha were measured for both visits. Generalized estimating equation models were fit to assess associations between metal concentrations and repeatedly measured inflammatory biomarkers, adjusting for study visit and baseline sociodemographic and lifestyle variables. Effect modification by diet was assessed by including metal and C-DII tertiles interaction terms. Results:At baseline, the median age was 13.6 years, 50.4% were females, and 51.1% had a low socioeconomic status. Overall, there were no associations between metals and inflammatory markers in the entire population. In the most anti-inflammatory diet group (C-DII T1), higher blood lead was associated with higher IL-4, IL-1β, IL-6, and IL-8 levels, whereas for the most pro-inflammatory diet (C-DII T3), these associations were inverse (P-trend <0.05). Contrarily, higher urinary arsenic was associated with lower IL-4, IL-6, and IL-8 levels in the anti-inflammatory diet group and positively associated with these cytokines in the pro-inflammatory diet group (P-trend <0.05). Conclusion:Anti-inflammatory diets may modify adolescents' inflammatory response to lead and arsenic. Heavy metal toxicity mitigation by anti-inflammatory diets requires further research.

Breast cancer survivorship is frequently accompanied by impaired quality of life (QoL). Diet-related systemic inflammation may influence physical, emotional, and psychological well-being, yet evidence linking the inflammatory potential of diet to QoL in women with breast cancer remains limited. In this cross-sectional study, 600 women with confirmed breast cancer were recruited from the Isfahan Breast Cancer Registry between 2021 and 2023. Dietary intake and lifestyle characteristics were collected through structured telephone interviews. The Dietary Inflammatory Index (DII®) and energy-adjusted DII (E-DII™) were calculated, and QoL was assessed using a five-point Likert scale. Associations of DII and E-DII with QoL were examined using multivariable linear regression with adjustment for potential confounders. Quartile-based analyses and tests for linear trend were also performed. Higher DII scores were associated with lower QoL in adjusted models (β = −0.12; 95

Background: The Dietary Inflammatory Index (DII®) is a commonly used tool to assess diet-related inflammation. Higher DII scores have been associated with increased cardiovascular disease risk in observational studies. However, evidence examining cardiovascular outcomes across DII levels in controlled settings remains limited. This secondary analysis examined cross-sectional differences and longitudinal associations between dietary inflammatory potential and cardiovascular outcomes in healthy Australian adults. Methods: This study used data from a double-blind randomised crossover trial, in which 50 participants consumed 60 mL/day of either extra virgin high-polyphenol olive oil (HPOO; 320 mg/kg) or low-polyphenol olive oil (LPOO; 86 mg/kg) across two 3-week intervention periods, separated by a 2-week washout. Anthropometric measures (weight, height, waist circumference, and BMI) and cardiovascular outcomes (i.e., blood pressure, lipids, oxidised LDL, and HDL cholesterol efflux capacity) were assessed at four timepoints. DII and energy-adjusted DII (E-DIITM) scores were derived from 3-day food diaries. Linear mixed-effects models were used to compare cardiovascular outcomes across repeated-measures DII tertiles (low, medium, and high), adjusting for intervention, period, sequence, age, sex and waist circumference. Results: Forty-three participants completed this study. At baseline, BMI, waist circumference, systolic blood pressure, total cholesterol, and LDL differed significantly across DII tertiles (p < 0.05). However, over time, cardiovascular outcomes did not differ between medium or high versus low DII tertiles, and no significant time-by-tertile interactions were observed (all p > 0.05). DII values remained stable, while E-DII showed modest within-person reductions during both intervention periods (mean reduction: 0.886 units vs. 0.596 units). Conclusions: In this healthy cohort, there was no evidence of a consistent association between DII and short-term differences in cardiovascular outcomes across the intervention period. These findings should be interpreted cautiously, given the observational nature of DII groupings. Longer-duration studies with greater variation in dietary inflammatory potential are warranted to clarify the relationship between DII and cardiovascular health.

Background Walnuts may lower diet-related inflammation by providing anti-inflammatory compounds and displacing pro-inflammatory nutrients. Objective To explore the association between daily walnut consumption or abstention for 2 years and the Dietary Inflammatory Index (DII®). Design The Walnuts and Healthy Aging (WAHA) study is a dual-center (Loma Linda, California, USA and Barcelona, Spain), randomized trial, comparing a walnut-rich diet with a control diet over 2 years between May 2012 to May 2016, for age-related outcomes in healthy, free-living older adults aged 63-79 y. This ancillary study concerned only the Loma Linda cohort. Participants/setting A total of 319 older adults (mean age 69 y, 66% women) from Loma Linda, Ca were randomly assigned to walnut (n = 166) or control (n = 153) diets. Intervention The walnut group consumed 1-2 oz walnuts/day (30-60 g/day, ∼15% of energy), while the control group abstained from walnuts and limited other nuts to <2 servings/week. Both groups followed their usual background diet. Main outcome measures DII scores were calculated from five 24-hour dietary recalls taken at random during the 2-year period. Statistical analyses performed Linear mixed models tested DII differences between the walnut and control groups, adjusting for sex, age, BMI, race, energy intake, smoking status, physical activity, and educational attainment. Results The mean DII (SE) score was -0.025 (0.14) in the walnut group and 0.615 (0.14) in the control diet group (p<0.01). At the nutrient level, n-3 PUFAs (ß=-0.291; 95%CI: -0.450, -0.132; p<0.01), magnesium (ß=-0.014; 95%CI: -0.015, -0.013; p<0.01), carbohydrate (ß=-0.009; 95%CI: -0.014, -0.005; p<0.01), fiber (ß=-0.120; 95%CI: -0.133, -0.106; p=0.05), and protein (ß=-0.020; 95% CI: -0.031, -0.008; p<0.01), were associated with a more anti-inflammatory DII score, while intake of total and saturated fat were associated with a higher, more proinflammatory, DII score (ß=0.033; 95%CI: 0.020, 0.045; p<0.01 and ß=0.102; 95%CI: 0.080, 0.125; p<0.01 respectively). Conclusion Incorporating walnuts into the habitual diet was associated with more anti-inflammatory DII scores compared with a walnut-free control diet. These findings suggest that adding a single whole food may be a feasible complementary strategy for favorably improving the inflammatory potential of a diet.

Background: Breast cancer (BC) is responsible for a high proportion of cancer-related morbidity and mortality. A varied diet may play a role in the onset of BC. Objectives: We aimed to investigate the association between dietary diversity and BC risk. Methods: This population-based case-control study was conducted between May 2021 and October 2023, comprising 600 incident BC cases and 600 general population controls. We employed a valid and reliable 168-item food frequency questionnaire, with data collected one year prior to the date of diagnosis for cases and within the past year for controls. A dietary diversity score (DDS), focusing on consuming a variety of 5 food groups, with attainable scores between 0 and 10, was created as an indicator of total nutritional quality. Potential confounders were also assessed, including educational year, menopause, age at menarche, family socioeconomic status during adolescence, multivitamin intake, and benign breast diseases. We employed logistic regression models to estimate crude and adjusted odds ratios (ORs), controlled for potential confounders, to estimate the effect of DDS on BC risk. Results: DDS was associated with BC odds when analyzed as both a continuous and a categorical variable. The OR for DDS as a continuous variable was 0.90 [95% confidence interval (CI): 0.82, 0.99]. For participants with a DDS between 2.5 and 6, the OR was 0.58 (95% CI: 0.36, 0.95), and for those with a DDS >6, the OR was 0.41 (95% CI: 0.23, 0.73). A clear dose-response association was also observed [test for trend: OR= 0.66 (0.49, 0.86)]. Conclusions: We identified DDS, a measure of a balanced diet, as a novel protective factor for BC. Given the global increase in BC morbidity and mortality, this finding underscores the need for public health interventions and educational programs targeting diverse and balanced dietary patterns.

Introduction:Breast cancer remains a major cause of mortality among women in sub-Saharan Africa driven, in part, by low screening coverage. We assessed the prevalence and determinants of clinical breast examination (CBE) uptake among reproductive-aged women in Zambia. Methods:This cross-sectional study utilized data from 13,876 women aged 15-49 years who participated in the 2024 Zambia Demographic and Health Survey (ZDHS). The outcome variable was derived from participants' response to 'ever having had a breast examination by a health care provider.' Descriptive statistics and survey-weighted logistic regression analyses were conducted in Stata, with all estimates adjusted to account for the complex survey design used in the ZDHS. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were reported. Results:Overall, 13.3% (n = 1,845) of women reported ever receiving CBE. Among those screened, the majority were aged 30-39 years (35.4%), resided in urban areas (56.5%), had secondary level education (42.7%) and belonged to the richest wealth quintile (30.5%). Furthermore, only 17.8% of screened women had health insurance, and two-thirds (66.2%) had previously undergone cervical cancer screening. Higher education (AOR = 1.58; 95% CI: 1.08-2.32) and health insurance coverage (AOR = 1.30; 95% CI: 1.04-1.62) were positively associated with CBE uptake. Women who had visited a health facility in the previous 12 months (AOR = 1.38; 95% CI: 1.18-1.61) and those ever screened for cervical cancer (AOR = 5.95; 95% CI: 5.18-6.84) had significantly greater odds of receiving CBE, while women living with HIV were less likely to be screened (AOR = 0.82; 95% CI: 0.69-0.98). Regional variation was observed with women in Central (AOR = 1.43; 95% CI: 1.10-1.88), Copperbelt (AOR = 1.42; 95% CI: 1.12-1.78), Luapula (AOR = 1.94; 95% CI: 1.39-2.72), and Northwestern (AOR = 1.33; 95% CI: 1.01-1.77) provinces having higher odds of CBE compared with those in Lusaka, while women in Eastern Province were less likely to receive CBE (AOR = 0.68; 95% CI: 0.49-0.95). Conclusion:There is low utilization of CBE services among women aged 15-49 years in Zambia. Strategies which expand access and utilization of breast cancer screening services are warranted.

BACKGROUND AND AIMS:Systemic inflammation is an independent predictor of cardiovascular events, and nut-enriched diets are often recommended after acute myocardial infarction (AMI). However, the effects of mixed nuts on inflammatory biomarkers in secondary prevention remain unclear. This study evaluated the impact of incorporating mixed nuts into the Brazilian Cardioprotective Diet (DICA Br) on systemic inflammation and dietary inflammatory potential in post-AMI patients. METHODS AND RESULTS:This secondary analysis of the DICA-NUTS randomized controlled trial included 170 adults post-AMI, assigned to receive either the DICA Br diet alone (n = 85) or the same diet supplemented with 30 g/day of mixed nuts (10 g each of peanuts, cashews, and Brazil nuts; n = 85) for 16 weeks. Plasma concentrations of interleukins (IL-2, IL-4, IL-6, IL-10), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and C-reactive protein (CRP) were measured at baseline and post-intervention. Dietary inflammatory potential was assessed using the Dietary Inflammatory Index (DII®) and the energy-adjusted DII (E-DII™). No significant between-group differences were observed for any inflammatory biomarker or for DII and E-DII scores. Within the DICA group, IL-4 levels decreased (-4.56 pg/mL; 95% CI -9.00 to -0.11; p = 0.045), with a concurrent increase in the IFN-γ/IL-4 ratio (0.035; 95% CI 0.003 to 0.067; p = 0.04). IFN-γ concentrations were higher in the lowest DII tertile (p = 0.046) and inversely correlated with DII scores (ρ = -0.15; p = 0.006). CONCLUSION:Supplementation with 30 g/day of mixed nuts did not significantly modify inflammatory biomarkers or improve the anti-inflammatory potential of the diet over 16 weeks in post-AMI patients. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT03728127.

Evidence suggests that diet is associated with low-grade inflammation. The Dietary Inflammatory Index (DII) assesses the inflammatory potential of a diet; however, few studies have examined its association with hs-CRP and cytokines (IL-1β, IL-6, IL-8, IL-10, IL-12p70, and TNF-α) in Brazilian adults. This cross-sectional study, using data from 958 adults from the Viçosa Health and Nutrition Study (2012-2014), who were selected by two-stage probabilistic sampling. Dietary intake was assessed using a validated Food Frequency Questionnaire. DII scores were calculated, as were the energy-adjusted (E-DII) and residual-adjusted (E-DIIr) forms based on 25 dietary components. Inflammatory biomarkers were measured using high-sensitivity immunoturbidimetry and bead-based flow cytometry for cytokines. Linear and logistic regression models, adjusted for complex sampling design and covariates defined by a Directed Acyclic Graph (DAG), were tested in three hierarchical blocks (Stata 14.2; p < 0.05). Diets with higher inflammatory potential (E-DII, E-DIIr) were positively associated with log-transformed hs-CRP concentrations in adjusted models. In quartile analyses, individuals in the most pro-inflammatory quartile (DII, E-DII, E-DIIr) had higher hs-CRP concentrations. Logistic models showed no association between continuous scores and odds of hs-CRP ≥ 3 mg/L. However, significant associations emerged in the upper quartiles of the DII and E-DIIr. For IL-8, inverse associations appeared in both linear (DII, E-DIIr) and ordinal logistic regression (DII, E-DIIr). Findings support the association between pro-inflammatory diets and hs-CRP concentrations, with no consistent results for other cytokines. The DII may capture subclinical inflammation, but its utility could depend on methodology and timing, underscoring the need for standardized longitudinal studies.

PURPOSE:To evaluate: whether self-reported urinary tract stones (UTS) are associated with incident hypertension in postmenopausal women in the Women's Health Initiative; potential effect modification by diet-related inflammation and lifestyle factors; whether recurrent UTS further increased risk. METHODS:We conducted a prospective cohort study of 100,562 postmenopausal women aged 50-79 years without baseline hypertension. UTS were self-reported and modeled as a time-varying exposure. Effect modification by the dietary inflammatory index (DII®) and energy-adjusted DII (E- DIITM), physical activity, alcohol consumption, and neighborhood socioeconomic status were evaluated. Incident hypertension was assessed using Cox hazards models adjusted for age and metabolic, lifestyle, socioeconomic, and dietary factors. RESULTS:In unadjusted models, UTS were associated with higher incident hypertension risk (HR = 1.29; 95% CI: 1.11-1.45, p = 0.001) and after full adjustment(HR = 1.16; 95% CI: 1.02-1.35; p = 0.05). DII/E-DII did not significantly modify the association (interaction p > 0.20), while physical activity did (interaction p = 0.03). Recurrent UTS increased hypertension risk versus no stone history (HR = 1.14; 95% CI: 1.02-1.28; p = 0.03), but not versus a single episode (HR = 1.09; 95% CI: 0.96-1.23; p = 0.18). CONCLUSION:UTS were associated with a modestly increased risk of hypertension in postmenopausal women.

Abstract As smoking rates decline, obesity has emerged as the leading modifiable risk factor for cancer in the United States. With obesity rates rising, especially in younger populations, its association with increased cancer risk is becoming more evident. There is an urgent need to understand the mechanisms underlying the relationship between obesity related metabolic dysregulation and cancer risk. This session highlights transdisciplinary research from the NCI-sponsored Metabolic Dysregulation and Obesity Cancer Risk (MeDOC) Consortium, which applies integrative methods across basic science, translational models, and clinical research. The MeDOC Consortium aims to discover mechanisms linking obesity and cancer to define markers that will enhance cancer risk prediction and identify targets for intervention. Metabolic alterations include immune dysfunction, metabolite signaling, hormonal imbalance, gut microbiome and adipocyte metabolism which can disrupt several downstream signaling pathways related to cancer initiation and progression. In our novel triangulation approach, we synthesize evidence from randomized controlled trials, mechanistic animal studies, and large-scale secondary data analyses establishing population-level patterns with clinical relevance to build a comprehensive metabolic atlas of cancer risk factors. Our research topics include the gut microbiome, lipid signaling, circulating metabolites, and local and systemic immune landscape, with a focus on how these processes influence the development of colorectal, breast, and liver cancers. We will highlight complementary research projects that bridge animal studies, human cohorts, and data science across diet, inflammation, microbiome, immunity, and obesity and weight loss. We will review current evidence and describe novel applications of systems biology with big data analytics featured as tools to integrate mechanistic insights and population-level patterns to establish robust causal frameworks. Early-career investigators will participate in an open discussion on emerging challenges and opportunities in obesity and cancer research. Specifically, we will report on the role of fatty acid binding protein, ceramides, bile acids, hormones, inflammation, and gut microbiome metabolites in cancers of the colon, breast, and liver, Through a translational lens, the session will emphasize how combining data science, bench studies, and interventional trials can accelerate the discovery of biomarkers, risk stratification tools, and actionable targets for cancer prevention or interception. Citation Format: Liza Makowski, Mary Playdon, Bing Li, Sonia L. Sugg, Scott A. Summers, Cornelia M. Ulrich, Deirdre Tobias, Edward L. Giovannucci, Xuehong Zhang, James R. Hébert, E. Angela Murphy, Joeseph F. Pierre, Loretta DiPietro, Lorne J. Hofseth, Marinella Temprosa. Obesity, metabolic dysfunction, and cancer risk: Uncovering the metabolic landscape [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3628.

Background/Objectives: Unhealthy lifestyles lead to chronic low-grade inflammation, increasing the risk of colorectal cancer. Few studies in East Asia have examined the association between the dietary inflammation potential and colorectal cancer incidence. Therefore, we aimed to investigate this association further in the Japanese population. Methods: This study included 38,807 men aged 45-74 years who participated in the Japan Public Health Center-based prospective study (JPHC Study). The energy-adjusted dietary inflammatory index (E-DII) was derived from a food frequency questionnaire. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. Differences in risk due to a combination of E-DII and lifestyle were examined using interaction term. Results: During 14 years of follow-up, 1415 colorectal cancer cases occurred. A tendency to increased colorectal cancer risk was observed with consumption of pro-inflammatory diets among Japanese men (adjusted HR [95% CI] for the highest quintile: 1.20 [0.99-1.46], p trend = 0.08), with a significantly increased risk of colon cancer (HR: 1.28 [1.01-1.63], p trend = 0.03). A possible interaction was observed with alcohol consumption (p = 0.07), which was statistically significant for proximal colon cancer (HR: 1.14 [1.05-1.25] in drinkers; p interaction = 0.01). No significant interactions with other lifestyle factors were found. Conclusions: Consumption of pro-inflammatory diets increases colorectal cancer risk among Japanese men; alcohol consumption further increases this risk for drinkers. These findings suggest that colorectal cancer may be prevented through dietary modification.

BACKGROUND:Inflammatory Bowel Disease (IBD) involves genetic and environmental factors, but the relationship between disease activity, adiposity, and diet remains unclear. OBJECTIVE:To investigate the association between endoscopic/radiological activity of IBD, body adiposity, and the Dietary Inflammatory Index with or without adjustment for energy density (E-DII or DII). METHOD:An observational, cross-sectional study was carried out. Endoscopic activity was defined by an endoscopic Mayo score >2, Crohn's Disease Endoscopic Index of Severity (CDEIS) > 5, and/or the presence of a deep ulcer in any intestinal segment. Body adiposity was estimated using the body mass index, waist circumference, and waist-hip ratio (WHR). The DII and E-DII scores were calculated from a validated quantitative food frequency questionnaire. According to the DII and E-DII, the patients were divided into three groups: the first with the least pro-inflammatory diet and the third with a predominantly pro-inflammatory diet. RESULTS:Of the 62 patients, 58.1% (n = 36) were in remission (RD) and 41.9% (n = 26) had active disease (AD). The proportion of patients with overweight/obesity was 69.4% (n = 25) in the RD group and 50.0% (n = 13) in the AD group. Patients in remission exhibited significantly higher WHR (p < 0.05) and a greater frequency of central obesity (p < 0.01). A predominantly pro-inflammatory diet was common across both groups; 58.3% (n = 21) of RD patients and 50.0% (n = 13) of AD patients were in the highest DII tertile. Similar results were found for the E-DII. CONCLUSIONS:Among patients with IBD, pro-inflammatory dietary patterns and excess adiposity are highly prevalent. Despite greater central adiposity in patients in remission, no significant associations were found between DII or EDII scores and endoscopic and radiological markers of disease activity.

Introduction:The Centers for Disease Control and Prevention (CDC) funded Cancer Prevention and Control Research Network (CPCRN) is a national network which aims to accelerate the adoption and implementation of evidence-based cancer prevention and control strategies and interventions in communities, enhance large-scale efforts to reach underserved populations and reduce their cancer-related health disparities, and develop the capacity of the dissemination and implementation work force specifically in cancer prevention and control. Methods:Our site has been a part of the CPCRN since its inception in 2002 with the exception of the 2004-2009 funding cycle. As community-based participatory research is a core value of our center, we examined the development and continued engagement of our community partners using a qualitative, inductive approach to identify emergent themes from focus group sessions with current and past investigators. Results:Several key themes were identified from our analysis including long-term commitment to community partnerships and interconnectedness with other work, authentic approach, valuing our community as experts, and mutual benefits. Discussion:With our results, we provide evidence of common community-based participatory research (CBPR) principles which have supported the sustained engagement with those racial minorities who are most vulnerable in our community. While future analysis is planned to utilize this same approach with our community partners, this work marks an important step in reflecting upon the approaches which have led to our success and how they can be applied in future collaborations to maximize impact and sustained health improvements.

Supplementary Table S3 shows DQIs and pancreatic cancer risk by smoking status

Recent trends in dietary supplement use, particularly non-vitamin, non-mineral products, are not well characterized. We assessed patterns of dietary supplement use among U.S. adults from 2011 to 2023. We used data from five cycles of the National Health and Nutrition Examination Survey (NHANES 2011–2023, n = 29,216). Dietary supplement information was collected with in-home or telephone interviews by asking participants whether they used any dietary supplements in the preceding 30 days. Survey-weighted prevalence of overall and individual supplement use was calculated to be nationally representative of U.S. adults aged 20 years and older. We evaluated trends across cycles and conducted subgroup analyses by age, sex, race and ethnicity, education, body mass index, and self-reported health status. The overall use of any dietary supplements increased from 51.8

Obesity is on the verge of surpassing tobacco use as the leading modifiable cause of cancer in the U.S., contributing to over 40,000 new cancer cases annually. With obesity rates rising, especially in younger populations, its association with increased cancer risk is becoming more evident. There is an urgent need to understand the mechanisms underlying the relationship between obesity related metabolic dysregulation and cancer risk, including factors that may mitigate health disparities. Recent advances in molecular oncology and metabolic research provide opportunities in understanding the intricate connections between metabolic dysregulation, obesity, and cancer. This session will describe a novel triangulation approach, synthesizing evidence from randomized controlled trials, mechanistic animal studies, and large-scale secondary data analyses to build a comprehensive understanding of these relationships from the NCI-sponsored Metabolic Dysregulation and Obesity Cancer Risk Consortium (MeDOC). MeDOC is guided by team science and transdisciplinary approach to advance our understanding of the underlying mechanisms that connect obesity, metabolic dysregulation, and cancer risk to identify markers that will enhance cancer risk prediction and identify targets for intervention. Both obesity and metabolic dysregulation contribute to a cascade of derangements in adipocyte function, growth factors, inflammation, gut microbiome, immune function, sex hormones, lipid and glucose metabolism which, in turn, can disrupt several downstream signaling pathways related to cancer initiation and progression. These derangements occur systemically and within the tumor microenvironment itself. Through 5 individual projects and 6 collaborative projects in human and animal studies, we are currently evaluating the role of A-FABP (adipocyte fatty acid binding protein), ceramides, inflammation, gut mediated metabolites, gut microbiome dysbiosis in cancers of the colon, breast, and liver, facilitated by the coordinating center. Methodological triangulation will be emphasized throughout, demonstrating how randomized trials provide causal inference, animal studies reveal mechanistic insights, and secondary data analyses establish population-level patterns and clinical relevance. Experts from the MeDOC Consortium will review current understanding, describe the ongoing human and animal studies and big data analytic methods to establish robust causal frameworks. Open discussion will include our early career members to engage the community to identify emerging areas. Marinella Temprosa Hallmarks of metabolic dysregulation and their role in obesity cancer risk: Bing Li Harmonization of Animal Studies: Liza Makowski of Randomized and Observational Studies: James Hebert Neli Ulrich Marinella Temprosa, Bing Li, Liza Makowski, James Hebert, Cornelia Ulrich. Triangulating the metabolic crossroads: understanding the complex interplay between metabolic dysregulation and obesity cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3738.