Background: Despite the confirmed beneficial effects on preventing neural tube defects, concerns about high intakes of synthetic folate, or folic acid, in promoting cancer progression have been raised. This study evaluated the association between folate intake and prostate cancer (PCa) aggressiveness among African-American (AA) and European-American (EA) males. Methods: This study included 722 AA and 775 EA men with prostate cancer. Folate intake (dietary folate equivalent (DFE), synthetic folate, natural folate) was estimated using the National Cancer Institute Dietary History Questionnaire and detailed dietary supplement use questionnaire. Analyses included univariable comparisons of demographic and clinical characteristics of the two racial groups using the t-test or its non-parametric counterpart, the Wilcoxon test for continuous variables, and the Chi-square test for categorical variables. Logistic regression analysis was performed to evaluate the associations of each source of folate intake with PCa aggressiveness. Interaction effects between folate intake levels and racial groups were tested to evaluate if the association between folate intake and PCa differed by racial groups. Results: A greater proportion of AA subjects were diagnosed with high PCa aggressiveness compared to EAs (31.6% vs. 21.7%; p < 0.001). Both AAs and EAs had associations between decreased DFE intake and PCa aggressiveness after adjusting for covariates. Among AAs, men with the highest quartile levels of synthetic folate intake had higher odds of high-aggressive PCa compared to those with the lowest levels of intake (adj. OR = 1.39; p = 0.27), while the reversed association became stronger among EAs (adj. OR = 0.62; p = 0.14). Conclusions: The association between folate intake and prostate cancer aggressiveness appears to be source-specific and modified by race. These findings highlight the need for population-informed nutritional guidance and further investigation into nutrient-gene and dietary pattern interactions in prostate cancer progression.

Objectives: The study aimed to examine the association between a dietary index for gut microbiota (DI-GM) and the risk of incident colorectal cancer (CRC). Clarifying the role of diet-induced alterations in the composition and function of gut microbiota on the development of CRC can contribute to prevention efforts. Methods: Participants from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening trial enrolled in the intervention arm and who completed baseline assessments were included in the analysis (n = 55,685). The DI-GM is a literature-derived index used to score diet quality in terms of maintaining healthy gut microbiota. A time-dependent Cox model stratified by follow-up years (<5 and ≥5 person-years) was used to evaluate the relationships between the dietary patterns and risk of incident CRC. Results: A total of 735 incident CRC were identified over 650,470 person-years of follow-up. During < 5 years of follow-up, those with higher diet quality (DI-GM scores above 67th percentile) had an 18% lower risk of incident CRC (HRadjusted = 0.82, 95% CI: 0.63, 1.07) compared with those with lower diet quality (DI-GM scores below the 67th percentile), though effect estimates were imprecise. During ≥ 5 years of follow-up, there was no association between incident CRC and DI-GM (HRadjusted = 1.01, 95% CI: 0.80, 1.26). Conclusions: Diet quality measured using the DI-GM was associated with the risk of CRC in the first five years of follow-up in a large prospective cohort study. A diet that enhances the composition and function of gut microbiota may contribute to reduction in CRC risk.

BACKGROUND:In the Women's Health Initiative (WHI) Dietary Modification (DM) randomized trial, a low-fat dietary pattern intervention reduced breast cancer mortality (P = 0.02). Higher dietary advanced glycation end-products (dAGE) may be associated with higher breast cancer incidence. In this report, we examined whether the WHI dietary intervention influenced dAGE consumption. METHODS:Of 48,835 postmenopausal women randomized (40:60) to dietary intervention versus usual diet comparison, 40,209 had food frequency questionnaires at baseline, and serially through 5-7 years, which were used to estimate dAGE scores (kilo Unit/1000 kilocalories [kU/1000 kcal]) using a commonly referenced database. Multivariate regressions with repeated dAGE measures were examined by randomization group. RESULTS:Baseline mean dAGE scores were similar for intervention (7542 kU/1000 kcal, standard deviation (SD) = 912) and comparison (7514 kU/1000 kcal, SD = 917) groups. Through 5-7 years, dAGE scores were persistently lower in intervention versus comparison groups (mean range 5361-6236 kU/1000 kcal versus 7159-7669 kU/1000 kcal (P < 0.0001). CONCLUSIONS:The WHI low-fat dietary pattern intervention substantially reduced dAGE consumption. CLINICAL TRIAL REGISTRATION:NCT00000611; Date: 10/28/1999.

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

Diet is a potentially modifiable risk factor for breast cancer. While evidence suggests potential benefits of plant-based diets for cancer prevention, many studies lack racial and socioeconomic diversity. We examined the association of plant-based and animal-based diet indices and risk of breast cancer within the Southern Community Cohort Study (SCCS), a prospective cohort study. Data from 42,845 women among whom 1,401 were diagnosed with breast cancer during a median 12.8 years of follow-up were utilized in the analyses. We applied three previously developed plant-based diet indices—the overall plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI)—developed by Satija et al.. These indices scored individuals based on intake of 18 food groups categorized as healthful plant foods, unhealthful plant foods, or animal foods using baseline dietary data from a self-administered FFQ. Dietary intake of the 18 food groups was ranked into quintiles based on the distribution in the study population and given a positive or reverse score of 1 to 5 to later create three versions of plant-based diet indices (PDI, hPDI, and uPDI) and one animal-based index. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer risk by quartiles of dietary scores with adjustments for age, energy intake, recruitment site, race and ethnicity, education, income, insurance, smoking status, NSAIDs use, hormone therapy use, age at menopause, age at menarche, age at first birth, family history of breast cancer, physical activity, body mass index (BMI), and alcohol, and separately stratified by socioeconomic indicators. Women in the fourth quartile of the unhealthful plant-based diet score compared to the first quartile had a decreased risk of breast cancer, though confidence intervals were imprecise and included the null, HR 0.86 (95% CI:0.72, 1.02) Notably, associations appeared stronger among participants with lower socioeconomic status. Women with income ≤ $25,000 had stronger associations than those with higher income for the unhealthful plant-based diet score; HRs (95% CIs) were 0.80 (0.65, 0.97) and 1.07 (0.76, 1.52), respectively. Among those with lower education (≤ high school graduation), the HR for high unhealthful plant-based diet index was 0.77 (95% CI: 0.61, 0.97), while the HR was 0.95 (95% CI: 0.72, 1.27) for individuals with vocational, technical, business training, college, or college graduation, and 1.24 (95% CI: 0.63, 3.46) for those with graduate-level education. No substantial associations with breast cancer were observed for the PDI, hPDI, or animal-based indices. We observed that higher scores on an unhealthful plant-based diet index were associated with a reduced risk of breast cancer, primarily among individuals with lower income or education. These associations were unexpected and need to be confirmed in other large prospective cohort studies in diverse populations. Jessica Sainyo, Susan E. Steck, Monique J. Brown, Jiajia Zhang, Brie Turner-McGrievy. Association between plant-based and animal-based diet indices and breast cancer risk in the Southern Community Cohort Study (SCCS) [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr A061.

Higher intake of ultra-processed foods is associated with increased risk of obesity and type 2 diabetes, but evidence is limited on associations of metabolomics and proteomics with ultra-processed foods and liver diseases. We aimed to evaluate associations of metabolomic and proteomic signatures related to ultra-processed food intake with liver cancer and liver disease. Data from a total of 173, 840 participants aged 40-69 years from the UK Biobank were analyzed. Ultra-processed food intake was assessed by 24-hour dietary recalls. Metabolites were measured by nuclear magnetic resonance spectroscopy and plasma proteome was profiled using the Olink platform. Liver disease outcomes were ascertained using data from the in-hospital, cancer registry, and death registry including metabolic dysfunction-associated steatotic liver disease (MASLD), cirrhosis, liver cancer, and severe liver disease (hepatocellular carcinoma and other severe liver diseases). Elastic net regression with 10-fold cross validation was used to calculate the omics signatures related to ultra-processed food intake. We used Cox proportional hazards regression models to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for ultra-processed food intake and its omics signatures and liver disease outcomes adjusting for multiple potential confounding factors. With a median of 8.9 years follow-up, ultra-processed food intake was positively associated with risk of MASLD (HR Tertile 3 vs. tertile 1 1.42; 95% CI 1.21-1.67), cirrhosis (HR 1.25; 95% CI 1.05-1.48), and severe liver disease (HR 1.52; 95% CI 1.21-1.91) but not with liver cancer (HR 1.30; 95% CI 0.89-1.91). The metabolic signature score of ultra-processed foods was positively associated with risk of MASLD (HR 3.25; 95% CI 2.06-5.14). The proteomic signature score of ultra-processed foods was positively associated with risk of MASLD (HR 1.99; 95% CI 1.04-3.80) and cirrhosis (HR 2.00; 95% CI 1.12-3.60). A total of 34 metabolites and 65 proteins were significantly associated with ultra-processed food intake based on the multivariable-adjusted model and elastic net regression. These metabolites and proteins are linked to biological pathways such as lipids metabolism, oxidative stress, and inflammatory response. Ultra-processed food intake and its metabolic and proteomic signatures are positively associated with risk of adverse liver outcomes. Longgang Zhao, 1 Yun Chen, 1 Alyssa Clay-Gilmour, 2 Jiajia Zhang, 2 Xuehong Zhang, 1 Susan Steck2. Metabolomic and proteomic signatures of ultra-processed foods with liver cancer and liver disease [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 977.

Prostate cancer (PCa) disparities present as a complex public health challenge rooted in a multifaceted interplay between biological, social, and environmental factors, herein termed biosocial synergy. Reactive metabolites known as Advanced Glycation End Products (AGEs) play a unique role at the nexus of biosocial synergy. Communities experiencing the highest cancer burden are more likely to be exposed to health inequity risk factors that increase AGE accumulation in the body, which has been linked to various chronic diseases. Previous research from our group demonstrated that nutritional inequity resulting from biosocial synergy enhances AGE bioavailability, influencing the tumor microenvironment and promoting PCa progression. Building on our published work, we are generating population specific patient-derived primary cell lines to investigate the mechanistic effects of AGE signaling on tumor biology, aiming to develop an innovative health inequity framework to address cancer disparity outcomes. Patients were consented according to our IRB protocol #20210623. Prostatectomy tissues were graded by our licensed pathologist and enzymatically processed into patient-matched epithelial and fibroblast population specific lines, which underwent molecular characterization. 2D and 3D co-culture models with these patient-matched lines were used to study the effects of AGEs on prostate tumor growth and the roles of AGE and receptor for AGE (RAGE) within the tumor microenvironment. To connect mechanism and epidemiology, we evaluated the correlation between AGE consumption and PCa outcomes using a diet questionnaire processed through an AGE algorithm. AGE introduction in the extracellular matrix replicated the activated response observed in prostate tumor tissues, evident in the differential ability of population specific fibroblasts to enhance epithelial cell migration via cancer-associated fibroblast (CAFs) activation. Direct AGE treatment also increased the invasive capacity of tumor epithelial cells cultured in 3D microfluidic co-cultures. This fostered a population specific pro-tumorigenic microenvironment conducive to tumor migration. In addition, epidemiological studies in a large patient cohort showed increased odds of aggressive PCa among Black men who consumed high levels of AGEs. There is a critical need for experimental models that can effectively reflect the highly dynamic nature of biosocial synergism on cancer outcomes. Increased AGE bioavailability offers an untapped opportunity to explore how biosocial synergy can impact tumor biology across population groups to promote aggressive disease. Reporting on transdisciplinary studies of AGE research could illuminate optimal strategies for overcoming health inequity barriers in cancer prevention, treatment, and survivorship for high-risk populations. Tuong Vi V. Nguyen, Boxiao Ding, Bradley A. Krisanits, Susan E. Steck, Steven C. Smith, Lance J. Hampton, Paula D. Bos, Nolan W. Wages, Victoria J. Findlay, David P. Turner. Advanced glycation end products provide insight into tumor associated biosocial synergy to inform on prostate cancer disparities [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr A059.

While mentorship is traditionally perceived as top-down where seasoned academics guide earlier career individuals, we assert that mentorship is inherently bi-directional, with multi-perspective exchanges shaping our daily work. Community-engaged research challenges the traditional model by fostering reciprocal mentorship between researchers, students and community members, and this all hinges on trust. Community champions bring invaluable lived experiences, contextual knowledge, and cultural insights to research approaches, assessments, and interventions, making them essential mentors in health behavior research. This paper shares perspectives from a survey of researchers on partnership development and community-engagement. Findings showed the value of community partners as mentors and the role of trust for long-lasting relationships. Over half of faculty engaged communities in research resulting in actionable results addressing quality of life issues. Community-engaged collaborations were beneficial for improving partnership- and grant-related outcomes. We provide recommendations for building trust, setting expectations, and defining roles in community-academic mentorship relationships.

BACKGROUND:Higher consumption of ultra-processed foods is associated with increased risk of obesity and type 2 diabetes; however, evidence on liver diseases and the underlying mechanisms remain limited. OBJECTIVES:This study aimed to evaluate associations between metabolomic and proteomic signatures of ultra-processed food intake and adverse liver outcomes. METHODS:Data of participants aged 40 to 69 y from the UK Biobank (N = 173,840) were analyzed. Ultra-processed food intake was assessed using multiple 24-h dietary recalls. Plasma metabolites were measured using nuclear magnetic resonance spectroscopy, and plasma proteome was profiled using the Olink platform. Adverse liver outcomes (metabolic dysfunction-associated steatotic liver disease [MASLD], cirrhosis, liver cancer, and severe liver disease) were ascertained using data from the in-hospital records or cancer or death registries. We used elastic net regression to calculate omics signatures of ultra-processed foods and Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for ultra-processed foods and their omics signatures and adverse liver outcomes, adjusting for multiple potential confounding factors. RESULTS:With a median follow-up of 8.9 years, an increase of 1 standard deviation (SD) in metabolic signature score of ultra-processed foods was associated with increased risk of MASLD (HR: 1.61; 95% CI: 1.38, 1.87). An increase of 1 SD in proteomic signature score of ultra-processed foods was associated with increased risk of MASLD (HR: 1.84; 95% CI: 1.45, 2.35), cirrhosis (HR: 1.49; 95% CI: 1.16, 1.91), and severe liver disease (HR: 1.48; 95% CI: 1.07, 2.03). Thirty-four metabolites and 65 proteins were significantly associated with ultra-processed food intake and were enriched in biological pathways such as lipid metabolism, immune, and inflammatory response. About half of these metabolites and proteins are significantly associated with risk of MASLD and cirrhosis. CONCLUSIONS:Ultra-processed food intake and its metabolic and proteomic signatures are positively associated with risk of MASLD.

The Social Vulnerability Index (SVI) assesses the overall vulnerability to external stressors of a geographic area by scoring 16 United States Census variables related to four overall categories: housing type and transportation, household characteristics, racial and ethnic minority status, and socioeconomic status. Previous research suggests that areas with lower socioeconomic status have higher incidence rates of breast cancer, but the relationship between the SVI and breast cancer incidence has been less well studied. Data from the North American Association of Central Cancer Registries (NAACCR), containing county-level incidence rate data for all breast cancer cases reported to cancer registries, was used to create a choropleth map in ArcGIS Pro. The SVI for each county in the United States provided by the Centers for Disease Control and Prevention (CDC) was used to create a choropleth map to identify areas of highest vulnerability. The breast cancer and SVI maps were combined into a bivariate choropleth map to identify counties with overlapping high breast cancer incidence and high social vulnerability. A bivariate spatial association was performed using Lee’s L statistic to identify areas of statistically significant high and low SVI and high and low breast cancer incidence. Perimeter regions around the United States have the highest SVI, with a few other high SVI counties scattered throughout the country. Breast cancer incidence rates were elevated in the midwestern and eastern portions of the United States, with the highest incidence rates per capita in a few counties in the northwest. When analyzing the bivariate spatial association, Lee’s L was statistically significant. The bivariate maps identified areas of high SVI and high breast cancer incidence rates scattered throughout the country, with many of the southeastern counties falling into this category. Areas of low social vulnerability and high breast cancer incidence rates were primarily concentrated in the midwestern states. The southwestern portion of the United States had a statistically significant spatial association with high SVI and low breast cancer incidence rates. Areas with high social vulnerability and high incidence rates of breast cancer are primarily observed in the southeastern region of the United States. Further research would be beneficial to understand the specific underlying risk factors contributing to the statistically significant spatial associations in the southwest region. Identifying geographic areas of high SVI and high breast cancer incidence can assist in targeting screening and prevention programs to areas of need. Anna Marie Pavy, Cassie Odahowski, Monique J. Brown, Stella Self, Lauren E. McCullough, Susan E. Steck. Social vulnerability and breast cancer incidence in the United States: A county-level bivariate analysis [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr A015.

Background: Higher diet quality has been associated with reduced hypertension risk in the general population. Although women cancer survivors are at elevated risk of hypertension following cancer treatment, it is unclear if diet quality is also associated with risk of hypertension among women cancer survivors. Methods: We analyzed 1,441 women (aged 35 to 74 years) from the Sister Study (2003-2009) who reported a history of cancer other than non-melanoma skin cancer and had no prevalent hypertension at enrollment. Prevalent hypertension was defined as systolic blood pressure (BP) ≥140 mmHg, diastolic BP ≥90 mmHg, or the use of antihypertensive medication at enrollment. Participants diagnosed with cancer within one year of enrollment were excluded. The median time since diagnosis was 11.4 years. Participants were followed through September 2021 (median follow-up: 11.6 years). Dietary quality was assessed using the validated 110-item Block food frequency questionnaire and categorized into quartiles based on the entire Sister Study population for Dietary Approaches to Stop Hypertension (DASH), Healthy Eating Index (HEI-2015), alternate Mediterranean diet (aMED), and alternative Healthy Eating Index (aHEI-2010). Incident hypertension was self-reported as a new diagnosis or initiation of antihypertensive medication at any time during follow-up. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident hypertension. Results: After adjusting for potential confounders, higher DASH scores were associated with decreased risk of incident hypertension (HR Q4vsQ1 0.63, 95% CI 0.48-0.84, P trend =0.01). Associations were weaker for aMED (HR Q4vsQ1 0.78, 95% CI 0.59-1.03, P trend =0.09) and HEI-2015 (HR Q4vsQ1 0.78, 95% CI 0.60-1.03, P trend =0.12), and no significant association was found for aHEI-2010. A 5-year lag analysis yielded similar results. DASH remained associated with reduced hypertension risk even after adjusting for pre-existing diabetes, dyslipidemia, and cardiovascular disease history. The association between DASH and hypertension risk was not evident in long-term survivors (≥15 years post-diagnosis). A stricter hypertension definition (BP ≥130/80 mmHg) did not materially change the findings. Conclusion: Our findings suggest that higher diet quality, particularly following DASH dietary patterns is associated with reduced risk of hypertension in women cancer survivors.

Abstract INTRODUCTION: Physical activity may improve quality of life and reduce mortality among cancer survivors. As cancer death rates continue to decrease, the population of cancer survivors is expected to grow, therefore making it important to study their health behaviors. Research has been conducted on prevalence of physical activity and sedentary behaviors of survivors of certain cancers, however, little research has been conducted comparing cancer survivors to individuals without cancer. The purpose of this study was to update previously published results from earlier National Health and Nutrition Examination Survey (NHANES) cycles (2007-2010) with more recent data comparing physical activity and sedentary behavior among cancer survivors and individuals without cancer. METHODS: Using the NHANES 2011-2018, we identified 1320 cancer survivors and 19,109 participants without cancer who provided data on recreational, work-related, and transportation-related physical activity and sedentary behavior. The included participants were over 20 years of age, not pregnant at the time of the survey, and were more than three years from their cancer diagnosis, if applicable. Comparisons between cancer survivors and individuals without cancer were conducted for duration of total physical activity (min/day) and sedentary time per day. To account for the complex sampling design, weighted multivariable analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Compared to individuals without cancer, cancer survivors reported less average ± standard error physical activity minutes per day (190.06 ± 5.24 and 147.29 ± 13.14, respectively), and slightly more sedentary hours per day (6.95 ± 0.09 and 7.56 ± 0.36, respectively). However, after adjusting for age, race and ethnicity, sex, educational status, body mass index, and smoking status, there was no association between physical activity duration or sedentary time and cancer survivor status. The OR (95%CI) for more than 60 minutes per day of physical activity was 1.00 (0.83, 1.20) compared to no physical activity, and for more than 8 hours of sedentary time per day was 1.00 (0.82, 1.21) compared to less than 5 hours per day. DISCUSSION: In a previous publication of earlier cycles of NHANES (2007-2010), cancer survivors reported higher physical activity but also higher sedentary time per day compared to individuals without cancer. However, these results were not supported in this updated analysis using more recent NHANES cycles (2011-2018). After adjustment for important covariates, we did not find differences between cancer survivors and individuals without cancer in reported physical activity or sedentary time. Further research in other populations is needed to corroborate these findings and document whether they reflect a growing awareness of the negative impact of sedentary behavior in cancer survivorship. Citation Format: Anna Marie Pavy, Susan E. Steck. Physical activity and sedentary behavior of cancer survivors compared to individuals without cancer in NHANES [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3413.

The aim of the study was to develop and evaluate a novel dietary index for gut microbiota (DI-GM) that captures dietary composition related to gut microbiota profiles. We conducted a literature review of longitudinal studies on the association of diet with gut microbiota in adult populations and extracted those dietary components with evidence of beneficial or unfavorable effects. Dietary recall data from the National Health and Nutrition Examination Survey (NHANES, 2005–2010, n = 3812) were used to compute the DI-GM, and associations with biomarkers of gut microbiota diversity (urinary enterodiol and enterolactone) were examined using linear regression. From a review of 106 articles, 14 foods or nutrients were identified as components of the DI-GM, including fermented dairy, chickpeas, soybean, whole grains, fiber, cranberries, avocados, broccoli, coffee, and green tea as beneficial components, and red meat, processed meat, refined grains, and high-fat diet (≥40% of energy from fat) as unfavorable components. Each component was scored 0 or 1 based on sex-specific median intakes, and scores were summed to develop the overall DI-GM score. In the NHANES, DI-GM scores ranged from 0–13 with a mean of 4.8 (SE = 0.04). Positive associations between DI-GM and urinary enterodiol and enterolactone were observed. The association of the novel DI-GM with markers of gut microbiota diversity demonstrates the potential utility of this index for gut health-related studies.

Background Calcium and magnesium are important micronutrients necessary for normal body functioning. Objective The objective of the study was to approximate usual nutrient intakes and estimate proportion of adults meeting the Estimated Average Requirement (EAR) of calcium and magnesium from diet, and diet plus supplements (total intake). Trends the proportion of adults meeting the EAR were estimated by sex, age, and race and ethnicity. Design The study utilized data from the National Health and Nutrition Examination Survey, a cross-sectional survey of a nationally representative sample of the US civilian and noninstitutionalized population. Participants and setting The continuous National Health and Nutrition Examination Survey survey data from 2003-2004 through 2017-2018 for dietary intake, and 20072008 through 2017-2018 for total intake were analyzed. The study sample included men and women (not lactating/pregnant) ages 19 years and older with 2 reliable 24-hour dietary recalls and energy intake >500 to <6,000 kcal/day (N = 35 037). Main outcome measures Mean daily intake and trends of proportion of adults meeting/exceeding the EAR for calcium and magnesium were estimated. Statistical analyses performed The National Cancer Institute's method was used to calculate daily intakes for calcium and magnesium by demographic subgroups. SAS SURVEYMEAN and SURVEYFREQ procedures were used to estimate means f SE for continuous variables and frequencies and percentages for categorical variables, and 2 sample t test for P values. Trends were estimated with National Cancer Institute's Joinpoint trend analysis program. Results Mean daily dietary calcium intake and proportions of adults meeting the EAR from both diet and supplements was lowest among women (859 mg [61.9%]), adults ages 71 years and older (865 mg [60.3%]) and non-Hispanic Black individuals (782 mg [48.6%]) compared with men, younger age groups, and other races and ethnicities. Magnesium intake reported from diet was lowest in adults ages 71 years and older (276 mg), whereas total magnesium intake and proportion of meeting the EAR from both diet and supplements was lowest in women (302 mg) and men (52%), respectively, adults ages 19 to 30 years (305 mg [48.5%]), and non-Hispanic Black individuals (274 mg [35.5%]). The trends in the proportion of women and non-Hispanic White adults meeting the EAR from total calcium intake decreased significantly (P P <.05) by 2.9% and 2.0%, respectively. Conclusions Women and adults ages 71 years and older had the lowest reported mean daily dietary calcium intake and proportion meeting the EAR for calcium from diet and supplements. Men and adults ages 19 to 30 years had the lowest proportion meeting the EAR for magnesium from diet and supplements with adults ages 19 to 30 years also having the lowest reported total magnesium intake from diet and supplements. Non Hispanic Black individuals had the lowest proportion of meeting the EARs for calcium and magnesium from reported total intake. The trends in the proportion of women and non-Hispanic White individuals meeting the EARs for calcium through total intake decreased over time and remained stable in other subpopulations and for magnesium.

Introduction: A previous genome-wide association study (GWAS) investigated joint and independent genetic factors in recipients and donors contributing to death in the first year after unrelated donor HCT (DISCOVeRY-BMT study, PMID: 34746714). The current study leveraged DISCOVeRY-BMT data to identify non-human leukocyte antigen (HLA) genetic factors related to poor and exceptional survivorship after allogeneic HCT. Methods: DISCOVeRY-BMT, a collaboration with the Center for International Blood and Marrow Transplant Research (CIBMTR) consists of 2 cohorts of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS) patients treated 2000-2011 and their ≥8/8 HLA-matched unrelated donors. Standard genotyping using the Illumina OmniExpress BeadChip and quality control were performed. Imputation used the Trans-Omics in Precision Medicine (TOPMed) Imputation Server (GRCh38). Given 80% of patients who survive 24 months post-HCT survive to 10 years (PMID: 28232372), we categorized patients who were alive with <120 but >24 months follow-up as exceptional survivors. Standard and poor survivors are those who died between 24-120 months post-HCT and <24 months post-HCT, respectively. GWAS was performed with additive multivariable logistic-Firth hybrid regression models adjusting for age at HCT, sex, cohort, disease (AML, ALL, MDS), disease status (early or advanced), year of HCT, and principal components. Summary statistics and median survival in months were calculated in R.4.4.1. P < 5 × 10⁻⁸ denoted genome-wide significance. Results: Study sample consisted of 2886 European ancestry recipients, with survivors comprising 32% exceptional (N=937, median survival=142 months), 15% standard (N=441, median survival=47 months), and 53% poor (N=1508, median survival=5 months). Distributions by disease (17-21% ALL, 60-62% AML, 18-21% MDS) were similar in exceptional, standard, and poor survivor cases. Exceptional survivor cases had slightly higher early and lower advanced disease status (82% early, 18% advanced) compared to standard (71% early, 29% advanced) and poor survivors (64% early, 36% advanced). Single nucleotide polymorphism (SNP) rs7375273 on chromosome 4 (RXFP1) showed marginal genome-wide significance (OR=1.49, 95% CI=1.29-1.72, P=8.93E-08), that allele A is associated with increased odds of poor survivorship compared to all others (exceptional+standard). Although marginally genome-wide significant, the A allele of rs7507979 on chromosome 19 (INSR) showed increased odds of exceptional survivorship compared to poor survivors (OR=1.40, 95% CI=1.23-1.59, P=2.49E-07). Conclusions: Using GWAS approach, we identified marginally significant variants in recipients associated with poor and exceptional survivorship. Rs7375273 is located within the RXFP1 (relaxin family peptide receptor 1) gene and is implicated in pathways involving G protein-coupled receptor activity and hormone binding. Previous GWAS have associated SNPs in RXFP1 with ALL (ETV6-RUNX1 positive). RXFP1 is differentially expressed in non-small cell lung cancer and is associated with poor survival. OpenTarget and eQTLgen provide in silico evidence linking rs7375273 to eQTLs within FNIP2 and changes in gene expression of whole blood. FNIP2 may impact leukemia survival post-HCT by regulating the mTOR pathway, immune responses, cellular stress mechanisms, and leukemia cell biology. INSR (insulin receptor), through ligand binding, activates its receptor INSR, initiating the insulin signaling pathway which governs glucose uptake, release, and the synthesis/storage of carbohydrates, lipids, and proteins. INSR has been implicated in GWAS traits such as triglyceride levels, blood pressure, body height, and cardiovascular disease. INSR plays a crucial role in cancer, particularly in the tumor vasculature of colorectal carcinoma, renal cell cancer, and gastric adenocarcinoma, where its elevated expression levels are associated with shorter survival. Further research is necessary to elucidate these mechanisms. Our future directions include expansion into larger, more diverse populations and replication in independent cohorts. This work strives to further delineate genomic predictors for HCT outcomes to better understand recipient inherited predisposition and identify novel mechanisms of survivorship post-HCT.

Abstract Objective: Results of studies examining the association between a plant-based diet or animal food intake and prostate cancer have been mixed. Few studies have focused on aggressive prostate cancer in a racially diverse population. We examined the association between healthy and unhealthy plant-based and animal-based diet scores and aggressive prostate cancer in the North Carolina-Louisiana Prostate Cancer Project, a case-only study of Black and White men in the United States. Methods: Eighteen food groups were created and classified as healthy plant foods, unhealthy plant foods, or animal foods using dietary data collected from an interviewer-administered modified version of the National Cancer Institute Diet History Questionnaire among 909 Black and 991 White men with a histologically confirmed diagnosis of prostate cancer. High aggressive prostate cancer (n=332) was defined as Gleason sum ≥8; or PSA> 20ng/ml; or Gleason sum ≥7 and clinical stage T3-T4, and the comparison group was all other prostate cancer cases (n=1,568). Logistic regression was used to determine the odds ratio (OR) and 95% confidence intervals (95% CI) for high aggressive prostate cancer by tertiles of dietary pattern scores. Results: A decreased odds of aggressive prostate cancer was observed among men in the upper compared to the bottom tertile for healthy plant-based diet score (OR: 0.82, 95% CI: 0.58, 1.15) and unhealthy plant-based diet score (OR: 0.89, 95%CI: 0.63, 1.25) while an increased odds was observed comparing extreme tertiles of the animal-based diet score (OR: 1.17. 95% CI: 0.84-1.65) after adjustment for multiple covariates, though confidence intervals were imprecise and not statistically significant. Associations tended to be stronger among White men than among Black men; e.g., for the animal-based diet score, ORs (95% CIs) were 1.41 (0.86, 2.37) and 1.02 (0.63, 1.66) for White and Black men, respectively. Conclusions: Consuming a plant-based dietary pattern may be associated with lower odds of aggressive prostate cancer while an animal-based dietary pattern may be associated with higher odds, though associations were weak and not statistically significant. Keywords: Healthy plant-based diet, unhealthy plant-based diet, animal-based diet, aggressive prostate cancer, racial disparities Conflict of interest: None Funding: PCaP is carried out as a collaborative study supported by the Department of Defense contract DAMD 17-03-2-0052. This research was made possible in part by Grant Numbers R01-CA259415 from NIH-NCI and T32-GM081740 from NIH-NIGMS. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIGMS or NIH. Citation Format: Jessica Sainyo, Susan E. Steck, Longgang Zhao, L. Joseph Su, Lenore Arab, David Turner, Ebonee N. Butler, Jeannette T. Bensen, Elizabeth T.H. Fontham, James L. Mohler. Associations between plant- and animal-based dietary patterns and aggressive prostate cancer in the North Carolina-Louisiana prostate cancer project (PCaP) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2172.

Background: Ultra-processed food (UPF) intake has been positively associated with obesity and diabetes. The relationship between UPF intake and liver health has been scarcely studied. Objectives: We aimed to evaluate the association of UPF intake with risk of adverse liver outcomes including nonalcoholic fatty liver disease (NAFLD), liver fibrosis/cirrhosis, liver cancer, severe liver disease, and serum biomarkers of liver health. Methods: A total of 173,889 participants aged 40 to 69 y from the UK Biobank were included. UPF intake was defined using 24-h dietary recalls and NOVA classification. Liver outcome data were obtained from cancer registry, in-hospital records, and death registries. Serum biomarkers were measured at baseline. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between UPF and adverse liver outcomes adjusting for demographics, lifestyle factors, body mass index, and diabetes. We used multinomial logistic regression to evaluate associations between UPF and liver function biomarkers. Results: After a median follow-up of 8.9 y, we documented 1108 NAFLD, 350 liver fibrosis/cirrhosis, 134 liver cancer, and 550 severe liver disease cases. Higher UPF intake was associated with increased risk of NAFLD (HRQuartile 4 vs. Quartile 1: 1.43; 95% CI: 1.21, 1.70; P-trend < 0.001), liver fibrosis/cirrhosis (HR: 1.18; 95% CI: 0.87, 1.59; P-trend = 0.009), and severe liver disease (HR: 1.50; 95% CI: 1.19, 1.90; P-trend < 0.001) but not with liver cancer (HR: 1.00; 95% CI: 0.63, 1.58; P-trend = 0.88). Higher UPF intake was associated with elevated levels of C-reactive protein, alkaline phosphatase, aspartate aminotransferase, gamma-glutamyltransferase, and triglycerides and lower cholesterols (all P-trend < 0.001). Conclusions: Higher UPF intake is associated with an increased risk of NAFLD, liver fibrosis and cirrhosis, and severe liver disease and adverse levels of multiple clinical biomarkers, suggesting the potential importance of reducing UPF intake to improve liver health.

It is unclear whether diet-associated inflammation is related to the development of anxiety disorders. We aimed to investigate the association between energy-adjusted dietary inflammatory index (E-DII) scores and the incidence of anxiety disorders, and explore the joint effects of E-DII scores with other inflammatory lifestyles in enhancing anxiety risk. In the UK Biobank Study of 96,679 participants, baseline E-DII scores were calculated from the average intake of at least two 24 h dietary recalls. Multivariable-adjusted Cox models were used to evaluate the associations between E-DII scores and the incidence of total anxiety disorders, and primary types and subtypes; additive and multiplicative interactions of a pro-inflammatory diet and seven inflammatory lifestyles were examined. After a median follow-up of 9.4 years, 2785 incident cases of anxiety disorders occurred. Consuming a pro-inflammatory diet was significantly associated with a higher risk of total anxiety disorders (HRQ4vsQ1 = 1.12, 95% CI = 1.00–1.25), and positive associations were consistently identified for primary types and subtypes of anxiety disorders, with HRs ranging from 1.08 to 1.52, and were present in women only. Both additive and multiplicative interactions of current smoking and a proinflammatory diet on total anxiety risk were identified. A proinflammatory diet was associated with a higher incidence of anxiety disorders, and current smoking may synergize with a proinflammatory diet to promote anxiety risk, particularly among women.

Abstract In the US, over 18 million people are living with a cancer diagnosis and that number may double by 2050. There is a need to unite research across the cancer continuum to address the needs of cancer survivors to ensure optimal quality of life and improve mortality outcomes. Health constructs that influence cancer survivorship are multifactorial, highly dynamic, and vary across the lifespan. This makes assigning their impact on the well-being and future outcomes of cancer survivors challenging. As a pathophysiological process that lies at the intersection between societal, environmental, and biological constructs, it is proposed that the irreversible accumulation of metabolites called advanced glycation end products (AGEs) can inform on quality of life and mortality outcomes for cancer survivors. It is proposed that AGE accumulation as a result of societal, environmental, and biological constructs overwhelm the fragile equilibrium that maintains AGE homoeostasis to impact tumor biology and cancer outcomes. The relationships between health constructs and AGE exposure are epitomized by nutritional behavior. The consumption of cheaper unhealthier often ultra-processed foods are inherently AGE laden and the excessive consumption of foods high in fats and sugars that promote obesity and increase cancer risk readily provide reactive intermediates that fuel AGE formation in cells and tissues. Our collaborative epidemiological studies assign high levels of AGE consumption with increased breast cancer risk, aggressiveness, and mortality, which is supported by translational studies showing that circulating AGE levels in breast cancer patients correlate with worse disease-free survival and other poor prognosis indicators. Critically, this group has also shown that chronic AGE consumption by mice increases prostate tumor growth (p<0.001), and causes a rapid progression through prostate intra-epithelial neoplasia (p=0.049), adenocarcinoma (p=0.042) and metastasis (p=0.001). Consumption of the high AGE diet caused a regulatory program of stromal activation conducive for tumor growth. As a bio-social determinant of health AGE accumulation and its pathogenic effects serve as informative and/or functional markers indicative of the current health status and well-being of cancer survivors and may inform of potential future outcomes. Our studies show that physical activity and dietary intervention (cardiac rehabilitation) reduced systemic AGE levels in breast cancer survivors. Therefore, prevention and control interventions aimed at reducing AGE exposure represent viable strategies for improving quality of life and disease recurrence for cancer survivors. This research was made possible in part by Grant Numbers R01-CA259415, R01-CA245143, R21-CA194469, and U54-CA210962 from NIH-NCI. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NIH. Citation Format: David P. Turner, Bradley A. Krisanits, Marvella E. Ford, Lindsay L. Peterson, Susan E. Steck, Paula D. Bos, Victoria J. Findlay. AGEing and lifestyle after a cancer diagnosis: A balanced equilibrium for survivorship [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3409.