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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.

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 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.

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.

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: 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.

The purpose of this study was to determine the relationship between total antioxidant capacity (TAC) from diet and supplements and prostate cancer aggressiveness among 855 African Americans (AA) and 945 European Americans (EA) in the North Carolina-Louisiana Prostate Cancer Project (PCaP). Cases were classified as either high aggressive, low aggressive, or intermediate aggressive. TAC was calculated from the vitamin C equivalent antioxidant capacity of 42 antioxidants measured via food frequency questionnaire. EA reported greater dietary TAC from diet and supplements combined (P0.0001). In both minimally and fully adjusted logistic regression models, TAC from diet and supplements combined was associated with a reduced odds of high aggressive prostate cancer in all men, AA and EA: odds ratios for highest vs. lowest level (1500 vs.500 mg vitamin C equivalent/day): 0.31 [95% confidence interval (CI): 0.15, 0.67; P-trend0.01], 0.28 (95% CI: 0.08, 0.96; P-trend0.001), and 0.36 (95% CI: 0.15, 0.86; P-trend = 0.58), respectively. These associations did not appear to differ between AA and EA. These data suggest that greater intake of antioxidants is associated with less aggressive prostate cancer. Additional research is needed to confirm these results and determine the underlying mechanisms.

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.

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.

Neoadjuvant chemotherapy is given before surgery to patients with primarily unresectable, advanced-stage cancers to render the tumor resectable, and to facilitate breast conservation. Previously, we have reported a prospective phase II trial for women with stage IIA-B/IIIA-B-C breast cancer with improved pathologic complete response (pCR) when using bevacizumab in the neoadjuvant setting. Chemotherapy agents are given intravenously during multiple cycles of systemic treatments. However, the effect of the treatment is only evaluated upon the completion of therapy. Here, data from a clinical trial of 40 breast cancer patients with very aggressive disease and poor prognosis were studied aiming to identify epigenetic signatures in blood-derived DNA at baseline as potential non-invasive markers to predict pCR and to determine if treatment-related changes in epigenetic profiles reflect responsiveness to therapy. We performed genome-wide DNA methylation profiling using blood-derived DNA, and found that pre-treatment methylation status of BRD9 was predictive of responsiveness to therapy. Post-treatment global methylation differences were also observed between responders and non-responders. Most differentially methylated (DM) CpGs were located in promoter CpG-island regions for responders and in the open-sea region for non-responders. In responders, DNMT3B was hypomethylated while most of the other genes were hypermethylated after 4 cycles of treatment. Hypomethylation of DNMT3B could potentially lead to the increased methylation of oncogenes and genes responsible for cell growth and proliferation, facilitating responsiveness to the therapy. These results support the possible development of BRD9 as a biomarker for treatment selection before neoadjuvant therapy with chemotherapy and bevacizumab, and indicate DNMT3B as a potential target to improve clinical response. Further prospective validation of these findings is warranted. Trial registration ClinicalTrials.gov Identifier: NCT00203502.

Objectives Body composition alterations occur during aging. The purpose of the present analysis was to explore the functional consequences of the overlap of sarcopenia and osteoporosis, and the potential role of insulin-like growth factor 1 (IGF1) in their development in the oldest old. Setting and Participants Eighty-seven nonagenarians from the Louisiana Healthy Aging Study were included. Measures The definition of sarcopenia was based on appendicular lean mass (ALM). Osteoporosis was diagnosed based on bone mineral density (BMD) T score. Four phenotypes were compared: (1) healthy body composition, that is, nonosteoporotic nonsarcopenic (CO, control group), (2) osteoporotic (O, low BMD T score), (3) sarcopenic (S, low ALM), and (4) osteosarcopenic (OS, low BMD T score and low ALM). Sex- and age-specific IGF1–Standard Deviation Scores (SDS) were calculated. The Continuous Scale–Physical Functional Performance (CS-PFP) test was performed. Results In OS men, IGF1-SDS values (−0.61 ±0.37 vs −0.04 ± 0.52, P = .02) were lower than those in CO males (control group), whereas IGF1-SDS were similar in the 4 body composition phenotypes in women. In men only, ALM was positively associated with IGF1-SDS values (P = .01) independent of age and C-reactive protein concentration. Regarding bone health, we found no association between IGF1-SDS values and BMD. IGF1-SDS was not associated with functional performance (CS-PFP) in men and women. Conclusions/Implications IGF1 sensitivity in skeletal muscle and bone may differ by sex in the oldest old. IGF1 status did not appear to affect physical functionality. Determinants and clinical and functional characteristics of osteosarcopenia need to be further investigated in order to define conclusive diagnostic criteria.

Background Controversies remain over the safety and efficacy of vitamin E (i.e., α-tocopherol) supplementation use for the prevention of prostate cancer (CaP); however, associations of different tocopherol forms and CaP aggressiveness have yet to be examined. Methods This study examined whether food intake of tocopherols, vitamin E supplement use, and adipose tissue biomarkers of tocopherol were associated with CaP aggressiveness among African-American (AA, n = 1,023) and European-American (EA, n = 1,079) men diagnosed with incident CaP. Dietary tocopherols were estimated from a food frequency questionnaire, supplement use from questionnaire/inventory, and biomarkers from abdominal adipose samples measured using high-performance liquid chromatography. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were estimated from logistic regression comparing high-aggressive CaP to low/intermediate aggressive CaP, adjusting for covariates. Results Dietary intakes of α-and δ-tocopherol were related inversely to CaP aggressiveness among EAs [OR (95%CI), highest versus lowest quartile: α-tocopherol, 0.34 (0.17–0.69), Ptrend = 0.006; δ-tocopherol, 0.45 (0.21–0.95) Ptrend = 0.007]. Inverse associations between dietary and supplemental α-tocopherol and CaP aggressiveness were observed among AAs, though these did not reach statistical significance [OR (95%CI), highest versus lowest quartile: dietary α-tocopherol, 0.58 (0.28–1.19), Ptrend = 0.20; supplemental α-tocopherol, 0.64 (0.31–1.21) Ptrend = 0.15]. No significant association was observed between adipose tocopherol levels and CaP aggressiveness [OR (95%CI), highest versus lowest quartiles of α-tocopherol for EAs 1.43 (0.66–3.11) and AAs 0.66 (0.27–1.62)]. Conclusions The inverse associations observed between dietary sources of tocopherols and CaP aggressiveness suggests a beneficial role of food sources of these tocopherols in CaP aggressiveness. Prostate 75:1419–1435, 2015. © 2015 Wiley Periodicals, Inc.

Background. Prostate cancer is the most common noncutaneous cancer and second leading cause of cancer-related mortality in men in the US. Growing evidence suggests that oxidative stress is involved in prostate cancer.Methods. In this study, thioredoxin 1 (Trx 1), an enzyme and subcellular indicator of redox status, was measured in prostate biopsy tissue from 55 men from the North Carolina-Louisiana Prostate Cancer Project. A pathologist blindly scored levels of Trx 1. The association between Trx 1 and the Gleason score, erythrocyte antioxidant enzyme activity, and dietary antioxidant intake was determined using Fisher’s exact test.Results. Trx 1 levels in benign prostate tissue in men with incident prostate cancer were positively associated with the Gleason score (P=0.01) and inversely associated with dietary antioxidant intake (P=0.03). In prostate cancer tissue, Trx 1 levels were associated with erythrocyte glutathione peroxidase activity (P=0.01). No association was found for other erythrocyte enzymes. Greater Gleason score of malignant tissue corresponds to a greater difference in Trx 1 levels between malignant and benign tissue (P=0.04).Conclusion. These results suggest that the redox status of prostate tissue is associated with prostate cancer grade and both endogenous and exogenous antioxidants.

Bisphenol A (BPA) is an environmental estrogen used in the manufacture of polycarbonate plastics and epoxy resins used to make food and beverage packaging. Increasing evidence suggests that BPA mimics estrogens in the body and may be associated with putative markers of breast cancer risk.We analyzed the National Health and Nutrition Examination Survey (NHANES) 2003-2010 data to investigate the association of BPA with age at menarche in adolescent girls. We hypothesized that urinary BPA, as a surrogate biomarker for BPA exposure, is associated with earlier age at menarche, and that body mass index (BMI) may modulate this association.We conducted cross-sectional analyses of urinary BPA, BMI and age of menarche in a subsample of 987 adolescent girls aged 12-19, using pooled data from the 2003-2010 NHANES. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) for the association between urinary BPA and early onset of menarche, with adjustment for sampling design. We additionally assessed interaction of BPA with BMI.Adolescent girls with moderate BPA levels appeared to be less likely to have early onset of menarche than those with the lowest levels (OR=0.57; 95% CI=0.30, 1.08) after adjusting for age, race/ethnicity, parental education, country of birth, NHANES cycle, BMI and creatinine. BMI appeared to modify the BPA-menarche association.Although a non-significant trend suggests increasing urinary BPA may be associated with delayed menarche in adolescent girls, these results are based on cross-sectional data. Results should be clarified in carefully designed longitudinal cohort studies.

Epigenetics is emerging as an important field in cancer epidemiology that promises to provide insights into gene regulation and facilitate cancer control throughout the cancer care continuum. Increasingly, investigators are incorporating epigenetic analysis into the studies of etiology and outcomes. To understand current progress and trends in the inclusion of epigenetics in cancer epidemiology, we evaluated the published literature and the National Cancer Institute (NCI)–supported research grant awards in this field to identify trends in epigenetics research. We present a summary of the epidemiologic studies in NCI's grant portfolio (from January 2005 through December 2012) and in the scientific literature published during the same period, irrespective of support from the NCI. Blood cells and tumor tissue were the most commonly used biospecimens in these studies, although buccal cells, cervical cells, sputum, and stool samples were also used. DNA methylation profiling was the focus of the majority of studies, but several studies also measured microRNA profiles. We illustrate here the current status of epidemiologic studies that are evaluating epigenetic changes in large populations. The incorporation of epigenomic assessments in cancer epidemiology studies has and is likely to continue to provide important insights into the field of cancer research. Cancer Epidemiol Biomarkers Prev; 23(2); 223–33. ©2013 AACR.

Background: UV exposure-induced oxidative stress is implicated as a driving mechanism for melanoma. Increased oxidative stress results in DNA damage and epigenetic dysregulation. Accordingly, we explored whether a low dose of the antioxidant sulforaphane (SFN) in combination with the epigenetic drug 5-aza-2&rsquo, deoxycytidine (DAC) could slow melanoma cell growth. SFN is a natural bioactivated product of the cruciferous family, while DAC is a DNA methyltransferase inhibitor. Methods: Melanoma cell growth characteristics, gene transcription profiles, and histone epigenetic modifications were measured after single and combination treatments with SFN and DAC. Results: We detected melanoma cell growth inhibition and specific changes in gene expression profiles upon combinational treatments with SFN and DAC, while no significant alterations in histone epigenetic modifications were observed. Dysregulated gene transcription of a key immunoregulator cytokine&mdash, C-C motif ligand 5 (CCL-5)&mdash, was validated. Conclusions: These results indicate a potential combinatorial effect of a dietary antioxidant and an FDA-approved epigenetic drug in controlling melanoma cell growth.

Low unit response rates can increase bias and compromise study validity. Response rates have continued to fall over the past decade despite all efforts to increase participation. Many factors have been linked to reduced response, yet relatively few studies have employed multivariate approaches to identify characteristics that differentiate respondents from nonrespondents since it is hard to collect information on the latter. We aimed to assess factors contributing to enrollment of prostate cancer (PCa) patients. We combined data from the North Carolina-Louisiana (LA) PCa Project's LA cohort, with additional sources such as US census tract and LA tumor registry data. We included specific analyses focusing on blacks, a group often identified as hard to enroll in health-related research. The ability to study the effect of Hurricane Katrina, which occurred amidst enrollment, as a potential determinant of nonresponse makes our study unique. Older age (≥ 70) for blacks (OR 0.65) and study phase with respect to Hurricane Katrina for both races (OR 0.59 for blacks, OR 0.48 for whites) were significant predictors of participation with lower odds. Neighborhood poverty for whites (OR 1.53) also was a significant predictor of participation, but with higher odds. Among blacks, residence in Orleans parish was associated with lower odds of participation (OR 0.33) before Katrina. The opposite occurred in whites, with lower odds (OR 0.43) after Katrina. Our results overall underscore the importance of tailoring enrollment approaches to specific target population characteristics to confront the challenges posed by nonresponse. Our results also show that recruitment-related factors may change when outside forces bring major alterations to a population's environment and demographics.

BACKGROUND Associations between carotenoid intake and prostate cancer (CaP) incidence have varied across studies. This may result from combining indolent with aggressive disease in most studies. This study examined whether carotenoid intake and adipose tissue carotenoid levels were inversely associated with CaP aggressiveness. METHODS Data on African-American (AA, n = 1,023) and European-American (EA, n = 1,079) men with incident CaP from North Carolina and Louisiana were analyzed. Dietary carotenoid intake was assessed using a detailed-food frequency questionnaire (FFQ), and abdominal adipose tissue samples were analyzed for carotenoid concentrations using high-performance liquid chromatography. Multivariable logistic regression was used in race-stratified analyses to calculate odds ratios (ORs) and 95% confidence intervals (95%CI) comparing high aggressive CaP with low/intermediate aggressive CaP. RESULTS Carotenoid intake differed significantly between AAs and EAs, which included higher intake of lycopene among EAs and higher β−cryptoxanthin intake among AAs. Comparing the highest and lowest tertiles, dietary lycopene was associated inversely with high aggressive CaP among EAs (OR = 0.55, 95%CI: 0.34–0.89, Ptrend = 0.02), while an inverse association was observed between dietary β−cryptoxanthin intake and high aggressive CaP among AAs (OR = 0.56, 95%CI: 0.36–0.87, Ptrend = 0.01). Adipose tissue α−carotene and lycopene (cis + trans) concentrations were higher among EAs than AAs, and marginally significant inverse linear trends were observed for adipose α−carotene (Ptrend = 0.07) and lycopene (Ptrend = 0.11), and CaP aggressiveness among EAs only. CONCLUSIONS These results suggest that diets high in lycopene and β−cryptoxanthin may protect against aggressive CaP among EAs and AAs, respectively. Differences in dietary behaviors may explain the observed racial differences in associations. Prostate © 2016 Wiley Periodicals, Inc.

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

The authors examined the effects of Hurricanes Katrina and Rita (HKR) on cognitive and psychosocial functioning in a lifespan sample of adults 6 to 14 months after the storms. Participants were recruited from the Louisiana Healthy Aging Study (LHAS). Most were assessed during the immediate impact period and retested for this study. Analyses of pre-and post-disaster cognitive data confirmed that storm-related decrements in working memory for middle-aged and older adults observed in the immediate impact period had returned to pre-hurricane levels in the post-disaster recovery period. Middle-aged adults reported more storm-related stressors and greater levels of stress than the two older groups at both waves of testing. These results are consistent with a burden perspective on post-disaster psychological reactions.

Background: This study evaluated obesity and prostate cancer aggressiveness relationship in a population-based incident prostate cancer study. Methods: The North Carolina–Louisiana Prostate Cancer Project includes medical records data for classification of prostate cancer aggressiveness at diagnosis by using clinical criteria for 1,049 African American (AA) and 1,083 Caucasian American (CA) participants. An association between prostate cancer aggressiveness and obesity, measured using body mass indices (BMI) and waist-to-hip ratio (WHR), was assessed using ORs and 95% CIs adjusted for confounders. Results: A significantly positive association was found between prostate cancer aggressiveness and obesity. The ORs for high aggressive prostate cancer among prediagnosis obese and severely obese were 1.48 (95% CI = 1.02–2.16) and 1.98 (95% CI = 1.31–2.97), respectively, compared with normal weight research subjects. Race-stratified results suggested the association is stronger among CAs. Interaction model showed that normal weight AAs had more aggressive prostate cancer than normal weight CAs (OR = 2.69, 95% CI = 1.36–5.30); severe obesity was associated with aggressive disease in AAs (OR = 3.90, 95% CI = 1.97–7.75). WHR > 0.98 among all research subjects adjusted for race was significantly associated with high aggressive prostate cancer (OR = 1.42, 95% CI = 1.00–2.00) when compared with WHR < 0.90. The stratified result is less clear among AAs. Conclusions: This study shows a positive association between obesity and aggressive prostate cancer. AAs have more aggressive prostate cancer in general than CAs even at normal weight. Therefore, the association between obesity and aggressiveness is not as evident in AAs as in CAs. Impact: This study provides a unique opportunity to examine impact of race on obesity and high aggressive prostate cancer relationship. Cancer Epidemiol Biomarkers Prev; 20(5); 844–53. ©2011 AACR.

Metabolomics platforms allow for the measurement of hundreds to thousands of unique small chemical entities, as well as offer extensive coverage of metabolic markers related to obesity, diet, smoking, and other exposures of high interest to health scientists. Nevertheless, its potential use as a tool in population-based study design has not been fully explored. As the field of metabolomics continues to mature, and in part, accelerate through the National Institutes of Health (NIH) investment of ≤65 million in the Common Fund’s Metabolomics Program (https://common fund.nih.gov/metabolomics/index), it is time to consider those challenges most pertinent to epidemiologic studies.

Global hypomethylation in peripheral blood leukocyte DNA, measured by the reduction of genome-wide methylated cytosine (5-mC) or the long interspersed nuclear element-1 (LINE-1) level, has been associated with an increased risk of colorectal cancer, mainly in retrospective studies. Little is known as to how these global methylation markers relate in individuals and their associations with colorectal cancer risk in a prospective study setting. We studied leukocyte 5-mC and LINE-1 methylation levels in prospectively collected blood specimens from 404 cases and 528 controls who were free of colorectal cancer at blood collection from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Leukocyte 5-mC level was determined by an HPLC/Tandem Mass Spectrometry method and expressed as the relative amount of methyl- to total cytosine residues (%5-mC). LINE-1 methylation level was measured by McrBC digestion followed by real-time PCR of the undigested/unmethylated LINE1 promoter sequences. In our analysis, we excluded cases diagnosed within one year of blood draw to minimize the potential for reverse causation from prevalent disease. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for tertiles of methylation using multivariable logistic regression, adjusting for age, sex, and other potential confounders. We observed a significant association between low LINE-1 methylation and colorectal cancer risk (1st vs. 3rd tertile: OR=1.63, 95% CI=1.10-2.41; P trend=0.01) and a near-significant association with low %5-mC methylation (OR=1.37, 95% CI=0.92-2.03; P trend=0.15). The two markers were not correlated (Spearman's r=0.01). Comparing subjects with low methylation levels (1st tertiles) at both markers with those having the highest methylation level (3rd tertile) at either marker, we observed a stronger significant association (OR=2.49, 95% CI=1.62-3.81; P trend=0.0001). Interestingly, we also found that the association between natural folate intake and colorectal cancer risk was modified by %5-mC or two markers combined (P interaction= 0.0003 and 0.02, respectively). Among individuals with the highest methylation level at either marker, high natural folate intake (3rd tertile) was associated with a reduced risk of colorectal cancer compared to low (1st tertile) folate intake (OR=0.49, 95% CI=0.25-0.96); no association was observed among individuals with lower levels of methylation. No significant risk modification was found for other suspected risk factors, such as smoking, obesity, and aspirin/ibuprofen use. This prospective investigation showed that reduced LINE-1 methylation in leukocyte DNA, especially in conjunction with reduced 5-mC methylation, was associated with increased colorectal cancer risk. Folate may protect against colorectal carcinogenesis through mechanisms involving adequate DNA methylation in the genome. Citation Format: Wen-Yi Huang, Mark P. Purdue, L. Joseph Su, Hormuzd A. Katki, Lee E. Moore, Srinivasan Yegnasubramanian, Sonja I. Berndt. Prospective study of genomic 5-methylcytosine and LINE-1 methylation levels of leukocyte DNA and colorectal cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3231.

To investigate potential links between environmental exposure to petrochemical plant emissions and lung cancer, a population-based case-control study (LMRICS) was conducted in eleven Louisiana parishes bordering the Mississippi River. Cases and age, gender, and race-matched controls were interviewed regarding potential risk factors. Residential history was geocoded to provide indices of long-term proximity to industrial sites. Cases were more likely to have lived near a petrochemical site. Models adjusted for other risk factors, however, showed small or no association with lung cancer (odds ratio for residence within a half-mile of a site , 95% confidence interval 0.58–2.08). While associations were strongest for exposures exceeding 15 years, none approached statistical significance and there was no clear dose-response across exposure duration, distance categories, or when sites were grouped according to carcinogenicity rating of chemical releases. Residential proximity to petrochemical plants along the lower Mississippi thus showed no significant association with lung cancer.

Prostate cancer (PCa) is one of the most common cancers in the world. Inflammation has been described as a risk factor for PCa and depends on the production of cytokines in response to tissue damage or the presence of stimuli that induces cellular stress. Interindividual variation in cytokine production is partially controlled by single-nucleotide polymorphisms (SNPs) that have been associated with differential production of cytokines. We have recently showed that SNP-SNP interactions of cytokine genes are associated with PCa risk. However, little is known about the association of cytokine SNPs and PCa aggressiveness. In this study, we evaluated the association of 15 SNPs in five cytokine genes and aggressiveness of PCa in African- and Caucasian-American individuals. Caucasian Americans with the genotypes IL10-1082GG or IL1B+3954TT had 2.31-fold [95% confidence interval (CI) = 1.13-4.72] and 3.11 (95% CI = 1.20-8.06)-fold risk, respectively, of developing aggressive PCa, as compared with individuals without those genotypes. We did not find any associations in the African-American group. Using Multivariate Adaptive Regression Splines modeling for exploratory SNP-SNP interactions, our results showed that more aggressive PCa in Caucasians Americans is associated with the CT genotype at IL8-47 [odds ratios (OR) = 3.50; 95% CI = 1.13-10.88] or combined genotypes of IL1B-511CC and IL10-1082GG (OR = 3.38; 95% CI = 1.70-6.71). Unfortunately, the same analysis could not be performed in the African-Americans due to limited number of individuals. With limited sample size, the results from this study suggest that SNPs in cytokine genes may be associated with PCa aggressiveness. More extensive studies are warranted to validate our findings.

Prostate cancer is the most common non-cutaneous cancer and the second leading cause of cancer-related mortality among men in the USA. Growing evidence suggests that oxidative stress is involved in the development and progression of prostate cancer. In this study, the association between antioxidants from diet and supplements and biomarkers of oxidative stress in blood (n 278), urine (n 298) and prostate tissue (n 55) were determined among men from the North Carolina-Louisiana Prostate Cancer Project. The association between antioxidant intake and oxidative stress biomarkers in blood and urine was determined using linear regression, adjusting for age, race, prostate cancer aggressiveness and smoking status. Greater antioxidant intake was found to be associated with lower urinary 8-isoprostane concentrations, with a 10 % increase in antioxidant intake corresponding to an unadjusted 1·1 % decrease in urinary 8-isoprostane levels (95 % CI −1·7, −0·3 %; P valueP value=0·16). In benign prostate tissue, thioredoxin 1 was inversely associated with antioxidant intake (P=0·02). No significant associations were found for other blood or urinary biomarkers or for malignant prostate tissue. These results indicate that antioxidant intake may be associated with less oxidative stress among men diagnosed with prostate cancer.

Breast cancer is the most common non-skin cancer in women in the United States. The incidence rate of breast cancer among migrant women from Asian countries, where the breast cancer incidence is low, could achieve the rate of the United States within two generations. Maternal exposures to various environmental factors during pregnancy have been hypothesized to be associated with offsprings’ breast cancer risk. These exposures may change various carcinogenesis-related hormone levels and alter the epigenome among offsprings, which increase their breast cancer risk in later life. The effect of maternal pregnancy exposures on offsprings’ breast cancer via epigenetic modifications could be carried out through multiple generations of offspring. In this chapter, we aim to summarize findings from both experimental and epidemiological studies investigating associations between maternal pregnancy exposures and offspring’s breast cancer risk.

Obesity is a major health problem today that grows into a global epidemic. Obesity has been associated with increased risk of many non-communicable diseases, such as type-2 diabetes mellitus, hypertension, cardiovascular diseases and cancer. There are multiple factors that cause obesity. Accelerated lifestyle, fast food, unhealthy eating habits and sedentary lifestyle have been considered as the major risk factors of overweight and obesity development. It has been suggested that genetic factors may play an important part of the onset of obesity. However, the observed rapid rise of obesity worldwide has occurred too rapidly to be solely explained by fixed genomic variation in combination with adult lifestyle factors. Epigenetic modifications can be programmed in the intrauterine environment and can be modulated by environmental influences including diet besides genetic influences. It has been widely accepted that genes together with adult lifestyle factors determine the risk of developing non-communicable diseases. Animal study models have demonstrated that epigenetic alternations early in life lead to obesity later in adult life. Natural human experiment, such as Dutch famine study, also suggested that peri-conceptional and peri-natal nutrient deficiency resulted in overweight or obesity later in life. The results from epidemiologic studies are less consistent. This chapter reviewed the evidence from animal studies, ecologic evaluation, to epidemiologic studies to assess whether there is a causal relationship between epigenetics modification from diet and environmental exposure and obesity. Challenges and opportunities to improve the future study design in human are explored.

Objective To examine the relationship between reported salad consumption and serum nutrient levels as well as dietary adequacy, as defined by nutrient intakes, in relation to the National Academy of Science Food and Nutrition Board Guidelines, in pre- and postmenopausal women and in men of comparable ages. Design Analyses of 24-hour recalls were conducted to determine dietary intake using the Third National Health and Nutrition Examination Survey data. Salad consumption was assessed based on intakes of salad, raw vegetables, and salad dressing. Subjects Nine thousand four hundred-six women and 8,282 men aged 18 to 45 years and older than 55 years were examined between 1988 and 1994. Statistical Analyses Regressions were used to model associations between salad and raw vegetable consumption and selected serum nutrient outcomes. Usual nutrient intake distributions were estimated using the Iowa State University method for adjustment of the distribution. The Estimated Average Requirement method was used to determine the proportion of subjects with inadequate intake for each nutrient. Results The consumption of salads, raw vegetables, and salad dressing was positively associated with above-median serum micronutrient levels of folic acid, vitamins C and E, lycopene, and α- and β-carotene. Each serving of salad consumed was associated with a 165% higher likelihood to meet the recommended Dietary Allowance for vitamin C in women and 119% greater likelihood in men. Conclusions Salad consumers tended to have more favorable intakes of vitamins C and E, folic acid, and carotenoids, after adjustment for other differences. The significant and consistently higher serum values of these vitamins among salad consumers suggest that they are being well absorbed from salad. Salad, salad dressing, and raw vegetable consumption can be an effective strategy for enhancing nutritional adequacy and increasing vegetable consumption in the population at large.

BACKGROUND The authors examined subsite-specific and histology-specific esophageal and gastric carcinoma incidence patterns among the Asians/Pacific Islander (API) population in the United States and compared them with those among whites and blacks. METHODS Data on newly diagnosed esophageal and gastric carcinomas during 1996–2000 were obtained from 24 population-based central cancer registries, representing approximately 80% of the API population in the United States. Age-adjusted rates, using the 2000 United States standard population, and age-specific rates were computed by anatomic subsite, histology, race, and gender. The difference in the age-adjusted rates between APIs and other races were examined using the two-tailed z statistic. RESULTS Greater than 75% of esophageal carcinomas among APIs, both males and females, were squamous cell carcinoma. Adenocarcinoma accounted for < 20% of all esophageal carcinomas. This pattern was similar to that among blacks but was completely opposite to that among whites. The rate of esophageal squamous cell carcinoma was 81% higher among API males compared with white males, but it was 64% less compared with black males. The rates of esophageal adenocarcinoma were significantly lower among APIs than among both whites and blacks both males and females. The majority of gastric carcinomas among APIs were noncardia adenocarcinoma, whereas cardia adenocarcinoma accounted for only 11% of gastric carcinomas among API males and 6% of gastric carcinomas among API females. The age-adjusted incidence rate of cardia adenocarcinoma was 23% lower among API males compared with white males, but it was 26% higher compared with black males. In contrast, the rates of noncardia adenocarcinoma among APIs were approximately 3.7 times the rate among whites for both males and females and 33% higher than the rate among blacks. CONCLUSIONS Subsite-specific and histology-specific incidence patterns of esophagogastric carcinoma among APIs differ from those among whites and blacks. The reasons for significantly higher rates of noncardia adenocarcinoma among APIs compared with whites and blacks need further investigation. Cancer 2006. © 2005 American Cancer Society.

BACKGROUND The North Carolina–Louisiana Prostate Cancer Project (PCaP) is a multidisciplinary study of social, individual, and tumor-level causes of racial differences in prostate cancer aggressiveness. METHODS A population-based sample of incident prostate cancer cases from North Carolina and Louisiana will include 1,000 African Americans and 1,000 Caucasian Americans. Study nurses administer structured questionnaires and collect blood, adipose tissue, urine, and toenail samples during an in-home visit. Clinical data are abstracted from medical records, diagnostic biopsies are reviewed and assayed, and tissue microarrays are constructed from prostatectomy samples. Prostate cancer aggressiveness is classified based on PSA, clinical stage, and Gleason grade. RESULTS Preliminary data demonstrate between- and within-group differences in patient characteristics, screening, and treatment by race and state. Participation exceeds 70% in all groups. CONCLUSIONS Preliminary data support the feasibility of this comprehensive study to help determine the focus of public health efforts to reduce racial disparities in prostate cancer mortality. Prostate © 2006 Wiley-Liss, Inc.

Objective:This study examines the relationship between tea consumption and colon cancer risk in the US population.Design:Data from the NHANES I Epidemiologic Follow-up study (NHEFS) were used to examine the hypothesis. Cox proportional hazard models were used to examine the hypothesis of a protective effect of frequent tea consumption on colon cancer occurrence.Setting:Due to differences in the precision of the exposure data, we analysed two cohort periods based on the NHEFS. Cohort I was based on the survey conducted at the NHEFS baseline and Cohort II began at the first follow-up.Subjects:After excluding non-incidence cases and cases lost to follow-ups, there were 2359 tea users and 6498 non-tea users at baseline and 7656 tea users and 4514 non-tea users at the first follow-up.Results:After adjusting for confounders, the relative risks of colon cancer are 0.57 (95% confidence interval (CI) 0.42, 0.78) and 0.59 (95% CI = 0.35, 1.00) for subjects who consumed ≤1.5 cups and ≥1.5 cups per day, respectively, compared with non-tea users in Cohort II. Although more women consumed tea and the mean intake was higher, the preventive effect of tea consumption on colon cancer was found predominantly in men. The relative risks of colon cancer are 0.41 (95% CI = 0.25, 0.66) for men who consumed ≤1.5 cups day-1 and 0.30 (95% CI = 0.09, 0.98) for >1.5 cups day-1 of tea consumption (P-value for trend Conclusions:This study suggests an inverse association between colon cancer risk and habitual tea consumption.