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.

Eswatini (formerly Swaziland) has one of the highest prevalence rates of HIV at 25.4% and only recently implemented an HPV vaccine in 2023. The country also reported the highest incidence and mortality rates of cervical cancer in 2021, estimated at 84.5 and 55.7 per 100,000 female population, respectively. This study serves as the first survival analysis of cervical cancer patients in Eswatini, aimed at examining the impact of clinical and demographic factors on cervical cancer survival outcomes. The Eswatini Cancer Registry was screened for cancer patients from 2016 to 2024, yielding a total of 2,349 cervical cancer patients, of whom 603 deaths were analyzed using the Cox proportional hazards model. The primary analysis assessed the association between cancer stage at diagnosis and survival, adjusting for potential confounders (age, smoking status, HIV status, treatment, and basis of diagnosis). Most patients (44.27%) were aged 50 years or older at diagnosis, whereas 31.42% were between 40 and 49 years and 24.31% were 39 years or younger. A significantly higher proportion of patients did not receive any treatment (59.05%, p < 0.001). Advanced cancer stages (Stages 3 and 4) were associated with significantly reduced survival times, with Stage 4 patients experiencing a median survival of about 10 months compared to about 40 months for Stage 1. Treatments (chemotherapy, radiation, surgery) reduced the hazard of death by 30% (HR: 0.70, 95% CI: 0.59-0.84, p < 0.001). In this first population-based survival analysis of cervical cancer in Eswatini, advanced stage at diagnosis and lack of treatment emerged as the strongest predictors of mortality, consistent with evidence in survival of cancer patients. These findings highlight the urgent need to expand access to screening, ensure early detection, and strengthen treatment capacity.

Breast cancer remains the most commonly diagnosed cancer and a leading cause of cancer-related mortality among women in the United States. While many risk factors have been identified, a substantial proportion of breast cancer cases occur in individuals without known risk profiles, underscoring the need to investigate novel genetic and epigenetic contributors. DNA methylation, an epigenetic modification regulated by DNA methyltransferase (DNMT) enzymes, plays a critical role in gene expression and genomic stability. This nested case‒control study, conducted within the Arkansas Rural Community Health study (ARCH) cohort, examined the associations between polymorphisms in DNMT1, DNMT3A, and DNMT3B and breast cancer risk. Using TaqMan genotyping and genome-wide association analysis in a sample of 2,407 participants (967 cases and 1,440 controls), we assessed both individual single-nucleotide polymorphisms (SNPs) and haplotypes. DNMT3A SNP rs7605753 was significantly associated with increased breast cancer risk according to a recessive model (adjusted odds ratio [aOR]: 1.30; 95

Abstract Background: Prostate cancer (PCa) is the second most common type of cancer among men worldwide. Environmental exposure to arsenic has been implicated in PCa carcinogenesis and progression through various pathways. This study assessed arsenic species and methylation indices and their association with aggressive PCa. Methods: We analyzed data from 1,497 men (722 Black and 775 White) enrolled in the North Carolina-Louisiana Prostate Cancer Project (PCaP), including 396 with high and 1,101 with low aggressive PCa. Urinary arsenic species concentrations were quantified using HPLC-ICPMS and adjusted for urine dilution using creatinine. We assessed the arsenic species including inorganic arsenic (iAs), monomethylarsonate (MMA), and dimethylarsinate (DMA) and methylation indices (Primary Methylation Index and Secondary Methylation Index) between low vs. high aggressive groups using univariable tests. We also performed multivariable logistic regression models, adjusting for screening history, waist-to-hip ratio (WHR), age, smoking status, study site and race. Results: Univariable comparisons showed no significant difference in individual arsenic species and methylation indices with low vs. high aggressive PCa (all p>0.10). However, median concentrations of total inorganic arsenic (iAs+DMA+MMA) showed a marginal difference between low vs. high aggressive PCa (1.34[0.39-2.68] vs. 1.49[0.62-3.02], p=0.06). When comparing race, Black and White men had similar levels of total iAs (1.35[0.42-2.86] vs. 1.39[0.46-2.68]; p=0.83). Multivariable logistic regression models showed overall positive association with elevated arsenic concentrations, with tertile 2 and 3 showing significantly higher odds of aggressive PCa (OR: 1.39, 95% CI: 1.01-1.91, p = 0.04 and OR: 1.45, 95%CI: 1.07-1.97, p = 0.02, respectively). A significant linear trend was also observed across increasing total iAs tertiles (p-trend=0.02). Race-stratified models showed significant association for White men (OR: 1.68, 95% CI: 1.05-2.67, p = 0.03) and not statistically significant association for Black men (OR: 1.34, 95% CI: 0.89-2.03, p = 0.16). Race did not modify the association between total iAs and aggressive PCa (p-interaction = 0.76). PMI and SMI were not significantly associated with aggressive PCa in adjusted models (OR: 1.01, 95% CI: 0.81-1.25, p = 0.91; and OR: 1.13, 95% CI: 0.96-1.33, p = 0.14). Conclusions: Our findings show that elevated urinary inorganic arsenic levels are associated with increased odds of aggressive prostate cancer, independent of race and methylation efficiency. The results point to inorganic arsenic, rather than its methylated metabolites, as the key chemical driver of prostate cancer progression. This connection between arsenic speciation and prostate cancer aggressiveness underscores the translational importance of environmental chemistry in cancer prevention. Citation Format: Sithembiso S. Msibi, MinJae Lee, Ping-Ching Hsu, L. Joseph Su. Urinary arsenic speciation and metabolic indices associate with exposure chemistry and prostate cancer aggressiveness [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 7649.

Abstract BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC) is rising, yet a robust model of underlying factors across diverse populations is unknown. Most studies have examined a single factor or were performed in non-diverse population. The collection of comprehensive, patient-reported data across different populations in CRC will enable a deeper understanding of these associations to inform early intervention strategies. METHODS: A pilot survey study was conducted at UT Southwestern Simmons Comprehensive Cancer Center (SCCC) and its affiliated safety-net hospital, Parkland Health and Hospital System (PHHS). The objective was to evaluate the feasibility of a multidomain survey in colorectal cancer patients. Eligible patients (≥18 years, stage I-IV adenocarcinoma, diagnosed within 12 months) completed baseline surveys in English or Spanish on demographics, lifestyle, symptom burden, nutrition (Dietary History Questionnaire), quality of life (EORTC QLQ-30, CR29), and financial toxicity (COST-FACIT). Surveys were administered in REDCap at baseline and three months follow-up. The primary endpoint was survey completion; feasibility was assessed by recruitment, participation, and completion rates. Descriptive comparisons were made between EOCRC (<50 years) and average-age onset colorectal cancer (AOCRC; ≥50 years). RESULTS: From March 2024 to April 2025, 66 patients were approached, and 60 (91%) consented; all completed the baseline survey (100%), confirming feasibility across academic and safety-net settings. However, for the three-month follow-up survey participation decreased by 50%. The cohort was evenly distributed by sex (48% female, 52% male) and site (50% Parkland, 50% UTSW). Participants were diverse (42% Hispanic, 18% Black, 42% Non-Hispanic White) with variable socioeconomic status: 38% reported income <$35,000, 23% >$100,000, 28% were unable to work, and 23% were employed. Hospital utilization differed: 96% of Non-Hispanic Whites were treated at SCCC, while most Hispanic and Black patients were seen at PHHS. Parkland Financial Assistance was reported by 77%, highest among Hispanic patients. Nineteen patients (32%) had EOCRC (median age 42, range 30-48) and 41 (68%) had AOCRC (median age 64, range 51-82). EOCRC patients were more often Hispanic (58% vs. 32%), treated at Parkland (58% vs. 46%), and received assistance more frequently (47% vs. 34%). CONCLUSION: This pilot study confirms that comprehensive, survey-based data collection is feasible in a racially, ethnically, and financially diverse CRC cohort. These preliminary findings highlight the clinical and sociodemographic differences of EOCRC and AOCRC across distinct groups. Future work will expand longitudinal follow-up, incorporate electronic health record data, and leverage tumor registry phenotypes to enable low-touch, systematic patient recruitment for a more robust sample. Citation Format: Citlalli F. Lopez, L. Joseph Su, Luis Gonzalez, Yu-Lun Liu, Rasmi Nair, Lindsay Cowell, Emina Huang, Syed Mohammad Ali Kazmi. Feasibility of survey-based data collection in a diverse colorectal cancer cohort: Early-onset vs. average-onset [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 2357.

Background Doxorubicin (DOX)-based chemotherapy has improved survival outcomes in breast cancer patients but is often limited by doxorubicin-induced cardiotoxicity (DIC). Currently, no validated biomarkers can predict early DIC. Identifying novel biomarkers is essential for detecting patients at higher risk and enable timely interventions before irreversible cardiac injury occurs. Methods Twenty-seven breast cancer patients treated with DOX-containing chemotherapy were stratified by change in left ventricular ejection fraction (LVEF): 19 patients who maintained normal cardiac function (normal, decline < 10%) and 8 who developed cardiotoxicity (abnormal, decline > 10%). Plasma samples were collected at baseline and after chemotherapy for untargeted metabolomic profiling. Both baseline and pre-post designs were employed to capture static and dynamic metabolic alterations associated with DIC. Stepwise logistic regression was used to filter non-informative metabolites, and predictive performance was further validated using Random Forest modeling. Results A well-marked separation of plasma metabolomic profiles was observed between normal and abnormal cardiotoxicity groups at baseline (T0). Statistical analysis identified 100 significant metabolites at baseline (T0) and 78 metabolites after the first cycle of chemotherapy (T0-T1), with 10 metabolites common to both time-points: 3-phosphoglycerate, 2-hydroxyphenylacetate, inosine, taurine, suberate (C8-DC), sebacate (C10-DC), sphingadienine, oxindolylalanine. Machine learning models identified key metabolites (e.g., sebacate [C10-DC], 2-hydroxyhippurate, orotate, picolinate, and suberate [C8-DC]) as candidate predictors of cardiotoxicity, achieving moderate discriminatory performance in cross-validation, with higher specificity than sensitivity, indicating limited detection of abnormal cases. Conclusions Metabolomic profiling shows potential for early detection of DIC in breast cancer patients, supporting personalized interventions to prevent irreversible cardiac damage.

Background: Previous epidemiological studies on the associations between hazardous air pollutants (HAPs) and breast cancer (BC) have largely neglected rural, medically underserved areas in the United States, which differ in exposures and disparities compared to urban areas. Objectives: We aimed to examine the associations between carcinogenic HAPs and BC risk in a rural population. Methods: Using a nested case-control design, 574 cases and 2295 incidence density-sampled controls matched 1:4 on index age and race were included from the Arkansas Rural Community Health study. Twelve census-tract level HAPs from the 2005 National Air Toxics Assessment were geocoded to participants' baseline addresses and categorized into tertiles based on the control distributions. Multivariable conditional logistic regression analysis was used to estimate associations for BC and subgroups. Additionally, weighted quantile sum (WQS) regression was used to assess the effects of pollutant mixtures. Results: Adjusted models resulted in significantly increased risk of BC for moderate PAH (ORT2 = 1.32; 95% CI 1.03-1.69) and high chromium (ORT3 = 1.31; 95% CI 1.00-1.70, P trend = 0.04) exposure. The WQS index term, which is the regression coefficient of the combined pollutant mixture, was non-significantly positively associated with BC (OR = 1.21; 95% CI 0.96-1.53). Chromium (0.45), propylene dichloride (0.15), and polychlorinated biphenyls (0.09) were weighted the most, suggesting these pollutants had the greatest impact on the increased risk of BC. Joint effects models with first-degree family history of BC resulted in increased risk of BC for women with family history compared to women without family history and low PAH exposure. Conclusion: This study highlights significant associations between specific HAPs, particularly PAHs and chromium, and increased BC risk in a rural population, emphasizing the need for targeted public health interventions and regulatory efforts to mitigate exposure in medically underserved areas.

While anthracyclines, commonly used in cancer treatment, are well known to cause cardiotoxicity, no validated biomarkers currently exist that can predict the early development of doxorubicin-induced cardiotoxicity (DIC). Therefore, identifying early biomarkers of DIC is urgently needed. Metabolomics approaches have been used to elucidate this relationship and identified related metabolite markers. However, differences in pre-clinical model systems make it challenging to draw definitive conclusions from the discoveries and translate findings into clinical applications. A systematic literature search on metabolomics studies of DIC was conducted with the goal to identify and compare study results reported using in vitro models, animal models, and studies from clinical patients. Metabolites identified across all studies were pooled to uncover biologically meaningful patterns that are significantly enriched in the data. Finally, pooled metabolites perturbed by DIC were mapped to metabolic pathways to explore potential pathological implications. We reviewed 28 studies published between 2000 and 2024 that utilized metabolomics approaches to investigate DIC. The included studies used a variety of analytical techniques, including LC–MS, GC–MS, and NMR. The analysis revealed that metabolites such as inosine, phenylalanine, arginine, and tryptophan were commonly perturbed across all study models, with carnitine metabolism and purine and pyrimidine metabolism being the most affected pathways. Metabolite Set Enrichment Analysis (MSEA) using MetaboAnalyst identified the arginine biosynthesis, citrate cycle, and alanine, aspartate, and glutamate metabolism pathways as significantly enriched. These findings underscore the potential of metabolomics in identifying early biomarkers for DIC, providing a foundation for future studies aimed at preventing cardiotoxicity and improving treatment strategies for cancer patients receiving DOX-containing therapies. Altogether, metabolomics studies suggest metabolic alterations in DIC, albeit little overlap between studies especially with animal and human studies. Attempts at intercepting these pathways have shown that intervention in DIC may be possible. Future research should focus on developing precise cardiotoxicity models that incorporate cancer metabolism, as these will be crucial in bridging the gap between laboratories (in vitro and animal models) and clinical studies to identify subclinical biomarkers in the early stage of DIC that can effectively identify new targets for interventions to reduce lethal cardiovascular disease risk.

Objective To evaluate the impact of replacing a traditional midterm exam with a collaborative project-based assessment on student performance and engagement in an introductory graduate-level biostatistics course for public health students using R programming. Methods We conducted a retrospective study comparing 2 semesters of the same course at a US school of public health. In Fall 2023, students completed traditional midterm and final exams. In Fall 2024, the midterm exam was replaced with a structured project-based assessment, while the final exam format remained unchanged. Student performance was compared using midterm scores, final exam scores, overall course grades, and course evaluations. Additionally, we used the results of a postproject survey that students in the project-based cohort had completed to assess engagement, confidence, and satisfaction. Results Students in the project-based cohort (Fall 2024) had significantly higher and more consistent midterm scores (median 94.0 vs 91.1; P = . 01) and final exam scores (median 93.7 vs 86.0; P = . 03) than the exam-based cohort (Fall 2023). Final course grades were also higher and more consistent in the project- based cohort. Survey responses indicated high student satisfaction, improved confidence in data analysis and R programming, and increased appreciation for real-world applications. Students also identified challenges related to group dynamics and time management. Conclusion Replacing a traditional exam with a collaborative project-based assessment in biostatistics significantly improved student performance, engagement, and satisfaction. These findings support project-based learning as a valuable pedagogical strategy in public health education, particularly for developing applied data analysis skills with R.

African American (AA) men experience a 70% higher incidence and disproportionately aggressive forms of prostate cancer compared to European American (EA) men. Folate, critical for DNA synthesis and methylation, may influence cancer outcomes, especially in populations with distinct genetic and dietary profiles. We investigated the role of dietary folate intake and gene variants in folate metabolism in contributing to racial disparities in prostate cancer aggressiveness. Data from 1,497 prostate cancer cases (722 AA, 775 EA) from the North Carolina-Louisiana Prostate Cancer Project were analyzed. Dietary intakes of natural folate, synthetic folate, and dietary folate equivalents (DFE) were measured using validated food frequency questionnaires. SNPs in folate metabolism genes (rs758711/MTHFD1, rs4652/AGER, and MTHFR 677TT) were genotyped from blood samples. Multivariable logistic regression models assessed associations between folate intake, SNPs, and prostate cancer aggressiveness, stratified by race and adjusted for age, BMI, energy intake, education, smoking, screening history, and family history. AA men had higher folate intake and a significantly greater likelihood of high tumor aggressiveness (31.6% vs. 21.7% in EA, p<0.001). Among AA men, high intake of DFE (adjusted odds ratio (adjOR)=2.09), synthetic folate (adjOR=2.25), and natural folate (adjOR=2.19) were associated with increased odds of aggressive disease. These associations were attenuated or reversed in EA men. Genetically, AA men with the rs758711 CC variant exhibited greater increases in plasma folate at high synthetic folate intake. The rs4652 SNP showed a threshold effect in AA men, and MTHFR 677TT was linked to consistently lower plasma folate levels, particularly in AA men. Gene-diet interactions in folate metabolism may contribute to racial disparities in prostate cancer aggressiveness. Higher folate intake may elevate risk among genetically susceptible AA men. These findings highlight the need for ancestry-informed nutrition and cancer prevention strategies tailored to at-risk populations. L. Joseph Su, MinJae Lee, Ping-Ching Hsu. Racial disparities in folate metabolism, genetic variants, and prostate cancer aggressiveness [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 A064.

Significant racial disparities exist in prostate cancer (PCa), particularly among African American (AA) men, who consume fewer green vegetables and face prolonged environmental exposure such as arsenic. However, the role of DNA methylation in folate and arsenic metabolism in PCa formation and progression remains unclear, especially among AA men. Blood DNA methylation was analyzed in 117 PCa cases from the North Carolina-Louisiana Prostate Cancer Project (PCaP), including AAs and European Americans (EAs). PCa aggressiveness was classified using clinical stage, Gleason score, and PSA level. Plasma folate and folic acid were quantified and categorized into quartiles. Univariate and multivariate analyses assessed the effect of plasma folate and PCa aggressiveness on DNA methylation profiles, adjusting for age, race, smoking, urinary heavy metal concentrations, and cell compositions. Significant separation of DNA methylation profiles by race was observed at baseline. Variations in dietary folate, heavy metal exposure, cell compositions, and smoking histories significantly affected DNA methylation profiles. When examining the methylation changes associated with metal exposure and PCa aggressiveness, arsenic and cadmium showed significant interactions with aggressive PCa. Plasma folic acid had the most influence on DNA methylation profiles compared to unmetabolized folic acid and synthetic folates. Conclusions: Plasma folic acid levels interact with PCa aggressiveness, suggesting nutritional status is important to prevent aggressive outcomes in PCa. Additionally, arsenic exposure significantly contributes to the methylation profiles, highlighting the need to reduce arsenic exposure among high-risk populations. Ping-Ching Hsu, Se-Ran Jun, L. Joseph. Su. Modulation of DNA methylation by plasma folate and heavy metals in relation to prostate cancer aggressiveness [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 C089.

Abstract Objective: Early onset colorectal cancer (EO CRC) is rising at an alarming rate. While average onset colorectal cancer (AO CRC) affects patients mostly above 65 years of age, EO CRC affects patients under 50 years of age, disproportionately affecting males from low-income communities and racial/ethnic minorities. Chronic inflammation has been identified as a strong contributor to pathogenesis. We hypothesize that methylation of DNA may serve as a potential mechanism associated with chronic inflammation that contributes to the etiology differentially between EO and AO CRC. Methods: Formalin-fixed paraffin-embedded (FFPE) tissue specimens from four AO and EO CRC patients each were retrieved from the Tissue Repository. Paraffin curls containing tumor and adjacent normal tissues were generated from appropriate EO and AO CRC patient tissues. The Qiagen GeneRead DNA FFPE genomic DNA kit was then used to extract the DNA from the paraffin curls. Illumina Methylation EPIC v2.0 kit was used to evaluate DNA methylation (DNAm) patterns after the restoration process from deamination in the fixed/embedded sample using the Uracil-N-Glycosylase enzyme. Unreliable and non-specific probes were removed before statistical analysis for differentially methylated CpG sites. Age acceleration for each tissue was calculated by comparing the estimated DNAm age with chronological age using the Horvath approach. Results: A clear clustering of DNAm patterns by age of onset were observed for both normal and tumor tissues. However, there was no difference when comparing tumor and normal tissues after multiple corrections. Four-way ANCOVA adjusting for race, gender, BMI, and tissue type suggested that age onset was the most significant factor. We also found that age acceleration in EO CRC tissue is greater than in AO CRC. After applying Bonferroni correction, significant differentially methylated regions (DMRs) were found in the promoter and the gene body of SNTB1, NFATC3, SLC25A24, RABGAP1L, WDSUB1, WWOX, SELB, SLC28A3, and PPP6R2 in EO CRC patients when compared to AO CRC. SNTB1 regulates colorectal cancer progression and stemness, while NFATC3 has been associated with inflammation and cancer. Conclusions: The preliminary results from this study showed a significant difference in the DNAm profile of FFPE samples between AO and EO CRC. The finding suggests that epigenetics may play a role in the etiology of CRC, potentially involved in the chronic inflammation pathway. The analysis of a larger patient number is underway to strengthen these findings. Citation Format: L. Joseph Su, Ping-Ching Hsu, Aniruddha Rathod, Yulun Liu, Jacopo Ferruzzi, Syed Kazmi, Emina Huang. Distinct DNA methylation patterns between early-onset and average-onset colorectal cancer patients [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 7005.

Background:Outpatient parenteral antimicrobial therapy (OPAT) is a safe and cost-effective transitional care approach administered via different delivery models. No standards exist for appropriate OPAT program staffing. We examined outcomes of patients receiving OPAT via different care models to identify strategies to improve safety while reducing health care overuse.Methods:Retrospective demographic, clinical, and outcome data of patients discharged with OPAT were reviewed in 2 periods (April-June 2021 and January-March 2022; ie, when staffing changed) and stratified by care model: self-administered OPAT, health care OPAT, and skilled nursing facility OPAT.Results:Of 342 patients, 186 (54%) received OPAT in 2021 and 156 (46%) in 2022. Hospital length of stay rose from 12.4 days to 14.3 in 2022. In a Cox proportional hazards regression model, visits to the emergency department (ED) within 30 days of OPAT initiation (hazard ratio, 1.76; 95% CI, 1.13-2.73; P = .01) and readmissions (hazard ratio, 2.34; 95% CI, 1.22-4.49; P = .01) increased in 2022 vs 2021, corresponding to decreases in OPAT team staffing. Higher readmissions in the 2022 cohort were for reasons unrelated to OPAT (P = .01) while readmissions related to OPAT did not increase (P = .08).Conclusions:In a well-established OPAT program, greater health care utilization-length of stay, ED visits, and readmissions-were seen during periods of higher staff turnover and attrition. Rather than blunt metrics such as ED visits and readmissions, which are influenced by multiple factors besides OPAT, our findings suggest the need to develop OPAT-specific outcome measures as a quality assessment tool and to establish optimal OPAT program staffing ratios.

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.

Smoking is a modifiable lifestyle factor that has not been established as a prostate cancer risk factor, nor emphasized in prostate cancer prevention. Studies have shown that African American (AA) smokers have a poorer cancer prognosis than European Americans (EAs), while having a lower prevalence of heavy smoking. We examined the relationship between cigarette smoking and prostate cancer aggressiveness and assessed racial differences in smoking habits on the probability of high-aggressive prostate cancer. Using data from the North Carolina-Louisiana Prostate Cancer Project (n = 1,279), prostate cancer aggressiveness was defined as high or low based on Gleason scores, serum prostate-specific antigen levels, and tumor stage. Cigarette smoking was categorized as current, former, or never smokers. Multivariable logistic regression was used to estimate adjusted odds ratios (OR) and 95

Abstract Background. Doxorubicin (DOX) is a highly effective chemotherapy agent that is commonly used in combination with other chemotherapy regimens to treat a wide range of cancers, including 32% of breast cancer (BC) cases. Although DOX has greatly increased the number of long-term cancer survivors, some DOX recipients have experienced DOX-induced cardiotoxicity (DIC). Currently, there are no validated markers that can predict the early development of DIC. Cardiac troponin released by cardiomyocytes has been used in non-clinical studies as a marker of myocardial injury; however, the false positive rates are high, and the predictive value on cardiotoxicity is limited. Therefore, novel biomarkers of DIC are urgently needed to identify patients who are at an increased risk, allowing early detection of the cardiotoxicity before it causes permanent cardiac damage. Methods. Untargeted metabolomics profiling was performed for plasma samples from a cohort of 28 breast cancer patients who developed abnormal cardiac function (ABN) and those who maintained normal cardiac function (NML). Blood samples were collected before, during, and after DOX-containing chemotherapy. Using both baseline observations and pre-post changes, machine-learning techniques were used to identify metabolite markers that can be used as early indicators of DIC in BC patients. Area under the receiver operating characteristic curve was reported to evaluate the performance of significant metabolites, and metabolite set enrichment analysis (MSEA) and network analysis were used to extrapolate known associations between metabolites and diseases. Results. Significant separation of plasma metabolomics profiles between ABN and NML patients at baseline was observed. From 1,124 metabolites, abundance of 59 metabolites were found to differ between ABN and NML patients at baseline. Across all patients, levels of 78 metabolites changed between baseline and after the 1st chemotherapy cycle. Of the 6 metabolites identified in both baseline and pre-post data, ABN patients had higher levels of dicarboxylic acids suberate and sebacate derived from ω-oxidation of fatty acids at baseline than NML patients. Enrichment analysis on the metabolites from the pre-post analysis suggested myocardio injury and carnitine palmitoyltransferase deficiency. Network analysis of metabolite-disease interactions further suggests potential impact on neurological health after chemotherapy. Conclusion. The metabolomics phenotype identified is indicative of impaired beta-oxidation at baseline for ABN patients. In addition, our findings suggest neurotoxic effect from DOX, implicating the potential brain-heart axis involved behind the cardiotoxicity phenotype. Citation Format: Se-Ran Jun, Katherine Wallis, Reid D. Landes, Valentina K. Todorova, L. Joseph Su, Sam Makhoul, Ping-Ching Hsu. Metabolic phenotypes of doxorubicin-induced cardiotoxicity in breast cancer patients [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 3625.

Background/Objectives: The incidence of colorectal cancer (CRC) is rising, and Western diets high in red and processed meats may be contributing. It is important to identify dietary nutrients that increase CRC risk and perhaps interventions that may modulate such risk. The relationship between dietary choline intake and CRC is still unclear. We hypothesize that high dietary choline intake is associated with greater CRC risk, and B vitamin supplementation may modify this risk. Methods: In this case-control study, we collected demographic and dietary data using the validated National Cancer Institute CRC Risk Assessment Tool and Dietary Health Questionnaire III and analyzed colonoscopy outcomes. Logistic regression and stratified analyses were performed to calculate adjusted odds ratios and evaluate for effect modification. Results: Of 52 total patients, 21 had a normal colonoscopy result, and 31 were found to either have benign polyps or CRC. The average dietary choline intake was 207 mg/day in the normal group and 297 mg/day in the abnormal outcome group. A doubling in dietary choline intake was significantly associated with increased odds of polyps or CRC (OR 25.32, 95% CI 1.95-327.94). When stratified by vitamin B levels, the effect modification was difficult to confidently quantify due to the limited sample size. Conclusions: Our findings suggest that higher dietary choline intake may be associated with an increased risk of CRC and its precursors, such as polyps. Although the potential modifying role of B vitamins was inconclusive, this study underscores the need for larger-scale research to further explore these associations and to assess the potential of dietary interventions in reducing CRC risk.