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Background Human papillomavirus (HPV) vaccination is the most effective biomedical intervention for HPV infections. HPV vaccination rate among sexually active young adults is largely unknown. Methods Patients aged 18–26 years, who attended the Rhode Island Sexually Transmitted Infections Clinic between 2013–2018, were included in the study. We extracted demographics, behavioral characteristics, and HPV vaccination status from electronic medical records. Exploratory logistic regressions were conducted to identify factors associated with vaccination status. Results Among 2729 eligible individuals, the median age was 23 years (interquartile range: 22–25). Only 8.1% of males and 24.8% of females received at least one dose of HPV vaccine. Females were 144% (crude odds ratio [cOR]: 2.44, 95% confidence interval [CI]: 2.03, 2.94) more likely to receive at least one dose of HPV vaccine than males. Being Black/African American (B/AA) or Hispanic/Latino (H/L) was associated with a 21% (cOR: 0.79, 95% CI: 0.62, 1.00) and 34% (cOR: 0.66, 95% CI: 0.53, 0.81) decrease in the odds of vaccination, respectively. Conclusions HPV vaccination rate was low among sexually active young adults. Gender and racial/ethnic disparities existed in HPV vaccination. Interventions are needed to promote HPV vaccination among sexually active young adults, especially B/AA and H/L communities.

Folate, including the folic acid form, is a key component of the one-carbon metabolic pathway used for DNA methylation. Changes in DNA methylation patterns during critical development periods are associated with disease outcomes and are associated with changes in nutritional status in pregnancy. The long-term impact of periconceptional folic acid supplementation on DNA methylation patterns is unknown.To determine the long-term impact of periconceptional folic acid supplementation on DNA methylation patterns, we examined the association of the recommended dosage (400 μg/d) and time period (periconceptional before pregnancy through first trimester) of folic acid supplementation with the DNA methylation patterns in the offspring at age 14-17 y compared with offspring with no supplementation.Two geographic sites in China from the 1993-1995 Community Intervention Program of folic acid supplementation were selected for the follow-up study. DNA methylation at 402,730 CpG sites was assessed using saliva samples from 89 mothers and 179 adolescents (89 male). The mean age at saliva collection was 40 y among mothers (range: 35-54 y) and 15 y among adolescents (range: 14-17 y). Epigenome-wide analyses were conducted to assess the interactions of periconceptional folic acid exposure, the 5,10-methylenetetrahydrofolate reductase (MTHFR)-C677T genotype, and epigenome-wide DNA methylation controlling for offspring sex, geographic region, and background cell composition in the saliva.In the primary outcome, no significant differences were observed in epigenome-wide methylation patterns between adolescents exposed and those non-exposed to maternal periconceptional folic acid supplementation after adjustment for potential confounders [false discovery rate (FDR) P values 0.05]. The MTHFR-C677T genotype did not modify this lack of association (FDR P values 0.05).Overall, there were no differences in DNA methylation between adolescents who were exposed during the critical developmental window and those not exposed to the recommended periconceptional/first-trimester dosage of folic acid.

Background Most cervical cancers are directly linked to oncogenic or high-risk human papillomavirus (HR-HPV) infection. This study evaluates associations between diet quality and genital HPV infection in women. Methods This study included 10,543 women from the 2003–2016 National Health and Nutrition Examination Survey. The outcome was the genital HPV infection status (HPV-negative, low-risk [LR] HPV, and HR-HPV). Dietary quality was evaluated using the Healthy Eating Index (HEI), with which a higher score indicates a better diet quality. Results Women who are not consuming total fruits (15.8%), whole fruits (27.5%), or green vegetables and beans (43%) had a significantly higher risk of HR-HPV infection than women who complied with the Dietary Guidelines for Americans (HR-HPV OR = 1.76, 1.63 and 1.48 for a HEI score of 0 vs. 5) after adjusting confounding factors. Similar results of these food components on LR-HPV infection were shown. In addition, intake of whole grains and dairy was inversely associated with LR-HPV infection. Conclusions This study showed that women who did not eat fruits, dark-green vegetables, and beans had a higher risk of genital HR-HPV infection. Intake of these food components is suggested for women to prevent HPV carcinogenesis.

Supplemental Table 1 Supplemental Table 2

Patient and clinical characteristics of Caucasian and African American statin users and non-users.

Logistic regression analysis of associations between statin use and prostate cancer aggressiveness, additionally adjusted for education, income and family history of prostate cancer.

Background: Although statin use has been associated with reduced prostate cancer aggressiveness, the impact of race and patient characteristics on this association is not well understood. We examined the association between statin use and prostate cancer aggressiveness in Caucasians (CA) and African Americans (AA) and explored effect modification by health-seeking behaviors associated with statin use.Methods: Of 1,930 cases from The North Carolina-Louisiana Prostate Cancer Project, 344 (18%) were classified as aggressive based on clinical criteria. Utilizing nonaggressive cases as referent, logistic regression was used to examine the association between statin use and prostate cancer aggressiveness, overall and stratified by race. Smoking and prostate cancer screening were examined as effect modifiers of this association.Results: There was an inverse association between statin use and prostate cancer aggressiveness [OR, 0.74; 95% confidence interval (CI), 0.56–0.96], with comparable effect estimates in both races. Although not statistically significant, statin use was associated with reduced ORs for aggressive prostate cancer in never-screened men (OR, 0.79; 95% CI, 0.45–1.39), men screened at low/recommended frequency (≤once/year; OR, 0.66; 95% CI, 0.41–1.06), and men screened at high frequency (>once/year; OR, 0.78; 95% CI, 0.53–1.15). Inverse associations between statins and aggressive prostate cancer were strongest in never smokers (OR, 0.42; 95% CI, 0.25–0.72), attenuated in former smokers (OR, 0.84; 95% CI, 0.59–1.19), and absent in current smokers (OR, 1.36; 95% CI, 0.70–2.64).Conclusions: Statin use was associated with reduced prostate cancer aggressiveness in CA and AAs, with strongest inverse associations in nonsmokers.Impact: Health-seeking behaviors associated with statin use should be considered when examining the impact of statins on prostate cancer aggressiveness. Cancer Epidemiol Biomarkers Prev; 25(4); 670–7. ©2016 AACR.

Logistic regression analysis of associations between statin use and prostate cancer aggressiveness, excluding men using non-statin cholesterol-lowering drugs.

Background: Studies showed that folate and related single nucleotide polymorphisms (SNPs) could predict prostate cancer (PCa) risk. However, little is known about the interactions of folate-related SNPs associated with PCa aggressiveness. The study’s objective is to evaluate SNP–SNP interactions among the DHFR 19-bp polymorphism and 10 SNPs in folate metabolism and the one-carbon metabolism pathway associated with PCa aggressiveness. Methods: We evaluated 1294 PCa patients, including 690 European Americans (EAs) and 604 African Americans (AAs). Both individual SNP effects and pairwise SNP–SNP interactions were analyzed. Results: None of the 11 individual polymorphisms were significant for EAs and AAs. Three SNP–SNP interaction pairs can predict PCa aggressiveness with a medium to large effect size. For the EA PCa patients, the interaction between rs1801133 (MTHFR) and rs2236225 (MTHFD1), and rs1801131 (MTHFR) and rs7587117 (SLC4A5) were significantly associated with aggressive PCa. For the AA PCa patients, the interaction of DHFR-19bp polymorphism and rs4652 (LGALS3) was significantly associated with aggressive PCa. Conclusions: These SNP–SNP interactions in the folate metabolism-related genes have a larger impact than SNP individual effects on tumor aggressiveness for EA and AA PCa patients. These findings can provide valuable information for potential biological mechanisms of PCa aggressiveness.

Evidence regarding the association between income and risk of colorectal cancer (CRC) is inconclusive. Furthermore, the relationship between income dynamics and CRC risk among individuals with type 2 diabetes (T2D) is unknown. Using nationally representative data from the Korean Health Insurance Service database, 1,672,811 adults with T2D aged 30 to 64 years and without a history of cancer were enrolled between 2009-2012. We determined income levels based on 20 quantiles of monthly health insurance premiums and assessed income quartiles annually for five years preceding participant enrollment. Hazard ratios(HRs) and 95% confidence intervals(CIs) were estimated after adjusting for sociodemographic factors, CRC risk factors, and diabetes duration and treatment. During follow-up (median, 7.8 years), 22,149 CRC cases developed at least 1 year after enrollment. Individuals with sustained low income (i.e., lowest income quartile) over five years had increased CRC risk (HR 1.11, 95% CI 1.05-1.18). In contrast, those with sustained high income (i.e., highest income quartile) had decreased CRC risk (HR 0.81, 95% CI 0.73-0.89), which was more pronounced for rectal cancer (HR 0.64, 95% CI 0.52-0.78) and distal colon cancer (HR 0.70, 95% CI 0.57-0.86). Income declines (i.e., a decrease≥25% in income quantile) were associated with increased CRC risk (HR≥2 vs. 0 declines 1.10, 95% CI 1.05-1.16; p trend=0.0007). Among those with low income at 5 years pre-enrollment, CRC risk decreased linearly with increasing income levels over five years(p trend

Background. While anthracyclines are well known to cause cardiotoxicity, no validated biomarkers that can predict the early development of anthracycline-induced cardiotoxicity (AIC) currently exist. Therefore, early biomarkers of AIC are urgently needed. Metabolomics approaches have been used to elucidate this relationship. However, differences in pre-clinical model systems making it challenging to draw conclusions from the discoveries and translate into clinical development. Aim of Review. A systematic literature review on metabolomics studies of AIC in breast cancer was conducted with the goal to identify and compare study results reported using cell culture models, animal models, tumor-bearing animal models, and clinical patients. We further pooled metabolites identified from all studies to identify biologically meaningful patterns that are significantly enriched in the data. Lastly, pooled metabolites perturbed by AIC were mapped to metabolic pathways for potential pathological implications. Key Scientific Concepts of Review. Altogether, metabolomics studies suggest metabolic alterations in AIC, albeit little overlap between studies especially with breast cancer patients. Attempts at intercepting these pathways have shown that intervention in AIC may be possible. Optimal study design to accurately mimic the human breast cancer condition taking cancer metabolism into consideration will play key role to translate animal models to clinical studies to identify biomarkers in the early diagnosis of AIC and point to new targets for intervention.

In order to design a cancer prevention promotion program in the region, suggestions were solicited at a medical center. We hypothesized that a majority would be native to state, and would be able to articulate about the barriers that may exist. Through online survey and focus groups, suggestions were sought, and the knowledge and the compliance with cancer prevention recommendations were assessed to determine the participants' qualifications as potential educators. Sixty-five point two percent of participants (n = 1018) graduated from high school in Arkansas. The most commonly given suggestions were to provide education to increase awareness, to use social media for promotion, to improve access, and to reduce costs. Self-reported adherence rates to breast, cervical, and colorectal cancer screening were 82.6% (n = 954), 75.8% (n = 541), and 76.7% (n = 453), respectively. Having a personal history of cancer significantly increased colorectal cancer screening uptake (p = 0.04), but paradoxically decreased mammography uptake (p = 0.007). Salary of $40,000 and more and having a Bachelor's degree or higher were associated with higher compliance of Papanicolaou test only (p = 0.007 and p = 0.001, respectively). A majority (67.7%, n = 1056) of respondents expressed willingness to contribute to promoting cancer prevention measures, and 38.3% (n = 559) were willing to participate in focus groups. However, only 6.3% (n = 35) actually participated. The participants' knowledge and compliance appeared to be sufficient, but their follow through in focus group participation was poor.

BACKGROUND Studying the differential impact of aspirin and other nonsteroidal anti-inflammatory drugs across the stages of colorectal neoplasia from early adenoma to cancer is critical for understanding the benefits of these widely used drugs. METHODS With 13 years of follow-up, the authors prospectively evaluated the association between aspirin and ibuprofen use and incident distal adenoma (1221 cases), recurrent adenoma (862 cases), and incident colorectal cancer (CRC; 2826 cases) among men and women in the population-based Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. With multivariable-adjusted models, odds ratio (ORs) and 95% confidence intervals (CIs) for adenoma incidence and recurrence and hazard ratios (HRs) and 95% CIs for incident CRC were determined. RESULTS The authors observed a significantly reduced risk of incident adenoma with ibuprofen use (≥30 vs

The associations of testosterone therapy (TTh) and statins use with prostate cancer remain conflicted. However, the joint effects of TTh and statins use on the incidence of prostate cancer, stage and grade at diagnosis, and prostate cancer-specific mortality (PCSM) have not been studied. We identified White (N = 74,181), Black (N = 9,157), and Hispanic (N = 3,313) men diagnosed with prostate cancer in SEER-Medicare 2007–2016. Prediagnostic prescription of TTh and statins was ascertained for this analysis. Weighted multivariable-adjusted conditional logistic and Cox proportional hazards models evaluated the association of TTh and statins with prostate cancer, including statistical interactions between TTh and statins. We found that TTh (OR = 0.74; 95% CI, 0.68–0.81) and statins (OR = 0.77; 95% CI, 0.0.75–0.88) were inversely associated with incident prostate cancer. Similar inverse associations were observed with high-grade and advanced prostate cancer in relation to TTh and statins use. TTh plus statins was inversely associated with incident prostate cancer (OR = 0.53; 95% CI, 0.48–0.60), high-grade (OR = 0.43; 95% CI, 0.37–0.49), and advanced prostate cancer (OR = 0.44; 95% CI, 0.35–0.55). Similar associations were present in White and Black men, but among Hispanics statins were associated with PCSM. Prediagnostic use of TTh or statins, independent or combined, was inversely associated with incident and aggressive prostate cancer overall and in NHW and NHB men. Findings for statins and aggressive prostate cancer are consistent with previous studies. Future studies need to confirm the independent inverse association of TTh and the joint inverse association of TTh plus statins on risk of prostate cancer in understudied populations. Prevention Relevance: The study investigates a potential interaction between TTh and statin and its effect on incident and aggressive prostate cancer in men of different racial and ethnic backgrounds. These results suggest that among NHW and non-Hispanic Black men TTh plus statins reduced the odds of incident prostate cancer, high-grade and advance stage prostate cancer.

Both arsenic and cadmium are reported to be toxic to humans. The use of saliva as a biomarker of low-level exposures to these elements has not been adequately explored, and the putative relationship between exposure and obesity is unclear. This cross-sectional study aims to investigate the relationship between salivary arsenic and cadmium concentrations and their association with obesity. Arsenic and cadmium concentrations were analyzed in human saliva samples by Inductively Coupled Plasma-Mass Spectrometry on 270 randomly selected women who participated in the Arkansas Rural Community Health Study. Multivariable logistic regression was performed to evaluate the association between heavy metal concentrations and obesity. Stratified logistic regression was performed based on menopausal status. Generalized linear models were used to evaluate weight gain velocity. Significant positive associations were observed in postmenopausal women for both arsenic (OR = 4.43, 95% CI 1.91–10.28) and cadmium (OR = 2.72, 95% CI 1.23–5.99) concentrations, as well as significant trends among tertiles (p p = 0.01, respectively). No relationship with obesity was evident among premenopausal women for either metal. A dose–response relationship was observed between increasing weight gain velocity and increasing metal concentrations. At concentrations well below governmental and industrial standards for acute toxicity, significant associations between obesity and concentration of these heavy metals are evident. The rate at which individuals gain weight is affected by metal concentrations and may play a role in the rapid increase in weight in postmenopausal women. These results might explain, in part, the missing variability in the increasing obesity pandemic in certain population exposed to these environmental toxicants.

Introduction: Accelerated aging is associated with lifetime stress and frailty, and has been reported in aging-related disease and mortality, including lung cancer, postmenopausal breast cancer, childhood cancer, and coronary heart disease. However, current knowledge on the impact of epigenetic aging in anti-tumor immunity remains limited. Pre-existing immune status heavily contributes to cancer diagnosis and the success of immunotherapy treatment, therefore, the relationship between epigenetic aging and immune function, and how it may lead to racial health disparity needs to be further explored. Methods: Genome-wide DNA methylation analysis were conducted in a feasibility test of 16 participants with equal number of African Americans (AAs) and European Americans (EAs), and epigenetic age (mAge) were calculated using R package methylclock for the established multi-tissue epigenetic clock algorithms which consists of 353 CpGs by Horvath. Correlation analysis was performed between mAge and in vitro T cell activation tests. Results: As expected, high correlation of calculated mAge versus chronological age was observed from 16 participants using the Horvath calculator, with higher mAge in AAs than EAs. Significant separation in DNA methylation profiles between AAs and EAs existed based on the top 1,000 CpG sites from the principal component analysis. To understand the effects of aging on T cell function, a series of functional assays were performed from different age groups, and significant (P Citation Format: Ping-Ching Hsu, Michael Bauer, Tung-Chin Chiang, Lora J. Rogers, A. Murat Aydin, L. Joseph Su, Brian Koss. Racial differences in epigenetic aging and its impact on expression of T-cell inhibitory receptors [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr B015.

Objective: Results of studies examining the association between intake of meat or fish and prostate cancer have been mixed. However, few of the previous studies have included a racially diverse population or focused on aggressive prostate cancer. We aimed to examine the association between intake of meat and fish 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: Meat and fish intakes in the year prior to diagnosis were estimated using an interviewer-administered modified version of the National Cancer Institute Diet History Questionnaire in 909 Black and 991 White men with a recent 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 tertile of meat and fish intake variables, with adjustment for age, energy intake, race, study site, education, family history of prostate cancer, prostate cancer screening history, Charlson comorbidity index, NSAIDs use, smoking status, alcohol intake, and intake of vegetables, fruits, and milk. Results: We observed increased odds of aggressive prostate cancer among men in the second tertile compared to the first tertile for total red meat (OR:1.23. 95% CI: 0.91 – 1.68) and unprocessed red meat (OR:1.30. 95% CI: 0.96 – 1.76), though confidence intervals were imprecise and associations in the top tertile were weaker. For processed meat, a non-statistically significant increased odds of aggressive prostate cancer was observed among men in the third tertile compared to the first tertile (OR:1.27. 95% CI: 0.91 – 1.78). ORs for higher intake of fish and poultry were in the inverse direction but were weak and not statistically significant. Conclusions: In this racially diverse case-only study, we observed weak positive associations between red and processed meat and aggressive prostate cancer, and little evidence of an association with fish or poultry intake. While high temperature cooking and charring of meat is known to increase carcinogen formation, one limitation of our study was the lack of information on cooking methods or doneness of the meat consumed. Additional research is warranted among racially diverse populations that considers cooking methods and doneness preferences. Citation Format: Jessica Sainyo, Susan E. Steck, L. Joseph Su, Lenore Arab, Jeannette T. Bensen, Elizabeth T.H. Fontham, James L. Mohler. Associations between meat and fish intake and aggressive prostate cancer in the North Carolina-Louisiana Prostate Cancer Project (PCaP). [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P035.

To examine associations between recreational and occupational physical activity and prostate cancer aggressiveness in a population-based, case-only, incident prostate cancer study.Data were analyzed from the cross-sectional North Carolina-Louisiana Prostate Cancer Project of African-American (n = 1,023) and European-American (n = 1,079) men newly diagnosed with prostate cancer (CaP). High-aggressive CaP was defined as Gleason sum ≥ 8, or prostate-specific antigen 20 ng/ml, or Gleason sum ≥ 7 and clinical stage T3-T4. Metabolic equivalent tasks (MET) were estimated from self-reported recreational physical activity in the year prior to diagnosis assessed retrospectively via a validated questionnaire and from occupational physical activity based on job titles. Associations between physical activity variables and high-aggressive prostate cancer were estimated using logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for multiple confounders.There was suggestive evidence that walking for 75-150 min/week for exercise is associated with lower odds of high-aggressive prostate cancer compared to no walking (OR = 0.69, 95% CI 0.47-1.01). Physical activity at the current job was associated with 24% lower odds of high-aggressive prostate cancer (highest vs. lowest tertile OR = 0.76, 95% CI 0.56-1.04). However, total MET-h/week of recreational physical activity and accumulation of high-level physical activity at the longest-held job were not associated with high-aggressive prostate cancer. Results did not vary by race.The odds of high-aggressive prostate cancer were lower among men who walk for exercise and those engaged in occupations with high activity levels.

Background African-American (AA) men tend to present with more aggressive prostate cancer (Gleason score >7) than European-American (EA) men. Vitamin D and its metabolites are implicated in prostate cancer biology with vitamin D deficiency, indicated by its metabolite levels in serum or plasma, usually observed in AA men. Objective To determine if 1, 25-dihydroxy vitamin D3 [1,25(OH)2 D] plasma levels in AA and EA prostate cancer patients alter the risk of having aggressive prostate cancer. Design Research subjects from the North Carolina-Louisiana Prostate Cancer Project (AA n = 435 and EA n = 532) were included. Plasma metabolites 1,25(OH)2 D and 25-hydroxyvitamin D3 [25(OH)D] were measured using liquid chromatography with tandem mass spectrophotometry. Research subjects were classified into low (Gleason sum 8 or Gleason sum = 7 with 4 + 3, or PSA > 20 ng/mL, or Gleason sum = 7 and stage T3-T4) aggressive disease. Results Research subjects in the second and third tertiles of plasma levels of 1, 25(OH)2 D had lower odds of high aggressive prostate cancer (AA [ORT2vsT1 : 0.66, 95%CI: 0.39-1.12; ORT3vsT1 : 0.83, 95%CI: 0.49-1.41] and EA [ORT2vsT1 : 0.68, 95%CI: 0.41-1.11; ORT3vsT1 : 0.67, 95%CI: 0.40-1.11]) compared with the first tertile, though confidence intervals included the null. Greater 1,25(OH)2 D/25(OH)D molar ratios were associated with lower odds of high aggressive prostate cancer more evidently in AA (ORQ4vsQ1 : 0.45, CI: 0.24-0.82) than in EA (ORQ4vsQ1 : 0.64, CI: 0.35-1.17) research subjects. Conclusions The 1,25(OH)2 D/25(OH)D molar ratio was associated with decreased risk of high aggressive prostate cancer in AA men, and possibly in EA men. Further studies analyzing vitamin D polymorphisms, vitamin D binding protein levels, and prostatic levels of these metabolites may be useful. These studies may provide a better understanding of the vitamin D pathway and its biological role underlying health disparities in prostate cancer.

Educational print materials for young women breast cancer survivors (YBCS) are supplemental tools used in patient teaching. However, the readability of the text coupled with how well YBCS understand or act upon the material are rarely explored. The purpose of this study was to assess the readability, understandability, and actionability of commonly distributed breast cancer survivorship print materials. We used an environmental scan approach to obtain a sample of breast cancer survivorship print materials available in outpatient oncology clinics in the central region of a largely rural Southern state. The readability analyses were completed using the Flesch-Kincaid (F-K), Fry Graph Readability Formula (Fry), and Simple Measure of Gobbledygook (SMOG). Understandability and actionability were analyzed using Patient Education Materials Assessment Tool for Printable Materials (PEMAT-P). The environmental scan resulted in a final sample of 14 materials. The mean readability of the majority of survivorship materials was "difficult," but the majority scored above the recommended 70% in both understandability and actionability. The importance of understandability and actionability may outweigh readability results in cancer education survivorship material. While reading grade level cannot be dismissed all together, we surmise that patient behavior may hinge more on other factors such as understandability and actionability. Personalized teaching accompanying print material may help YBCS comprehend key messages and promote acting upon specific tasks.

Background: Smoking has not been an established risk factor for prostate cancer (PCa), and has not been emphasized in PCa prevention. However, recent studies have shown increasing evidence that there is a higher risk of biochemical recurrence, PCa mortality, and metastasis among current smokers, presenting an urgent need in re-evaluating the association between smoking and aggressive PCa. This study aimed to determine whether smoking increase the likelihood of developing a more aggressive prostate cancer. Methods: Equal numbers of African Americans (AAs) and European Americans (EAs) by smoking status (never/former/current) matched with PCa aggressiveness, BMI, 5-year age group, and year of baseline recruitment, totaling 480 participants, were included in the metabolomics study. For metabolomics analysis, fold change and BH-adjusted p-value from t-test adjusted for age for univariate analysis, and PCA adjusted for age and PLS-DA supervised statistical analysis for multivariate analysis were employed to decipher the underlying metabolomic patterns, and identify significantly dysregulated metabolites for the variables of interest. Results: AA participants were significantly younger (mean=61.4, SD=7.7) compared with EAs (mean=63.5, SD=7.5). Current smokers had a 2.4 times higher risk of high aggressive PCa. When stratified by race, the risk diminished for EAs but increased for AAs. Global metabolic profiles detected a total of 1,487 compounds of known identity. After excluding metabolites with missing values in more than 20% of the samples and with small standard variation, we observed a distinct cluster of participants from AA aggressive PCa patients and current smokers that were separated from EAs and never smokers. With BH-adjusted p-value < 0.05 and fold change > 2, we identified 10 significantly dysregulated metabolites between AA and EA among high aggressive PCa and current smokers. Further, 36 metabolites between current and never smokers among AA high aggressive PCa were significantly dysregulated, but none of them are annotated as tobacco metabolites. Conclusion: Our study presented distinctive metabolomics profiles specific to AA current smokers who had high aggressive PCa. Furthermore, the distinctive patterns were not driven by the tobacco metabolites, with the potential to identify metabolites that might help to understand the relationships between smoking and aggressive PCa in AA. Citation Format: Se-Ran Jun, L. Joseph Su, Eryn Matich, Ping-Ching Hsu. Distinctive metabolomics profiles associated with African American current smokers who have high aggressive prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3680.

Background: DNA methyltransferases (DNMTs) control DNA methylation and impact gene expression. Many studies have demonstrated that genetic variants in DNMT genes play a role in cancer development, including breast cancer. However, the impact of SNP-SNP interactions for DNMTs associated with breast cancer risk is unclear. The objective is to evaluate SNP-SNP interactions associated with breast cancer risk. Methods: We selected 14 SNPs in 3 DNMT genes (DNMT1, DNMT3A, and DNMT3B) for the 4,195 women (1:2 match for breast cancer cases and controls), including 1,085 African Americans (AAs) and 3,110 European Americans (EAs) in the Arkansas Rural Community Health (ARCH) cohort. We included different inheritance models (dominant, recessive, and additive) for individual SNP effects, using logistic regressions with breast cancer status (yes/no) as the outcome. Two-way SNP-SNP interactions associated with breast cancer risk were analyzed using the SNP Interaction Pattern Identifier (SIPI) approach developed by our research team. Results: Out of the 14 DNMTs SNPs, we found two SNPs (rs7605753 and rs10196635 in DNMT3A) were individually associated with breast cancer risk (p Conclusion: Our findings support that the SNPs in DNMT genes play an essential role in breast cancer risk. SIPI is an excellent tool to evaluate SNP-SNP interactions, which can better predict breast cancer risk. Citation Format: Hui-Yi Lin, L. Joseph Su, Lora J. Rogers, Gail A. Runnells, Ping-Ching Hsu, Shelbie D. Stahr, Tung-Chin Chiang. Interactions of DNMTs genetic variants associated with breast cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1450.

Doxorubicin (DOX)-induced cardiotoxicity is a major limitation to its clinical application. Cardiotoxicity of DOX is dose-dependent that begins with the first dose. Oxidative stress and inflammation are involved in DOX-related cardiotoxicity. This study aimed to determine whether multiple markers of inflammation, hypercoagulability and endothelial injury correlate with the risk of early DOX-induced cardiotoxicity in breast cancer patients. Blood samples of 51 breast cancer patients treated with DOX-based chemotherapy were collected before (baseline) and after the first cycle of chemotherapy. The risk of cardiotoxicity was defined as an asymptomatic reduction of cardiac left ventricle ejection fraction (LVEF) >10% at completion of chemotherapy versus baseline. Plasma samples were examined for multiple biomarkers of inflammation, hypercoagulability and endothelial dysfunction, including C-reactive protein (CRP), thrombomodulin (TM), thrombin-antithrombin complex (TAT), myeloperoxidase (MPO), von Willebrand factor (vWF) and P-selectin. Surrogate markers of neutrophil extracellular traps (NETs) nucleosomes and double stranded DNA (dsDNA) were also measured. Patients with abnormal decline of LVEF >10% (n=21) had significantly elevated levels of MPO and TM both at baseline, and after the first dose of DOX-based chemotherapy relative to patients with normal LVEF (n=30) after adjusting for race, age, BMI and type of breast cancer. The first dose of DOX also induced significantly higher circulating levels of TAT complex and nucleosomes in patients at risk of cardiotoxicity in comparison with patients without. The comparison between the means of the biomarkers in after-before DOX-based chemotherapy of the two groups of patients showed significant differences for MPO, TAT complex and CRP. The results from this study suggest that the risk of DOX-induced cardiotoxicity in breast cancer is associated with endothelial dysfunction, inflammation and prothrombotic state before and after the first dose of chemotherapy.

Background Calcium and dairy product intakes have been positively associated with prostate cancer risk. An imbalance in concentrations of calcium and magnesium has been associated with multiple chronic diseases, although few studies have examined the relation with prostate cancer aggressiveness. Objective The goal of this study was to examine the association between dietary intakes of calcium and magnesium, the calcium-to-magnesium ratio (Ca:Mg), and dairy products and prostate cancer aggressiveness. Design Dietary intake was assessed with the use of an interviewer-administered modified National Cancer Institute Diet History Questionnaire in 996 African American and 1064 European American men with a recent histologically confirmed diagnosis of prostate cancer from the North Carolina-Louisiana Prostate Cancer Project (PCaP). High-aggressive disease was defined as Gleason sum ≥8, or prostate-specific antigen (PSA) >20 ng/mL, or Gleason score ≥7 and clinical stage T3-T4. The comparison group was all other prostate cancer cases. Logistic regression was used to determine the adjusted ORs and 95% CIs for high-aggressive prostate cancer by tertile of diet and supplement exposures. Results There was a positive association across tertiles of dietary Ca:Mg intake, with odds of high-aggressive prostate cancer in the upper tertiles as follows-OR for tertile 2 compared with tertile 1: 1.38 (95% CI: 1.01, 1.88); OR for tertile 3 compared with tertile 1: 1.46 (95% CI: 1.06, 2.02). When stratified by race, the positive association was more pronounced in African American men (OR for tertile 3 compared with tertile 2: 1.62; 95% CI: 1.04, 2.53). Men who reported the highest daily consumption of whole-fat milk had a 74% increased odds of high-aggressive prostate cancer compared with non-whole-fat milk drinkers, which was attenuated after adjustment for potential mediating factors, such as saturated fat and Ca:Mg intake. Conclusions Among both African American and European American men diagnosed with prostate cancer, a higher Ca:Mg and whole-milk intake were associated with higher odds of high-aggressive prostate cancer. This study was registered at www.clinicaltrials.gov as NCT03289130.

BACKGROUND: Statin use is associated with lower advanced prostate cancer risk and reduced prostate cancer-specific mortality, but prior studies were conducted mainly in white men. We examined the effect of statin use on risk of prostate cancer progression in a population-based, minority-enriched cohort.METHODS: We used data from prostate cancer cases (45% African American) diagnosed between 2004 and 2007 who participated in the Health Care Access and Prostate Cancer Treatment in North Carolina cohort (HCaP-NC). We abstracted statin use at diagnosis. Men reported if they had ever been diagnosed with high cholesterol. Multivariable Cox proportional hazards analysis was used to examine associations between statin use and risk of prostate cancer progression (biochemical recurrence or secondary treatment), overall and by race. In secondary analysis, we examined the association between high cholesterol and risk of progression, overall, and by statin use.RESULTS: Of 669 men, 244 (36%) were statin users at diagnosis. During 3.8 years median follow-up, 138 men experienced prostate cancer progression. There was no association between statin use and risk of progression, either overall (HR 1.03; 95%CI 0.72-1.46) or stratified by race. High cholesterol was inversely associated with risk of progression, particularly among statin users (HR 0.43; 95%CI 0.20-0.94; p-interaction = 0.22) and in men with higher perceived access to care (HR 0.57; 95%CI 0.36-0.90; p-interaction = 0.03). Study limitations included a relatively small sample size, short follow-up, and lack of data regarding post diagnosis statin use.CONCLUSIONS: Statin use at diagnosis was not associated with prostate cancer progression in the population-based, minority-enriched HCaP-NC. Greater healthcare engagement, including actively controlling serum cholesterol, may be linked to better prostate cancer-specific outcomes.

IMPACT: Our results reveal a limited amount of breast cancer survivorship print materials as both understandable and actionable, and indicate a need to supplement material with personalized teaching. OBJECTIVES/GOALS: Using educational print material for young women breast cancer survivors (YBCS) is considered a best practice in patient teaching. Little is known about how well YBCS understand or act upon the material. The purpose of this study was to assess the understandability and actionability of commonly distributed breast cancer survivorship print materials. METHODS/STUDY POPULATION: We used an environmental scan approach to obtain breast cancer survivorship print materials available in eight outpatient oncology clinics and one electronic medical record used in a Midwestern state. Print materials were included if they were freely available to patients, were specific to breast cancer, provided detailed information about survivorship, and were directly given to patients by physicians or nurses. Print materials were excluded if topics were related to treatment, diagnosis, or prevention. All brochures, drug advertisements, and advertisements for support services were excluded. The understandability and actionability analyses of the breast cancer survivorship print materials were analyzed using Patient Education Materials Assessment Tool for Printable Materials (PEMAT-P). RESULTS/ANTICIPATED RESULTS: The environmental scan resulted in 82 individual print materials. After applying the inclusion and exclusion criteria, eight breast cancer survivorship print materials were included in the final sample. The final sample included two books, two patient education handouts from the electronic medical record, two multi-page booklets, and two pamphlets. The overall mean understandability score of the print materials was 68.9% ? 11.3 with a range of 47% to 80%. Five materials scored above the recommended 70% in understandability. The overall mean actionability score of the print materials was much higher at 81.3% ? 21.6 with a range of 67% to 100%. Five materials scored above 70% in actionability. However, only three of the eight materials scored above the recommended 70% in both understandability and actionability. DISCUSSION/SIGNIFICANCE OF FINDINGS: Limited breast cancer survivorship print materials exist as both understandable and actionable. Personalized instruction provided by oncology team members may be indicated to supplement the material. This additional teaching may help ensure survivors comprehend messages and act upon specific tasks as indicated in survivorship print material.

Pacific Islanders face many health disparities, including higher rates of cardiovascular disease, cancer, obesity, and diabetes compared to other racial and ethnic groups. Specifically, the Marshallese population suffers disproportionately from type 2 diabetes, with rates 400% higher than the general US population. As part of an ongoing community-based participatory research (CBPR) partnership, 148 participants were recruited for a study examining genetic variants to better understand diabetes. Participants provided a saliva specimen in an Oragene® DNA self-collection kit. Each participant provided approximately 2 mL volume of saliva and was asked qualitative questions about their experience. The study yielded a recruitment rate of 95.5%. Among the 148 persons who participated, 143 (96.6%) agreed to be contacted for future studies; 142 (95.9%) agreed to have their samples used for future IRB-approved studies; and 144 (97.3%) gave permission for the researchers to link information from this study to other studies in which they had participated. Qualitative responses showed that the majority of participants were willing to participate because of their desire to contribute to the health of their community and to understand the genetic influence related to diabetes. This study demonstrates willingness to participate in genetic research among Marshallese living in Arkansas. Willingness was likely enhanced because the feasibility study was part of a larger CBPR effort. This study is important to community stakeholders who have voiced a desire to collaboratively conduct genetic research related to diabetes, perinatal outcomes, and cancer.

OBJECTIVES/GOALS: Young women (18 – 45 years of age) with breast cancer have complex medical and psychosocial needs. Educational materials are often used as tools in patient-centered communication. However, these materials disseminate complex health information in print-heavy formats and can be difficult to understand for women with varying health literacy levels. METHODS/STUDY POPULATION: In the first phase of this study, the principal investigator (PI) will recruit 40 diverse women to participate in four focus groups (FG) to explore the perceived usefulness of the most frequently used cancer educational materials. The PI will also obtain demographics and heath literacy levels of the FG participants using the Newest Vital Sign. In the second phase, the PI will assess the literacy demands of the ten most frequently used cancer educational print materials and five most frequently used websites described by the FG participants. The perceptions of the usefulness of materials and the literacy demands will then be used to appraise the effectiveness of materials within patient-centered cancer communication. RESULTS/ANTICIPATED RESULTS: Results from this study will provide a patient-centered blueprint that will be used to design more effective educational materials that treatment centers can incorporate into their patient-centered cancer communication process. The next step of this research will be to determine providers’ perceptions of cancer education materials used to exchange information within the patient-centered communication process. This will complement the patient findings and inform the development of the provider aspect of a communication intervention centered on designing educational materials for women with various health literacy levels within the patient-centered cancer communication process. DISCUSSION/SIGNIFICANCE OF IMPACT: Detecting the usefulness of cancer educational materials, as perceived by young women with breast cancer, is foundational to developing communication interventions that improve cancer outcomes. This study will identify how materials can be improved in the critical informational-exchange component of the patient-communication process.

Objectives: Rural women are underrepresented in cancer research. We hypothesized that providing access to a research study to rural, medically underserved women who were receiving their breast cancer screening using a mobile mammography unit would increase the representation of rural women in a cancer cohort study. Design: This study is a cross-sectional study using a cohort of women who have been recruited to a breast cancer study in Arkansas. Setting: Recruiters accompanied a mobile mammography unit, the MammoVan, to implement a novel method for reaching and recruiting underrepresented rural Arkansas women into the study. Participants include 5850 women recruited from 2010 through 2012 as part of the Arkansas Rural Community Health (ARCH) study. Results: Participants recruited during their mammography screening on the MammoVan tended to be more rural, less educated, and more likely to be non-Hispanic than those recruited in other venues. A significant difference was not noted for race or age. Conclusion: Collaboration with the MammoVan greatly aided the recruitment of rural participants. These strategies can facilitate the representation of this historically underserved and understudied rural population in future research studies.

INTRODUCTION AND OBJECTIVES:Active surveillance (AS) or definitive treatment (DT) in the form of surgery and radiation are treatment options for low risk prostate cancer (Pca). However, quality of ...

Background Studies investigating the association between pesticide exposure and colorectal cancer (CRC) risk have been inconclusive. Objectives Investigate the association between pesticide exposure and CRC risk through a systematic literature review. Methods CRC has the fourth-highest rate of cancer-caused death in the US after lung cancer, breast cancer in women, and prostate cancer in men. Here we have conducted a systematic literature search on studies examining the association between any pesticide exposure and CRC risk using PubMed, MEDLINE via EBSCO host, and Embase according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Results Following the review, 139 articles were included for qualitative evaluation. Study participants were farmers, pesticide applicators, pesticide manufacturers, spouses of pesticide applicators, farm residents, Korean veterans of the Vietnam War, rural communities, and those who consumed food with pesticide residues. The studies' results were split between those with significant positive (39 significant results) and inverse (41 significant results) associations when comparing pesticide exposure and CRC risk. Discussion From our literature review, we have identified a similar number of significant positive and inverse associations of pesticide exposure with CRC risk and therefore cannot conclude whether pesticide exposure has a positive or inverse association with CRC risk overall. However, certain pesticides such as terbufos, dicamba, trifluralin, S-ethyl dipropylthiocarbamate (EPTC), imazethapyr, chlorpyrifos, carbaryl, pendimethalin, and acetochlor are of great concern not only for their associated elevated risk of CRC, but also for the current legal usage in the United States (US). Aldicarb and dieldrin are of moderate concern for the positive associations with CRC risk, and also for the illegal usage or the detection on imported food products even though they have been banned in the US. Pesticides can linger in the soil, water, and air for weeks to years and, therefore, can lead to exposure to farmers, manufacturing workers, and those living in rural communities near these farms and factories. Approximately 60 million people in the US live in rural areas and all of the CRC mortality hotspots are within the rural communities. The CRC mortality rate is still increasing in the rural regions despite the overall decreasing of incidence and mortality of CRC elsewhere. Therefore, the results from this study on the relationship between pesticide exposure and CRC risk will help us to understand CRC health disparities.

Background: Although statin use has been associated with reduced prostate cancer aggressiveness, the impact of race and patient characteristics on this association is not well understood. We examined the association between statin use and prostate cancer aggressiveness in Caucasians (CA) and African Americans (AA) and explored effect modification by health-seeking behaviors associated with statin use. Methods: Of 1,930 cases from The North Carolina-Louisiana Prostate Cancer Project, 344 (18%) were classified as aggressive based on clinical criteria. Utilizing nonaggressive cases as referent, logistic regression was used to examine the association between statin use and prostate cancer aggressiveness, overall and stratified by race. Smoking and prostate cancer screening were examined as effect modifiers of this association. Results: There was an inverse association between statin use and prostate cancer aggressiveness [OR, 0.74; 95% confidence interval (CI), 0.56–0.96], with comparable effect estimates in both races. Although not statistically significant, statin use was associated with reduced ORs for aggressive prostate cancer in never-screened men (OR, 0.79; 95% CI, 0.45–1.39), men screened at low/recommended frequency (≤once/year; OR, 0.66; 95% CI, 0.41–1.06), and men screened at high frequency (>once/year; OR, 0.78; 95% CI, 0.53–1.15). Inverse associations between statins and aggressive prostate cancer were strongest in never smokers (OR, 0.42; 95% CI, 0.25–0.72), attenuated in former smokers (OR, 0.84; 95% CI, 0.59–1.19), and absent in current smokers (OR, 1.36; 95% CI, 0.70–2.64). Conclusions: Statin use was associated with reduced prostate cancer aggressiveness in CA and AAs, with strongest inverse associations in nonsmokers. Impact: Health-seeking behaviors associated with statin use should be considered when examining the impact of statins on prostate cancer aggressiveness. Cancer Epidemiol Biomarkers Prev; 25(4); 670–7. ©2016 AACR.

Introduction: Prostate Cancer (PCa) disproportionately affects African Americans, as AA men are more commonly diagnosed with aggressive PCa and twice as likely to have mortality from the disease compared to European Americans (EA). The one- carbon metabolism pathway has been extensively studied for cancer development, yet little research has been reported on its association with aggressiveness of cancer at diagnosis. The purpose of our study is to determine whether there is difference by race for the impact of a DHFR 19bp polymorphism together with multiple single nucleotide polymorphisms (SNPs) in one-carbon metabolism genes on a cohort of men diagnosed with either low-aggressive or high-aggressive PCa. Methods: DNA samples from a population-based study of 1,498 PCa subjects in the North Carolina- Louisiana Prostate Cancer Project were analyzed. The DHFR 19bp polymorphism was targeted by utilizing two TaqMan TAMRA probes, one with a FAM fluorescent probe to identify the insertion allele and one with a VIC fluorescent probe to identify the deletion allele. Six SNPs were genotyped via TaqMan SNP genotyping assays by Applied Biosystems. Chi-Square analyses were performed to examine differences in genotype between race. A multivariable logistic regression model adjusted for confounders was utilized to estimate the association of the 19bp DHFR polymorphism and one-carbon metabolism SNPs with PCa aggressiveness. Results: A total of 152 participants were excluded due to insufficient DNA samples, resulting in a sample of 1,346 participants. The analysis consisted of 993 low-aggressive and 345 high aggressive PCa cases. Chi-square analyses revealed significant frequency differences between AAs and EAs for the 19bp DHFR deletion polymorphism (31.2% vs 17.6%), as well as MTHFR rs1801131, MTHFR rs1801133, MTR rs1805087, MTHFD1 rs2236225, and MTHFD2 rs7587117 (P values < 0.0001). After adjusting for confounders, the cohort was stratified based on DHFR polymorphism status. Among subjects with the 19bp DHFR double deletion, individuals with heterozygous MTR rs1805087 (AG) were significantly less likely to have aggressive PCa (OR = 0.27 [0.10, 0.74]) when compared to individuals with the GG genotype. Among the group that had at least one copy of wild-type DHFR, heterozygous individuals (GA) at MTHFD1 rs2236225 had a significantly lower chance of aggressive PCa diagnosis (OR = 0.60 [0.38, 0.95]) compared to individuals with the AA genotype. Conclusion: Substantial differences exist between AAs and EAs in regard to polymorphisms within the one-carbon metabolism pathway. There appears to be significant interaction among genes involved that can be attributable to the racial distribution of genetic polymorphisms. Studies examining the association between folate metabolism and PCa should consider the modulation effect of gene-gene interaction when analyzing the polymorphisms collectively. Citation Format: C. Tyler Ratliff, Lora J. Rogers, L. Joseph Su. Racial differences in the association of one-carbon metabolism polymorphisms and prostate cancer aggressiveness [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-161.

Background. Significant racial disparities exist in PCa, with the incidence in African- Americans (AAs) being 50% higher than European Americans (EAs) and PCa mortality rates in AAs being more than two-fold higher. However, the disparity cannot be explained by screening, access to treatment, and genetics can only partially explain the disparity that does little to confer actionable clinical relevance. Currently, only 3 definitive risk factors for PCa have been identified: age, race, and family history of PCa. Smoking has not been an established risk factor for prostate cancer (PCa), and has not been emphasized in PCa prevention. However, recent studies have shown increasing evidence that there is a higher risk of biochemical recurrence, PCa mortality, and metastasis among current smokers, presenting an urgent need in re- evaluating the association between smoking and aggressive PCa. This study aimed to determine whether smoking increase the likelihood of developing a more aggressive prostate cancer. Methods. The study used data from the North Carolina–Louisiana Prostate Cancer Project (PCaP), which is a population-based study of incident PCa conducted between years 2004-2009 in 2 southern states where significant racial disparities in PCa are observed. Because PCa is over diagnosed and most PCa is not clinically relevant, this study will include only subjects with high (Gleason score ≥ 8; PSA > 20 ng/mL; Gleason score = 7 and stage T3–T4) or low (Gleason score < 7 and stage T1–T2 and PSA From the analysis, more AAs (57.6%) and those who were current smokers (22.7%) were diagnosed with high aggressive PCa. Current smokers had a 2.4 times- higher risk of high aggressive PCa (unadjusted OR=2.42, adjusted OR=2.39); when stratified by race, the risk diminished for EAs (OR=1.30) but increased for AAs (OR=3.36). Conclusion. Our study shows increased risk of aggressive PCa for current smokers, especially among AAs. Previous study had shown that self-reported cigarettes per day predicts smoke intake more poorly in AAs than in EAs. Thus, there is an urgent need in validated research using biomarkers to confirm the relationship of smoking and aggressive PCa, since cigarette smoking is preventable but have not been emphasized in PCa prevention. Citation Format: Ping-Ching Hsu, Shelbie Stahr, Christopher Brazeal, Elizabeth H. Fontham, L. Joseph Su. Smoking as a risk factor for the aggressive prostate cancer for African-American men from the North Carolina–Louisiana Prostate Cancer Project (PCaP) [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-201.

Background: Colorectal cancer (CRC) is the third leading cause of cancer death in the United States (US) but can be prevented with routine screening. A significant racial disparity exists among African Americans (AAs) with higher CRC incidence and mortality rates than other races, in particular in some rural areas, such as the lower Mississippi Delta regions including 17 counties in Arkansas. However, this disparity cannot be explained solely by lack of screening. Previous studies have suggested that this health disparity may be related to limited access to healthy food, lack of physical activity, and lack of facilities for cancer screening. Additional research in Arkansas is needed on the determinants of these disparities to develop actionable prevention strategies. Methods: An engagement approach known as a community review board (CRB) was used in this study. A CRB is a one-time meeting with community member experts who have personal experience with the research issue, and these experts provide feedback on the study. Two CRBs consisting of AAs age 45-75 were conducted, in urban, central (Little Rock, n=6) and rural, lower Delta (Helena, n=10) Arkansas communities, to better understand these communities’ perspectives on CRC and screening. We also discussed the community members’ willingness to participate in a study to look at the association between diet and food security with CRC and the barriers to participate. Differences in the viewpoints of the two CRBs were compared and documented. Results: Both rural and urban CRB respondents indicated their willingness to believe and listen to other community members, and generally do not go to the doctor unless they are sick. A lower percentage of our rural CRB participants (30%) had been screened for CRC as compared to our urban CRB participants (83%). When invited to participate in research studies, rural CRB respondents preferred to learn about the results of the study in a public, community forum. These older AA community members, both rural and urban, thought communities could benefit from more information disseminated related to these topics. Additionally, the rural CRB participants were more comfortable discussing CRC incidence and mortality with family compared to urban CRB participants. Conclusions: From this study, those in this rural community are more comfortable discussing CRC in the community-based discussion and with their family, and this may be related to the fact that they live in a CRC mortality hotspot in the Delta region. In addition, because members of these communities, both rural and urban, mentioned the need for more available information about CRC and screening we will hold virtual community forums with residents of Little Rock and Phillips County to discuss CRC, screening, and diet to inform and learn more from these Arkansas communities. We will also use the community members’ feedback to improve our research project in which we will analyze the association between food security, diet, and CRC. Citation Format: Eryn K. Matich, Rachel Hale, Nicola Spencer, M. Kathryn Stewart, L. Joseph Su, Ping-Ching Hsu. Colorectal cancer health disparity among African Americans: A qualitative study at the community level, exploring the connection between low access to resources, diet, and colorectal health [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-038.

UV exposure-induced oxidative stress is implicated as the driving mechanism of melanoma development. Increased oxidative stress results in imbalanced reactive oxygen species (ROS) that damage DNA and dysregulated epigenetic modifications and leads to melanoma progression. Sulforaphane (SFN) is the natural bioactivated product of the cruciferous vegetable family (e.g., broccoli and Brussels sprouts) and is known to play a dual role in cytoprotection and to induce apoptosis in the tumor via antioxidant regulation and histone modification of epigenetic enzymes. We investigated the combinational effect of 5-aza-2’-deoxycytidine (DAC), an FDA-approved DNA-modification epigenetic drug and SFN in melanoma cells. We found further cell growth inhibition and an increased number of altered gene expression profiles, increased survival-related cytokine expression, as well as unique histones post-translational modifications (PTMs) upon combinational treatments compared to single treatment in vitro. These results set the stage for animal studies. The long-term goal of the current study is to find an optimal dietary dose of antioxidants from SFN to reduce the burden of oxidative stress, which may contribute to melanoma recurrence, a constant problem with current treatments. In addition to recurrence, a reduced dose of epigenetic drugs applied may minimize the side effects of single-high-dose treatment. Citation Format: Tung-chin Chiang, L. Joseph Su, Brian S. Koss, Charity Washam, Stephanie Byrum, Aaron Storey, Alan J. Koss. Combinational effect of sulforaphane (SFN) and epigenetic demethylation agent 5-aza-2’-deoxycytidine (DAC) on metastatic melanoma [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr B26.

Background: Doxorubicin (DOX)-induced cardiotoxicity is cumulative-dose-dependent that begins with the first dose, but epigenetic changes after the first dose have not been examined. This study had two aims: Aim 1: to examine whether DNA methylation profile of peripheral blood cells (PBCs) induced by the first cycle of DOX-based chemotherapy can predict the risk of cardiotoxicity; and Aim 2 to determine if there are pretreatment methylation signatures at baseline to predict the risk of cardiotoxicity. Methods: Whole-genome DNA methylation of PBCs from 19 breast cancer patients was examined prior to the start of DOX-based chemotherapy and after the first cycle using Infinium HumanMethylation 450 BeadChip. ChAMP R package was used for the data normalization by the BMIQ algorithm and the COMBAT algorithm to adjust for batch effects. Chemotherapy-induced cardiotoxicity was determined by the assessment of left ventricle ejection fraction (LVEF) with multigated acquisition (MUGA) scan before chemotherapy and at its completion, and any LVEF decline by >10% was considered abnormal. Results: Pre- and post- DOX treatment were compared between patients with abnormal LVEF decline and those who maintained normal LVEF to assess the differences in the cytosine methylation states. The multiple correction testing resulted in a total of 515 differentially methylated CpGs between the patients with abnormal versus normal LVEF post-DOX treatment. There were 379 differentially methylated CpGs at baseline and 136 CpGs after the first cycle which significantly correlated with LVEF status after applying the Holm-Bonferroni method for multiple testing correction. The intersection of the probes resulted in 38 differentially methylated genes (DMG) that when used in hierarchical clustering, correctly clustered baseline samples into those that would result in normal and abnormal LVEF after treatment. DMG genes included SEPT5, IRF6, KCNQ1, NELL1, SIX6, HOXC9 and BCAN. IRF6, which encodes interferon regulatory factor 6, was identified as being significant in the subsequent analysis at the probe and region level. Comparisons of the samples before and after DOX treatment did not result in any probes associated with the treatment that were significant after multiple testing correction. Conclusions: The results from this study provide evidence that DNA methylation profile of peripheral blood cells has the potential to predict the risk of DOX-induced cardiotoxicity. The important finding was that the extent of methylation at baseline correlated with the post-DOX LVEF reduction, indicating that it may have the potential to predict the subsequent development of cardiotoxicity. Further studies with larger cohort of patients are needed to confirm these findings as well as narrowing down candidate methylation markers that can be implemented in a blood test. These finding may help guide treatment or identify patients that need to be followed closely to mitigate heart damage after DOX treatment. Citation Format: Michael A. Bauer, Issam Makhoul, Ping-Ching Hsu, Jeanne Wei, L. Joseph Su, Annjanette Stone, Weleetka Carter, Valentina K. Todorova. Genome-wide DNA methylation signatures predict the early asymptomatic doxorubicin-induced cardiotoxicity in breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-174.

UV exposure-induced oxidative stress is implicated as a driving mechanism for melanoma. Increased oxidative stress results in DNA damage and epigenetic dysregulation. We previously found that a low dose of the antioxidant sulforaphane (SFN) in combination with the epigenetic drug 5 –aza –2 ′–deoxycytidine (DAC) slowed cell growth in melanoma at a greater rate than DAC alone. Here, we report a multi –omics analysis with combination and single drug treatment. We observed a significant increase in global protein abundance with an altered level of expression in the combination treatment as compared to individual treatment. Proteins associated with methylation patterns and with reactive oxidative species were found dysregulated in combination treatment. A comparison analysis of proteomic and transcriptomic data with Ingenuity Pathway Analysis showed common canonical pathways involved in phosphorylation (ERK/MAPK signaling) and immune response with combination treatment. The global DNA methylation pattern was analyzed to explore the impact of combination and single drug treatment on methylation status. Interestingly, we observed an increase in the levels of a critical immuno-regulator cytokine, C –C motif ligand 5 (CCL5), which functions as a chemoattractant for natural killer (NK) cells. Animal studies showed the level of CCL5in blood and tumor was increased with DAC and SFN combination treatment compared to that of control, which coincided with tumor reduction. Our data demonstrate the impact of SFN on the effectiveness of the FDA –approved drug DAC to reduce metastatic melanoma tumors. Citation Format: Tung-Chin Chiang, Brian Koss, Aaron J. Storey, Jovanny Zabaleta, Samrat Roy Choudhury, Bradley D. Shields, Elizabeth C. Draper, L Joseph Su, Alan J. Tackett. Combination of sulforaphane and 5-aza-2′-deoxycytidine slows the growth and upregulates the chemoattractant CCL5 in metastatic melanoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-182.

Introduction and Purpose: DNA methylation is a potential biomarker of cellular stress and biologic aging, above that of chronologic age. Aberrant DNA methylation patterns have been associated with overall health and life expectancies and can be susceptible to biologic and environmental influences and stressors. DNA methylation has been shown to be modified by adverse living conditions in urban neighborhoods, but there is little knowledge of how adverse rural environments impact these biomarkers. An algorithm has been developed and validated that quantifies epigenetic age, and this measure has been strongly associated with health and life expectancy but has not been explored in rural and rural minority populations who have documented overall health disparities. The goal of this pilot study is to examine the impact of adverse rural neighborhoods on biomarkers of DNA methylation and epigenetic aging. Methods: Genome-wide DNA methylation was assessed using the Illumina 850K EPIC Beadchip, and the DNA methylation age estimation was derived using the algorithms Horvath developed based on the DNA methylation levels. Percent poverty rate at the census level was obtained according to their zip code data by ArcGIS. Ten women of self-reported African American (AA) descent each from counties with high poverty rates (>20% of the population) and those with low poverty rates ( Results: Among AA women, hypermethylation was more common in AA residents of counties with low compared to high poverty rates (70% vs 30%). The top canonical pathways impacted by differential methylation were related to glucocorticoid receptor, p53, and estrogen-dependent breast cancer signaling in AA women. EA women living in low-poverty counties exhibited less hypermethylation of CpGs than those living in high-poverty counties (27% vs. 73%). The top canonical pathways were related to hereditary breast cancer, glucocorticoid receptor, androgen and PI3K/AKT signaling. Epigenetic age of the 39 women in the study was highly correlated with their chronologic age (r=0.82, p=1.71e-10). When epigenetic age acceleration was considered, however, no significant differences by race and/or poverty levels were apparent. Conclusions: The finding of this pilot study suggests that living in adverse neighborhoods may impact DNA methylation patterns in breast cancer-related pathways when compared to living in affluent ones, and the pattern appears to be different on race. Larger studies should confirm our findings. Citation Format: Ping-Ching Hsu, Susan Kadlubar, Daniel Acheampong, Lora Rogers, Gail Runnells, Pearl McElfish, Mario Schootman, L. Joseph Su. Racial differences in genome-wide DNA methylation profiles by county poverty levels among women residing in Arkansas [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C062.

Background Environmental contamination with heavy metals, such as metalloid arsenic (As), cadmium (Cd), and chromium (Cr), in soil in the Mississippi River Delta region has been documented by the US Geological Survey. Rural residents are more likely to be exposed throughout their life than those who live in urban cities because much of the vegetation grown in this area has a potentially higher content of these heavy metals. At the same time, this region also experiences higher breast cancer (BC) disparity when compared to the other parts of the country. Mammographic density (MD) is one of the strongest risk factors for nonfamilial BC and it is also related to long-term prospective increases in tumor incidence, independent of its masking effects on detection. High MD thus is directly related to breast carcinogenesis. Methods Urine samples and lifestyle factors were obtained from a subcohort of women recruited through a mobile mammography unit into the Arkansas Rural Community Health Study cohort. Mammography at enrollment is available on everyone in this subcohort. Urinary samples were analyzed for heavy metal exposure, including As, Cd, and Cr concentration using Fisher-Thermo inductively coupled plasma mass spectrometry (ICP-MS). All samples were analyzed in duplicates and concentrations were presented as microgram/gram creatinine. Mammographic density was assessed by staff radiologist based on the American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) and verified with the LIBRA software, developed by the University of Pennsylvania. MD was categorized as dichotomous high (C and D) and low (A and B). Multivariable logistic regression was used to calculate odds ratios (OR) and 95% confidence interval (CI). Results Among 189 subjects who have completed follow-up interviews and contributed blood and urine samples, wee analyzed urine samples for heavy metal concentration, adjusted for urinary creatinine value and specific gravity. The mean (standard deviation) concentration of Cr, As and Cd were 0.27 (0.04), 0.28 (0.38) and 0.13 (0.11) ppb, respectively. We evaluated the association between MD and three major heavy metals of interest. When comparing the highest tertile urine Cr to the lowest tertile, Cr is positively associated with high MD (OR = 5.50, 95%CI = 1.08, 27.98) after adjusting for age, BMI, race, education, hormonal use, age at menarche, age at last menstrual cycle, and family history of breast cancer. Urine As is also positively associated with high MD (OR = 2.39, 95%CI = 0.98, 5.87, p = 0.06), adjusted for age and BMI. Cd was not significantly associated with MD with the current sample size. Conclusion Cr, As, and Cd are considered as Group 1 carcinogens according to the International Agency for Research on Cancer. This study suggests that there is a significantly increased odds of high MD even at very low levels of exposure to environmental Cr and As. Identifying sources of these contaminants would reduce the risk of breast cancer in rural communities. Citation Format: L. Joseph Su, Tung-Chin Chiang, Lora J Rogers, Gail A Runnells, Susan A Kadlubar, Zoey Crystal, Christopher Wardell, Sharp Malak. Association between high mammographic density and environmental chromium and arsenic exposure in a pilot study of women living in rural communities [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D097.

Background: Health-related quality of life (HRQOL) is multidimensional and is composed of, at a minimum, self-perceived health status, physical functioning and psychological well-being. HRQOL measures reflect the extent of disability and dysfunction associated with a chronic disease such as cancer. Self-perceived health status is a good proxy for disease burden among cancer patients. Purpose: This study used a nationally representative population survey to examine socioeconomic status disparities in HRQOL among survivors of thyroid, colon, lung, cervical, breast, prostate or ovarian cancer. Methods: Data from the 2009 Behavioral Risk Factor Surveillance System (BRFSS) survey conducted by the CDC were used to examine factors associated with HRQOL among participants reported ever having been diagnosed with cancer. Typically, the cancer survivorship module is an optional component of the survey. However, the 2009 survey considered the cancer survivorship questions to be a core or required component of the survey. The BRFSS is a cross-sectional survey that assessed overall HRQOL, self-perceived health status, number of bad physical health and bad mental health days per month. Least square regression and logistic regression models, adjusting for confounding variables (e.g., age, gender, race/ethnicity, education level, and number of comorbidities), were used for ordinal and dichotomous (5 (bad) vs 1-4 (excellent, very good, good, fair)) scale of HRQOL, respectively. Results: Among 432,607 surveyed, 59,173 reported ever been diagnosed with cancer. The seven most reported cancers were the focus of this study. Mean score for self-perceived health status (5-point scale) among survivors of thyroid, colon, lung, cervical, breast, prostate, and ovary was 2.83 (1.10), 3.15 (1.12), 3.68 (1.12), 2.98 (1.17), 2.93 (1.09), 2.94 (1.10), and 3.16 (1.18), respectively. After adjusting for confounders, a positive dose-response effect was observed between income level and all three HRQOL measures across all seven cancer sites. Income was consistently and inversely associated with a higher chance for reporting poorer HRQOL [OR: 0.64, 95% CI: 0.57-0.71], [OR: 0.63, 95% CI: 0.48-0.82], [OR: 0.67, 95% CI: 0.56-0.80], [OR: 0.69, 95% CI: 0.56-0.86], [OR: 0.55, 95% CI: 0.49-0.62], [OR:0.55, 95% CI: 0.44-0.69], [OR: 0.75, 95% CI: 0.62-0.91] among those with breast, thyroid, colon, lung, cervical, prostate, breast, and ovarian cancer, respectively. Race or ethnicity was not associated with in HRQOL among cancer survivors in the adjusted models. Conclusion: This study found income, but not race or ethnicity, is associated with HRQOL among cancer survivors, after adjusting for confounders in this nationally representative survey population. Household income appears to be a strong predictor of HRQOL among cancer survivors. Despite potential survival bias in this cross-sectional survey, it is possible that financial resources may lessen the overall burden of cancer survivors. Citation Format: Sarah N. O'Connor, L. Joseph Su. Self-perceived health status, poor physical and mental health days among cancer survivors with different socioeconomic status [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B036.