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Genetic variants related to colorectal adenoma may help identify those who are at highest risk of colorectal cancer development or illuminate potential chemopreventive strategies. The purpose of this genome-wide association study was to identify genetic variants that are associated with risk of developing a metachronous colorectal adenoma among 1,215 study participants of European descent from the Selenium Trial. Associations of variants were assessed with logistic regression analyses and validated in an independent case-control study population of 1,491 participants from the Colorectal Cancer Study of Austria (CORSA). No statistically significant genome-wide associations between any variant and metachronous adenoma were identified after correction for multiple comparisons. However, an intron variant of

PDF file - 636K, Representative images of ALDH1 staining and enumeration by Aperio Genie with color.

PDF file - 20K, Supplemental Figure showing ALDH1 intra-class correlation.

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Perspective from Difluoromethylornithine Plus Sulindac for the Prevention of Sporadic Colorectal Adenomas: A Randomized Placebo-Controlled, Double-Blind Trial

Background: Adenomatous polyps are the most common precursor to colorectal cancer, the second leading cause of cancer-related death in the United States. We sought to learn more about early events of carcinogenesis by investigating shifts in the gut microbiota of patients with adenomas.Methods: We analyzed 16S rRNA gene sequences from the fecal microbiota of patients with adenomas (n = 233) and without (n = 547).Results: Multiple taxa were significantly more abundant in patients with adenomas, including Bilophila, Desulfovibrio, proinflammatory bacteria in the genus Mogibacterium, and multiple Bacteroidetes species. Patients without adenomas had greater abundances of Veillonella, Firmicutes (Order Clostridia), and Actinobacteria (family Bifidobacteriales). Our findings were consistent with previously reported shifts in the gut microbiota of colorectal cancer patients. Importantly, the altered adenoma profile is predicted to increase primary and secondary bile acid production, as well as starch, sucrose, lipid, and phenylpropanoid metabolism.Conclusions: These data hint that increased sugar, protein, and lipid metabolism along with increased bile acid production could promote a colonic environment that supports the growth of bile-tolerant microbes such as Bilophilia and Desulfovibrio. In turn, these microbes may produce genotoxic or inflammatory metabolites such as H2S and secondary bile acids, which could play a role in catalyzing adenoma development and eventually colorectal cancer.Impact: This study suggests a plausible biological mechanism to explain the links between shifts in the microbiota and colorectal cancer. This represents a first step toward resolving the complex interactions that shape the adenoma–carcinoma sequence of colorectal cancer and may facilitate personalized therapeutics focused on the microbiota. Cancer Epidemiol Biomarkers Prev; 26(1); 85–94. ©2016 AACR.

Supplementary Table 1. MiRKAT association P values for various adenoma characteristics in individuals with adenomas

Supplementary Figure 2. Heat map of significantly predictive taxa. Hierarchical clustering is based on the Euclidean distance of log proportion, complete linkage. The left cluster is enriched in adenoma samples (P=0.1, Fisher's exact test).

BACKGROUND: Selenium (Se) is a trace element that has been linked to many health conditions. Genome-wide association studies (GWAS) have identified variants for blood and toenail Se levels, but no GWAS has been conducted to date on responses to Se supplementation. OBJECTIVES: A GWAS was performed to identify the single nucleotide polymorphisms (SNPs) associated with changes in Se concentrations after 1 year of supplementation. A GWAS of basal plasma Se concentrations at study entry was conducted to evaluate whether SNPs for Se responses overlap with SNPs for basal Se levels. METHODS: A total of 428 participants aged 40–80 years of European descent from the Selenium and Celecoxib Trial (Sel/Cel Trial) who received daily supplementation with 200 µg of selenized yeast were included for the GWAS of responses to supplementation. Plasma Se concentrations were measured from blood samples collected at the time of recruitment and after 1 year of supplementation. Linear regression analyses were performed to assess the relationship between each SNP and changes in Se concentrations. We further examined whether the identified SNPs overlapped with those related to basal Se concentrations. RESULTS: No SNP was significantly associated with changes in Se concentration at a genome-wide significance level. However, rs56856693, located upstream of the NEK6, was nominally associated with changes in Se concentrations after supplementation (P = 4.41 × 10(−7)), as were 2 additional SNPs, rs11960388 and rs6887869, located in the dimethylglycine dehydrogenase (DMGDH)/betaine-homocysteine S-methyltransferase (BHMT) region (P = 0.01). Alleles of 2 SNPs in the DMGDH/BHMT region associated with greater increases in Se concentrations after supplementation were also strongly associated with higher basal Se concentrations (P = 8.67 × 10(−8)). CONCLUSIONS: This first GWAS of responses to Se supplementation in participants of European descent from the Sel/Cel Trial suggests that SNPs in the NEK6 and DMGDH/BHMT regions influence responses to supplementation.

BACKGROUND The Partnership for HIV-Free Survival (PHFS) in Uganda used a quality improvement (QI) approach to integrate the prevention of mother-to-child transmission (MTCT) of HIV, maternal and child health, and nutrition services, with the goal of increasing the retention of mother-baby pairs in care and decreasing vertical transmission of HIV. METHODS This evaluation of PHFS used a retrospective longitudinal design to assess the program's association with 4 outcomes. Data were extracted from patient records from 2011 (before the program) to 2018 (after the program) at 18 demonstration, 18 scale-up, and 24 comparison facilities. Difference-in-differences analyses were conducted with significance set at P 0.15 or a significant continued improvement after PHFS. RESULTS PHFS was associated with an increase in exclusive breastfeeding (EBF) (P = 0.08), 12-month retention in care (P < 0.001), and completeness of child 18-month HIV test results (P = 0.13) at demonstration facilities during program implementation. MTCT at 18 months decreased, but did not differ between groups. Increases in EBF (P = 0.67) and retention in care (P = 0.16) were sustained, and data completeness (P = 0.10) continued to increase at demonstration facilities after the program. PHFS was associated with an increase in EBF (P < 0.001) at scale-up facilities, but there was no difference between groups for retention in care, MTCT, or data completeness. Gains in EBF were lost (P = 0.08) and retention in care declined (P < 0.001) at scale-up facilities after the program. CONCLUSION PHFS' quality improvement approach increased EBF, retention in care, and data completeness in demonstration facilities during the program and these benefits were sustained.

Oxylipins derived from arachidonic acid (ARA) have been implicated in the development of colorectal adenomas and colorectal cancer. The primary purpose of this work was to determine the relationship between plasma levels of oxylipins and colorectal adenoma characteristics at study entry, as well as with the development of a new adenoma during follow-up within a Phase III adenoma prevention clinical trial with selenium (Sel). Secondarily, we sought to determine whether the selenium intervention influenced plasma oxylipin levels. Four oxylipins were quantified in stored plasma samples from a subset of Sel study subjects (n = 256) at baseline and at 12-months. There were significantly lower odds of an advanced adenoma at baseline with higher prostaglandin E2 (PGE2), with an OR (95% CI) of 0.55 (0.33–0.92), and with 5-hydroxyeicosatetraenoic acid (5-HETE) ((0.53 (0.33–0.94)), and of a large adenoma with higher PGE2 ((0.52 (0.31–0.87)). In contrast, no associations were observed between any oxylipin and the development of a new adenoma during follow-up. Selenium supplementation was associated with a significantly smaller increase in 5-HETE after 12 months compared to the placebo, though no other results were statistically significant. The ARA-derived oxylipins may have a role in the progression of non-advanced adenoma to advanced, but not with the development of a new adenoma.

Background American Indians (AI) experience major colorectal cancer (CRC) screening disparities with commensurate inequity in CRC mortality and other outcomes. The purpose of this report is to describe the methods and early results of adapting a previously successful intervention for the AI community. Methods The educational content and delivery strategy of the parent intervention were adapted for AIs guided by an adaptation framework and cultural consultations with the community and clinicians. As part of the environmental scanning, we identified the need to substantively revise our data entry, collection, and tracking system and develop a REDCap database for this purpose. In this study, we staggered the implementation of the intervention in each facility to inform the process from one clinic to the next, and assess both the clinical outcomes of the tailored intervention and the implementation processes across two clinic settings, Facilities A and B. Results The REDCap database is an indispensable asset, and without it we would not have been able to obtain reliable aggregate screening data while improvements to facility electronic health records are in progress. Approximately 8% (n = 678) of screening-eligible patients have been exposed to the navigator intervention. Of those exposed to the navigator intervention, 37% completed screening. Conclusions With the small numbers of patients exposed so far to the intervention, it would be premature to draw any broad conclusions yet about intervention effects. However, early screening completion rates are substantial advances on existing rates, and we have demonstrated that a tailored navigator intervention for facilitating CRC screening was readily adapted with provider and community input for application to AIs. A REDCap database for tracking of CRC screening by navigators using tablets or laptops on- or offline is easy to use and allows for generation of aggregate, anonymized screening data. Trial registration. There was no health intervention meeting the criteria of a clinical trial. The University of Arizona Institutional Review Board granted exemption from obtaining informed consent from patients undergoing CRC screening after administration of the tailored navigation intervention as usual care.

Rationale: Patients with chronic lung disease have an increased risk for severe coronavirus disease-19 (COVID-19) and poor outcomes. Objectives: To identify molecular characteristics of diseased lung epithelial and immune cells that may account for worse COVID-19 outcomes in patients with chronic lung diseases. Methods: We analyzed the transcriptomes of 605,904 single cells isolated from healthy (79 samples) and diseased human lungs (31 chronic obstructive pulmonary disease (COPD), 82 idiopathic pulmonary fibrosis (IPF) and 18 non-IPF interstitial lung disease samples). Measurements and Main Results: Cellular distribution and relative expression of SARS-CoV-2 entry factors (ACE2, TMPRSS2) was similar in disease and control lungs. Epithelial cells isolated from diseased lungs expressed higher levels of genes linked directly to efficiency of viral replication and the innate immune response. Unique ACE2-correlated gene sets were identified for each diagnosis group in the type II alveolar cells. Diseased lungs have a significant increase in the proportion of CD4, CD8 and NK cells compared to control lungs. Components of the interferon pathway, the IL6 cytokine pathway and the major histocompatibility complex (MHC) class II genes are upregulated in several diseased immune cell types. These differences in inflammatory gene expression programs highlight how chronic lung disease alters the inflammatory microenvironment encountered upon viral exposure to the peripheral lung. Conclusions: Chronic lung disease is accompanied by changes in cell-type-specific gene expression programs that prime the lung epithelium for and influence innate and adaptive immune responses to SARS-CoV-2 infection.

To evaluate whether contraceptive insurance coverage for women who present for an abortion is associated with obtaining long-acting reversible contraception or depot medroxyprogesterone acetate (DMPA) on the day the abortion is completed.We conducted a prospective cohort study of women presenting for medical or surgical abortion at a single health center in North Carolina. Eligible women were 18 years or older and fluent in English or Spanish. Data were from participant questionnaires, medical charts, and financial records. Our main exposure was whether the woman had insurance coverage for contraception at clinic intake. Our primary outcome was receiving DMPA, an intrauterine device, or a contraceptive subdermal implant on the same day of their surgical abortion or at the visit that determined their medication abortion was complete. We used univariable, bivariable, and multivariable analysis to report our findings.Five hundred seventy-five women enrolled in our cohort between September 2015 and April 2016. One hundred twenty-eight (22%) had insurance coverage and 447 (78%) did not. In the group with insurance coverage for contraception, 38% (49/128) received a long-acting reversible contraception method or DMPA compared with 7% (33/447) in the group without insurance coverage for contraception. After adjusting for confounding, women with contraceptive coverage were more than five times as likely to receive immediate postabortion contraception with one of these methods compared with women without coverage (relative risk 5.6, 95% confidence interval 3.8-8.3).Women with contraceptive insurance coverage on the day of their abortion were more likely to leave the abortion clinic with an intrauterine device or implant in place or receive DMPA injection compared with women without coverage.

Background Colorectal cancer screening remains suboptimal among poor and underserved people. Purpose We tested the effectiveness of a community-to-clinic navigator intervention to guide multicultural, underinsured individuals into primary care clinics to complete colorectal cancer screening. Methods This two-phase behavioral intervention study was conducted in Phoenix, Arizona (2012–2018). Community sites were randomized to group education or group education plus tailored navigation to increase attendance at primary care clinics (Phase I). Individuals who completed a clinic appointment received the tailored navigation in person or via phone (Phase II). Results In Phase I (N = 345), 37.9% of the intervention group scheduled a clinic appointment versus 19.4% of the comparison group. In Phase II, 26.5% of the original intervention group were screened versus only 10.4% of the original comparison group. Those in the intervention group were 3.84 times more likely to be screened than were those in the comparison group (odds ratio = 3.84; 95% confidence interval = 1.81–6.92). Conclusions Translation of an efficacious tailored navigation intervention for colorectal cancer screening to a community-to-clinic context is associated with significantly increased rates of colorectal cancer screening. Navigation assistance to address barriers to screening may serve as the most important component of any educational program to increase individual adherence to colorectal cancer screening.

Background To date, there is little information on the sustainability of family planning (FP) service quality after completion of a donor-funded program. This paper examines the sustainability of the Nigerian Urban Reproductive Health Initiative (NURHI) program on quality of FP services in two cities: Ilorin, where the program ended in March 2015 and Kaduna where the program continued. Methods Data come from three time periods: 2011, before program implementation; 2014, near Phase 1 completion; and 2017, two-years post Phase 1. In 2011, we undertook a facility audit and provider surveys in all public sector facilities in each city as well as all private facilities mentioned as the source for FP or maternal, newborn, and child health services in a 2010 women’s household survey. In 2014 and 2017, we returned to the same facilities to undertake the facility audit and provider surveys. Quality is measured from principal component analyses of 30 items from the facility audit and provider surveys. Service use outcomes are measured as the ratio of FP clients (total and new) to the number of reproductive health staff members. Multivariate random effect models are estimated to examine changes in the outcomes over time, between NURHI and non-NURHI facilities and by city. Results We demonstrate that NURHI facilities had better quality and higher service use than non-NURHI facilities. Further, while quality of services was higher in Ilorin in 2011, by 2014 and three years later (2017), the quality was better in Kaduna where the program continued. In addition, while no difference was found in service utilization between Ilorin and Kaduna in 2014, by 2017, Kaduna had significantly more new FP users than Ilorin. Conclusions In Ilorin, quality of services did not continue its strong upward trend after the program ended. Programs need to consider long-term strategies that support continuation of program components post program implementation. This may include ensuring continued training of providers and addressing equipment and commodity stock-outs through system changes rather than specific facility-level changes. The findings from this study can be used to inform future programs seeking to improve quality of FP services in a sustainable manner. Electronic supplementary material The online version of this article (10.1186/s12913-019-4388-3) contains supplementary material, which is available to authorized users.

Few studies have examined the sustainability of family planning program outcomes in the post-program period. This article presents the results of a natural experiment where the Nigerian Urban Reproductive Health Initiative Phase I programming ended in early 2015 and Phase II activities continued in a subset of cities. Using data collected in 2015 and 2017, we compare contraceptive ideation and modern family planning use in two cities: Ilorin where program activities concluded in 2015 and Kaduna where program activities continued. The results demonstrate that exposure to program activities decreased in Ilorin but for those individuals reporting continuing exposure, the effect size of exposure on modern family planning use remained the same and was not significantly different from Kaduna. Modern family planning use continued to increase in both cites but at a lower rate than during Phase I. The results are useful for designing family planning programs that sustain beyond the life of the program.

It has been previously reported that ursodeoxycholic acid (UDCA), a therapeutic bile acid, reduced risk for advanced colorectal adenoma in men but not women. Interactions between the gut microbiome and fecal bile acid composition as a factor in colorectal cancer neoplasia have been postulated but evidence is limited to small cohorts and animal studies. Using banked stool samples collected as part of a phase III randomized clinical trial of UDCA for the prevention of colorectal adenomatous polyps, we compared change in the microbiome composition after a 3‐year intervention in a subset of participants randomized to oral UDCA at 8‐10 mg/kg of body weight per day (n = 198) or placebo (n = 203). Study participants randomized to UDCA experienced compositional changes in their microbiome that were statistically more similar to other individuals in the UDCA arm than to those in the placebo arm. This reflected a UDCA‐associated shift in microbial community composition (P < 0.001), independent of sex, with no evidence of a UDCA effect on microbial richness (P > 0.05). These UDCA‐associated shifts in microbial community distance metrics from baseline to end‐of‐study were not associated with risk of any or advanced adenoma (all P > 0.05) in men or women. Separate analyses of microbial networks revealed an overrepresentation of Faecalibacterium prausnitzii in the post‐UDCA arm and an inverse relationship between F prausnitzii and Ruminococcus gnavus. In men who received UDCA, the overrepresentation of F prausnitzii and underrepresentation of R gnavus were more prominent in those with no adenoma recurrence at follow‐up compared to men with recurrence. This relationship was not observed in women. Daily UDCA use modestly influences the relative abundance of microbial species in stool and affects the microbial network composition with suggestive evidence for sex‐specific effects of UDCA on stool microbial community composition as a modifier of colorectal adenoma risk. ISSN:2045-7634

Colorectal cancer and adenoma adjacent to cancer exhibit distinct microRNA (miRNA) alterations in an apparent mucosa-to-adenocarcinoma sequence. The pattern of microRNAs in screen-detected polyps in relation to histologic features and cancer risk has not been investigated. miRNA expression analysis was performed on normal mucosa (NM), hyperplastic polyps (HP), tubular adenomas (TA), tubulovillous adenomas or high-grade dysplasia (TVHG), and serrated polyps [sessile serrated adenoma/polyps (SSA/P) and traditional serrated adenomas (TSA)] in biopsy specimens from 109 patients undergoing screening/surveillance colonoscopy. Generalized linear models were used to identify differentially expressed miRNAs by histologic type and logistic regression to identify miRNA predictors of histopathology. False discovery rate (FDR) was used to control for multiple comparisons. We identified 99 miRNAs differing in at least one of five histopathologic groups (FDR ≤0.05). In a comparison of HPNM versus TVHG, the top most upregulated and downregulated miRNAs in HPNM included miR-145, -143, -107, -194, and -26a (upregulated), and miR-663, -1268, -320b, -1275, and -320b (downregulated; FDR P < 0.05). miR-145 and -619 showed high accuracy to discriminate low- from high-risk polyps without serrated histology (TVHG vs. HPNM + TA; CI, 95.6%), whereas miR-124, -143, and -30a showed high accuracy of separating high-risk polyps (TVHG + TSA) from low-risk polyps (HPNM + TA + SSA/P; CI, 96.0%). For TSAs, miR-125b and -199a were uniquely downregulated relative to HPNMs, and miR-335, -222, and -214 discriminated between non-serrated and serrated histology. Our data support the presence of colorectal cancer–associated miRNA alterations in screen-detected adenomas that may be useful for risk stratification for surveillance interval planning. Cancer Prev Res; 9(12); 942–9. ©2016 AACR.

The Mayer Hashi program resulted in a modest increase in use of long-acting reversible contraceptives and permanent methods in Bangladesh, but less of an increase than in comparison nonprogram districts, which appears to have been the result of weaknesses in the health system environment in the program districts. Addressing system issues to support providers beyond training might have led to better results., Background: Bangladesh has achieved a low total fertility rate of 2.3. Two-thirds of currently married women of reproductive age (CMWRA) want to limit fertility, and many women achieve their desired fertility before age 30. The incidence of unintended pregnancy and pregnancy termination is high, however. Long-acting reversible contraceptives (LARCs), consisting of the intrauterine device and implant, and permanent methods (PM), including female sterilization and vasectomy, offer several advantages in this situation, but only 8% of CMWRA or 13% of method users use these methods. Program: The Mayer Hashi (MH) program (2009–2013) aimed to improve access to and the quality of LARC/PM services in 21 of the 64 districts in Bangladesh. It was grounded in the SEED (supply–enabling environment–demand) Programming Model. Supply improvements addressed provider knowledge and skills, system strengthening, and logistics. Creating an enabling environment involved holding workshops with local and community leaders, including religious leaders, to encourage them to help promote demand for LARCs and PMs and overcome cultural barriers. Demand promotion encompassed training of providers in counseling, distribution of behavior change communication materials in the community and in facilities, and community mobilization. Methods: We selected 6 MH program districts and 3 nonprogram districts to evaluate the program. We used a before–after and intervention–comparison design to measure the changes in key contraceptive behavior outcomes, and we used a difference-in-differences (DID) specification with comparison to the nonprogram districts to capture the impact of the program. In addition to the outcome evaluation, we considered intermediate indicators that measured the processes through which the interventions were expected to affect the use of LARCs and PMs. Results: The use of LARCs/PMs among CMWRA increased between 2010 and 2013 in both program (from 5.3% to 7.5%) and nonprogram (from 5.0% to 8.9%) districts, but the rate of change was higher in the nonprogram districts. Client–provider interaction and exposure to LARCs/PMs were lower in the program than nonprogram districts, and the MH program districts had higher vacancies of key providers than the nonprogram areas, both indications of a more difficult health system environment. Conclusion: The weaknesses in the health system in the MH districts apparently undermined the effectiveness of the program. More attention to system weaknesses, such as additional supportive supervision for providers, might have improved the outcome.

Although hydrophobic bile acids have been demonstrated to exhibit cytotoxic and carcinogenic effects in the colorectum, ursodeoxycholic acid (UDCA) has been investigated as a potential chemopreventive agent. Vitamin D has been shown to play a role in both bile acid metabolism and in the development of colorectal neoplasia. Using a cross-sectional design, we sought to determine whether baseline circulating concentrations of the vitamin D metabolites 25(OH)D and 1,25(OH)2D were associated with baseline fecal bile acid concentrations in a trial of UDCA for the prevention of colorectal adenoma recurrence. We also prospectively evaluated whether vitamin D metabolite concentrations modified the effect of UDCA on adenoma recurrence. After adjustment for age, sex, BMI, physical activity, and calcium intake, adequate concentrations of 25(OH)D (≥30 ng/mL) were statistically significantly associated with reduced odds for high levels of total [OR, 0.61; 95% confidence interval (CI), 0.38–0.97], and primary (OR, 0.61; 95% CI, 0.38–0.96) bile acids, as well as individually with chenodeoxycholic acid (OR, 0.39; 95% CI, 0.24–0.63) and cholic acid (OR, 0.56; 95% CI, 0.36–0.90). No significant associations were observed for 1,25(OH)2D and high versus low fecal bile acid concentrations. In addition, neither 25(OH)D nor 1,25(OH)2D modified the effect of UDCA on colorectal adenoma recurrence. In conclusion, this is the first study to demonstrate an inverse relationship between circulating levels of 25(OH)D and primary fecal bile acid concentrations. These results support prior data demonstrating that vitamin D plays a key role in bile acid metabolism, and suggest a potential mechanism of action for 25(OH)D in colorectal cancer prevention. Cancer Prev Res; 9(7); 589–97. ©2016 AACR.

Background The farnesoid X receptor (FXR) regulates bile acid (BA) metabolism and possesses tumor suppressor functions. FXR expression is reduced in colorectal tumors of subjects carrying inactivated adenomatous polyposis coli (APC). Identifying the mechanisms responsible for this reduction may offer new molecular targets for colon cancer prevention. Objective We investigated how APC inactivation influences the regulation of FXR expression in colonic mucosal cells. We hypothesized that APC inactivation would epigenetically repress nuclear receptor subfamily 1, group H, member 4 (FXR gene name) expression through increased CpG methylation. Methods Normal proximal colonic mucosa and normal-appearing adjacent colonic mucosa and colon tumors were collected from wild-type C57BL/6J and Apc-deficient (Apc(Min) (/+)) male mice, respectively. The expression of Fxr, ileal bile acid-binding protein (Ibabp), small heterodimer partner (Shp), and cyclooxygenase-2 (Cox-2) were determined by real-time polymerase chain reaction. In both normal and adjacent colonic mucosa and colon tumors, we measured CpG methylation of Fxr in bisulfonated genomic DNA. In vitro, we measured the impact of APC inactivation and deoxycholic acid (DCA) treatment on FXR expression in human colon cancer HCT-116 cells transfected with silencing RNA for APC and HT-29 cells carrying inactivated APC. Results In Apc(Min) (/+) mice, constitutive CpG methylation of the Fxrα3/4 promoter was linked to reduced (60-90%) baseline Fxr, Ibabp, and Shp and increased Cox-2 expression in apparently normal adjacent mucosa and colon tumors. Apc knockdown in HCT-116 cells increased cellular myelocytomatosis (c-MYC) and lowered (∼50%) FXR expression, which was further reduced (∼80%) by DCA. In human HCT-116 but not HT-29 colon cancer cells, DCA induced FXR expression and lowered CpG methylation of FXR. Conclusions We conclude that the loss of APC function favors the silencing of FXR expression through CpG hypermethylation in mouse colonic mucosa and human colon cells, leading to reduced expression of downstream targets (SHP, IBABP) involved in BA homeostasis while increasing the expression of factors (COX-2, c-MYC) that contribute to inflammation and colon cancer.

Despite the proven effectiveness of colorectal cancer (CRC) screening, American Indians (AIs) have some of the lowest CRC screening rates. Nearly two-thirds of US adults are current with US Preventive Services Task Force guidelines for CRC screening. In contrast, based on Indian Health Service (IHS) Government Performance and Results Act (GPRA) data, AI screening rates range from a low of 28% in the Phoenix Area, to 30% in the Albuquerque Area and a high of only 51% in the Oklahoma Area. The AI CRC Screening Consortium was formed by the National Cancer Institute-Designated Cancer Centers at the Universities of Arizona, New Mexico, and Oklahoma to address the major regional CRC screening disparities. The Consortium’s overall objective is to increase CRC screening delivery and uptake in AIs aged 50 to 75 years at average risk for CRC through the implementation of cost-effective multilevel, multicomponent evidence-based interventions (EBIs) across AI populations (on and off tribal lands) in the tri-state region. As part of the planning phase of the project (Year 1), we completed mixed-methods environmental scans (focus group and interviews, and readiness to change surveys) among tribal members and multisector healthcare providers practicing at Indian Health Service (IHS, I), Tribal (T), and Urban Indian (U) (I/T/U) healthcare facilities across the three states. In all, we conducted seven focus groups, 71 interviews, and three surveys at nine I/T/U healthcare facilities. We organized the focus group and interview data according to The Guide to Community Preventive Services (The Community Guide) recommendations for strategies to increase: community demand, community access, and provider delivery of CRC screening. We will provide quotes and summaries underscoring the EBIs and strategies recommended by the multisector healthcare action teams for implementation at their healthcare facilities. We will also describe the establishment of the Consortium and challenges experienced in conducting research with multiple tribal and federal entities and regulatory authorities. The use of community-academic participatory approaches has facilitated bidirectional and mutually beneficial knowledge integration, collaborative inter-dependent partnerships, equity in data ownership, and capacity enhancement. The scope of this project presents an opportunity to reduce CRC incidence and mortality affecting thousands of AIs. Our collaborative work will create opportunities for future research addressing the spectrum of CRC prevention, detection, and treatment in AI populations across the US. Citation Format: Shiraz I Mishra, Mark P Doescher, Jennifer Hatcher, Kevin English, Dorothy Rhoades, Peter Lance, Shane Pankratz, Jessica Blanchard, Nicholas Edwardson, Michelle Hopkins, Andrew Sussman, Zsolt Nagykaldi, Cheyenne Jim. Evidence-based strategies to enhance colorectal cancer screening in American Indian 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 C120.

ObjectiveWhile controversial, observational and randomized clinical trial data implicate the micronutrient selenium (Se) in the development of type 2 diabetes (T2D). The aim of this study was to test the hypothesis that Se supplementation adversely affects pancreatic β-cell function and insulin sensitivity.Research design and methodsIn a subset of 400 individuals participating in a randomized, placebo-controlled trial of Se at 200 µg/day for colorectal adenomatous polyps, fasting plasma glucose and insulin were measured before randomization and within 6 months of completing intervention. Change in the homeostasis model assessment-β cell function (HOMA2-%β) and insulin sensitivity (HOMA2-%S) were compared between arms. A subgroup of 175 (79 Se and 96 placebo) participants underwent a modified oral glucose tolerance test (mOGTT) at the end of intervention and change in glucose values was assessed.ResultsNo statistically significant differences were observed for changes in HOMA2-%β or HOMA2-%S between those who received Se compared with placebo. After a mean of 2.9 years on study, mean HOMA2-%β values were 3.1±24.0 and 3.1±29.8 for the Se and placebo groups, respectively (p=0.99). For HOMA2-%S, the values were −0.5±223.2 and 80.9±1530.9 for the Se and placebo groups, respectively (p=1.00). Stratification by sex or age did not reveal any statistically significant effects on insulin sensitivity by treatment group. For mOGTT, mean baseline fasting blood glucose concentrations were significantly higher among participants in the placebo group compared with the Se group (96.6±14.6 and 92.3±12.0, respectively; p=0.04), a trend which remained through the 20 min assessment.ConclusionsThese findings do not support a significant adverse effect of daily Se supplementation with 200 µg/day of selenized yeast on β-cell function or insulin sensitivity as an explanation for previously reported associations between Se and T2D. Further clarification of longer term effects of Se is needed.Clinical trial registryNIH Clinical Trials.gov numberNCT00078897.

Adherence to the American Cancer Society&rsquo, s (ACS) Nutrition and Physical Activity Cancer Prevention Guidelines is associated with reductions in overall cancer incidence and mortality, including site-specific cancers such as colorectal cancer. We examined the relationship between baseline adherence to the ACS guidelines and (1) baseline adenoma characteristics and (2) odds of recurrent colorectal adenomas over 3 years of follow-up. Cross-sectional and prospective analyses with a pooled sample of participants from the Wheat Bran Fiber (n = 503) and Ursodeoxycholic Acid (n = 854) trials were performed. A cumulative adherence score was constructed using baseline self-reported data regarding body size, diet, physical activity and alcohol consumption. Multivariable logistic regression demonstrated significantly reduced odds of having three or more adenomas at baseline for moderately adherent (odds ratio [OR] = 0.67, 95% confidence intervals [CI]: 0.46&ndash, 0.99) and highly adherent (OR = 0.50, 95% CI: 0.31&ndash, 0.81) participants compared to low adherers (p-trend = 0.005). Conversely, guideline adherence was not associated with development of recurrent colorectal adenoma (moderate adherence OR = 1.16, 95% CI: 0.85&ndash, 1.59, high adherence OR = 1.23, 95% CI: 0.85&ndash, 1.79).

BACKGROUND: Selenium, an essential trace element, has been investigated as a potential cancer prevention agent. However, several studies have indicated that selenium supplementation may be associated with an increased risk of type 2 diabetes (T2D), although an equivocal relation of this nature requires confirmation. OBJECTIVE: We examined the association between baseline plasma concentrations of selenium and the prevalence of T2D, as well as whether participant characteristics or intake of other antioxidant nutrients modified this relation. METHODS: We conducted cross-sectional analyses of 1727 participants from the Selenium Trial, a randomized clinical trial of selenium supplementation for colorectal adenoma chemoprevention that had data for baseline selenium plasma concentrations, T2D status, and dietary intake. Logistic regression modeling was used to evaluate the associations between plasma selenium concentrations and prevalent T2D, adjusting for confounding factors. Heterogeneity of effect by participant characteristics was evaluated utilizing likelihood-ratio tests. RESULTS: Mean ± SD plasma selenium concentrations for those with T2D compared with those without T2D were 143.6 ± 28.9 and 138.7 ± 27.2 ng/mL, respectively. After adjustment for confounding, higher plasma selenium concentrations were associated with a higher prevalence of T2D, with ORs (95% CIs) of 1.25 (0.80, 1.95) and 1.77 (1.16, 2.71) for the second and third tertiles of plasma selenium, respectively, compared with the lowest tertile (P-trend = 0.007). No significant effect modification was observed for age, sex, body mass index, smoking, or ethnicity. Increased odds of T2D were seen among those who were in the highest tertile of plasma selenium and the highest category of intake of β-cryptoxanthin (P-trend = 0.03) and lycopene (P-trend = 0.008); however, interaction terms were not significant. CONCLUSIONS: These findings show that higher plasma concentrations of selenium were significantly associated with prevalent T2D among participants in a selenium supplementation trial. Future work is needed to elucidate whether there are individual characteristics, such as blood concentrations of other antioxidants, which may influence this relation.

We describe our approach to develop a sampling frame for slum and non-slum areas using satellite data for an impact evaluation of a reproductive health and family planning program in six cities of Uttar Pradesh, India. The methods used in the paper were developed as part of the Measurement, Learning & Evaluation project (MLE) of the Urban Health Initiative (UHI) program in Uttar Pradesh (UP), India. Increasing access and use of high-quality modern family planning services, particularly among the urban poor, is a primary goal of UHI. Family planning use is associated with lower maternal and child mortality rates, and unintended pregnancies (Cates, Contraception 81(6):460–461, 2010; Cleland et al., Lancet 368(9549):1810–1827, 2006, Lancet 380(9837):149–156, 2012). To evaluate the UHI program in UP, India, a total of six cities were selected for the impact evaluation: Agra, Aligarh, Allahabad, Gorakhpur, Moradabad and Varanasi. This paper describes the methodology developed to design a representative population-based sample of slum and non-slum areas to be surveyed before, during and at the end of UHI program implementation to capture behavior changes among the urban poor, slum and non-slum residents. Geographic data for slums was obtained from the Remote Sensing Applications Center (RSAC). These data were combined with road networks, administrative boundary data and remotely sensed imagery to delineate the study cities into slum and non-slum primary sampling units using Geographic Information Systems.

Drugs that inhibit cyclooxygenase (COX)-2 and the metabolism of arachidonic acid (ARA) to prostaglandin E2 are potent anti-inflammatory agents used widely in the treatment of joint and muscle pain. Despite their benefits, daily use of these drugs has been associated with hypertension, cardiovascular and gastrointestinal toxicities. It is now recognized that ARA is metabolized to a number of bioactive oxygenated lipids (oxylipins) by cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP450) enzymes. Currently, the contribution of individual variability in ARA metabolism in response to the COX-2 inhibitors and potential adverse effects remains poorly understood. Using patient samples from the randomized, placebo-controlled phase III selenium/celecoxib (Sel/Cel) trial for the prevention of colorectal adenomatous polyps, we analyzed plasma concentrations of 74 oxylipins in a subset of participants who received celecoxib (n = 90) or placebo (n = 95). We assessed the effect of celecoxib (with and without low dose aspirin) on circulating oxylipins and systolic blood pressure (SBP). Individual CYP450- and LOX- but not COX-derived metabolites were higher with celecoxib than placebo (P