Background:Metabolomic changes related to colorectal cancer (CRC) may serve as diagnostic markers to identify patients may develop or have developed CRC. Methods:Untargeted lipidomics were performed on serum from CRC cases and clean-colon controls from the Chicago Colorectal Cancer Consortium (CCCC) and the University of Arizona Cancer Center (UACC). Results:Untargeted lipidomics in the CCCC CRC series revealed significant alterations in sphingolipids. Targeted lipidomics revealed a signature of five sphingomyelins (SMs) were significantly decreased in CRC patients in CCCC and UACC CRC series. Circulating SMs are degraded primarily by S-SMase and serum S-SMase activity was significantly higher in UACC cases as compared to controls. Serum S-SMase activity was also measured in two series of adenoma patients to determine if S-SMase may serve as a biomarker for development of colorectal neoplasia. While S-SMase activity was significantly higher in adenoma patients compared to controls in the mostly white UACC series, S-SMase activity in samples from the Chicago Black series (CCCC) were indistinguishable from each other and significantly higher than UACC controls. Conclusions:Together, these studies suggest the potential for S-SMase activity to serve as a biomarker for colorectal neoplasia, with potential implications in some but perhaps not all populations.

With the death on July 29, 2023 of David Alberts, known far and wide as Dave, the cancer research community lost a true colossus. His interests over the years spanned the clinical pharmacology of anticancer drugs, the treatment of women's cancers, and cancer prevention. His contributions in each field garnered international recognition. At the same time, Dave mentored numerous individuals at every career stage, assumed multiple leadership roles at his own institution and beyond. Remarkably, he always remained a busy physician providing extraordinary care to countless patients.Dave was born in Milwaukee on December 30, 1939, where first-cousin Bruce Alberts describes the cousins growing up in a large extended family. The death from cancer of another cousin, Reed, at the age of 20, provided the inspiration for Dave to become a cancer physician. After Shorewood High School in Milwaukee, he attended Trinity College, Hartford, CT, before obtaining his MD from the University of Virginia (Charlottesville, VA). After Medicine Internship at the University of Wisconsin, Madison (Madison, WI), he became a Clinical Associate in Pharmacology at NIH/NCI and then completed his Medicine Residency at the University of Minnesota (Minneapolis, MN). He then moved to the University of California, San Francisco (UCSF; San Francisco, CA) for further training in clinical pharmacology and medical oncology. On one illustrious rotation at UCSF, Dave was the oncology fellow, Frank Meyskens the resident, and Dan Von Hoff the intern; all three would later be Directors of NCI Cancer Centers. Dave remained on faculty at UCSF until recruited in 1975 by Sydney Salmon to the recently created University of Arizona Cancer Center (UACC; Tucson, AZ), his academic home for the rest of his career.From a groundbreaking report of the pharmacokinetics of daunorubicin in humans while training at NCI and work on cytotoxic agents for the treatment of myeloma at UCSF, Dave quickly progressed to gain recognition for his work at UACC on the efficacy and clinical pharmacology of commonly used and investigational cytotoxic agents. Agents studied by Bob Dorr and others in the Alberts lab included bleomycin, chlorambucil, cisplatin, cyclophosphamide, and melphalan. Most of the agents first required de novo development of assays to measure tissue and body-fluid levels. During this period, Dave developed his interest in novel therapies for gynecologic cancers.Dave's major contributions to improving gynecologic cancer outcomes derived from a combination of his scientific creativity and leadership roles in the Southwest Oncology Group, the Gynecologic Oncology Group, and other large groups that he steadily accrued. Setsuko Chambers comments that he was an early proponent in the 1980s of intraperitoneal chemotherapy for ovarian cancer, which later became a mainstay of treatment. He helped to lead early studies that established the benefits of maintenance therapy for patients with ovarian cancer, now the standard of care.Dave managed to keep both individual and community/population in mind: he always thought holistically about the individual patient with cancer, all the while seeking to reduce society's overall cancer burden. He was in the vanguard in his steady determination to persuade the cancer research community to focus on preventive measures to reduce cancer morbidity and mortality as well as on therapeutic advances for advanced disease. He initiated studies of chemotherapy-related cognitive impairment in patients with ovarian cancer. In 1989, he became the inaugural Director of UACC's Cancer Prevention and Control Program, which he led to national prominence over the next 16 years.Chemoprevention was considered a field of great promise in the 1980s and 1990s. Once again, Dave was an early leader in what was, for him, a new field of research. He chaired a key NCI committee on chemoprevention and started a colorectal cancer prevention program funded by NCI at UACC in the late 1980s; he led this for nearly two decades before handing over to one of us (P. Lance). The program endures, now under the leadership of Beth Jacobs. Three phase III randomized controlled chemoprevention trials in a combined total of over 4,000 patients were completed from 1990 to 2013. Using colorectal adenoma as a surrogate endpoint for colorectal cancer, the primary outcome in each trial was a comparison of the development of new/metachronous adenoma in patients receiving intervention versus placebo.Although all three trials had null outcomes, thanks to Dave's trial design the material collected from participants—including a meticulously annotated biobank—is a rich resource for ancillary studies that has yielded over 90 publications to date. Topics include dietary and other lifestyle risk factors for colorectal adenoma; genome-wide association studies of metachronous adenoma risk; response to selenium supplementation; selenium supplementation and risk for type 2 diabetes; and modeling of incident adenoma characteristics to determine best-practice surveillance colonoscopy intervals.Arizona has among the highest rates of skin cancer in the world; their prevention was a natural focus for Dave. In the 1980s and 1990s, he completed the first phase II randomized trial of isoretinoin for advanced head and neck squamous cell carcinoma (SCC) and led the retinoid skin cancer prevention (SKICAP) trial. These trials were pivotal in establishing the use of systemic retinoids as part of usual preventive care for transplant and other patients with severe skin photodamage or a history of multiple cutaneous SCC.In the late 1990s, Dave started an NCI-funded Skin Cancer Prevention program with Tim Bowden, focusing on novel chemoprevention strategies. Melanotan-1 was developed and first brought to the clinic through the program and is now FDA approved for use in patients with porphyria. Painstaking dissection of the mechanistic roles of the MAPK and PI3K pathways in the development of cutaneous SCC was another important contribution. The program continues—Dave's legacy in action—under the leadership of Clara Curiel.As an index of Dave's extramural support, when the journal Science “took a look at the people at the top of the funding heap” in 2001, Dave was one of the three “top-funded clinical, social science PIs” in the entire NIH portfolio. Now in its fourth edition, his book Fundamentals of Cancer Prevention (Heidelberg: Springer), co-edited with Lisa Hess, is testimony to his preeminence in the cancer prevention field.Advising and mentoring activities were inextricably woven into Dave's research. He found time to supervise an astonishing number of masters and PhD students, postdoctoral fellows, and junior faculty. In assiduously supporting the career interests of women he was, as usual, ahead of his time. Many of those whom Dave advised early in their careers went on to leadership roles in academic organizations and industry, including two who became Directors of NCI Comprehensive Cancer Centers.Three decades of dedication to the institution culminated in Dave's appointment as UACC Director from 2005 to 2013. During his tenure, the UACC Skin Cancer Institute was founded and major new clinic buildings were established in Tucson and Phoenix. He was proud and protective of UACC's role as the only NCI Cancer Center headquartered in Arizona and championed its mission to serve the whole state; as Director, he led a statewide NCI-supported partnership for cancer prevention with the Native American community.Dave's prominence in the cancer research community-at-large reflected his accomplishments at home. He served on the External Advisory Committees of many of the country's largest NCI Cancer Centers and as a member of the NCI's Board of Scientific Advisors. He was Co-Editor-in-Chief of Cancer Epidemiology Biomarkers and Prevention with one of us (J. Potter) from 2003 to 2008. He was a joy to work with, thoughtful about the careers of young researchers, nurturing their output, always with an eye on opportunities to teach and mentor.Among many honors, The University of Arizona (Tucson, AZ) awarded Dave its highest academic honor of Regents Professor. He received AACR's Eighth Annual H. Burchenal Clinical Research Award and the Second Annual Pioneer Award in Cancer Prevention as well as the 2004 American Society of Preventive Oncology's Joseph F. Fraumeni Jr Distinguished Achievement Award.What an extraordinary combination of humility, passion, commitment, humanity, and wisdom we have lost in Dave Alberts! Janine Einspahr observes that he had a talent for pulling together exceptional groups of researchers for projects/grants. Jeff Trent tells us that Dave—suffering from Valley Fever, tied to IVs, and in his hospital gown—successfully defended a P01 project. His legacy includes many scientists who will continue the work of cancer prevention and cancer treatment, walking in Dave's footsteps and cutting new paths. At the beating heart of Dave's entire career was his role as a dedicated physician, practicing until the day he retired and sustaining his practice tirelessly during years of heavy administrative responsibilities. His commitment to his patients was unique and legendary; it included indiscriminately providing his cell-phone number. He was so available to so many!One can only understand how Dave scaled the professional heights that he did by appreciating his irrepressible wife Heather of 60 years, their children Tim and Sabrina and their spouses, and Dave and Heather's five grandchildren. There was no boundary between Dave's professional and family lives—and Heather was omnipresent in Dave's professional life. Dave is truly irreplaceable.No disclosures were reported.

Introduction:Leveraging cancer screening tests, such as the fecal immunochemical test (FIT), that allow for self-sampling and postal mail for screening invitations, test delivery, and return can increase participation in colorectal cancer (CRC) screening. The range of approaches that use self-sampling and mail for promoting CRC screening, including use of recommended best practices, has not been widely investigated. Methods:We characterized self-sampling and mail strategies used for implementing CRC screening across a consortium of 8 National Cancer Institute Cancer Moonshot Initiative Accelerating Colorectal Cancer Screening and Follow-up through Implementation Science (ACCSIS) research projects. These projects serve diverse rural, urban, and tribal populations in the US. Results:All 8 ACCSIS projects leveraged self-sampling and mail to promote screening. Strategies included organized mailed FIT outreach with mailed invitations, including FIT kits, reminders, and mailed return (n = 7); organized FIT-DNA outreach with mailed kit return (n = 1); organized on-demand FIT outreach with mailed offers to request a kit for mailed return (n = 1); and opportunistic FIT-DNA with in-clinic offers to be mailed a test for mailed return (n = 2). We found differences in patient identification strategies, outreach delivery approaches, and test return options. We also observed consistent use of Centers for Disease Control and Prevention Summit consensus best practice recommendations by the 7 projects that used mailed FIT outreach. Conclusion:In research projects reaching diverse populations in the US, we observed multiple strategies that leverage self-sampling and mail to promote CRC screening. Mail and self-sampling, including mailed FIT outreach, could be more broadly leveraged to optimize cancer screening.

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

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

Background Selenium (Se) is a trace element that has been investigated as a potential chemopreventive agent for colorectal cancer. Dietary intake of other antioxidant nutrients may modify the effect of Se. Objective We examined the association between intake and serum concentrations of retinol, beta-carotene, beta-cryptoxanthin, lycopene, lutein/zeaxanthin, and alpha- and gamma-tocopherol and the development of metachronous colorectal adenoma, and if these nutrients modified the effect of Se. Methods We conducted a prospective study of 1874 participants from the Se Trial with data for antioxidant intake, as well as a subcohort of 508 participants with serum biomarker concentrations. Results Statistically significantly lower odds for the development of metachronous adenoma were observed for those participants in the highest tertile of intake for lutein/zeaxanthin compared to the lowest, with an OR (95% CI) of 0.72 (0.56-0.94). No effect modification for intake of any nutrient was observed. However, circulating concentrations of lycopene exhibited statistically significant effect modification of selenium supplementation (p < 0.06), Conclusion These findings show that intake and circulating concentrations of antioxidant nutrients were not consistently associated with reduced odds for the development of metachronous lesions, although blood concentrations of lycopene may modify the effect of selenium supplementation.

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

Supplementary Figure 1. Gut microbial composition and diversity in patients with and without adenomas. A) Microbial composition was similar between groups across all taxonomic levels. The groups did not differ in terms of α-diversity: B) observed number of operational taxonomic units (OTUs) or C) the Shannon diversity index. The groups did not cluster by β-diversity: D) unweighted and E) weighted UniFrac distance metrics.

Abstract 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 FAT3 gene, rs61901554, showed a suggestive association (P = 1.10 × 10−6) and was associated with advanced adenomas in CORSA (P = 0.04). Two intronic variants, rs12728998 and rs6699944 in NLRP3 were also observed to have suggestive associations with metachronous lesions (P = 2.00 × 10−6) in the Selenium Trial and were associated with advanced adenoma in CORSA (P = 0.03). Our results provide new areas of investigation for the genetic basis of the development of metachronous colorectal adenoma and support a role for FAT3 involvement in the Wnt/β-catenin pathway leading to colorectal neoplasia. Trial Registration number: NCT00078897 (ClinicalTrials.gov).

Abstract Multiple myeloma (MM) is a malignancy of plasma cells in the bone marrow and the second most common hematological malignancy. MM is characterized by a high degree of heterogeneity and has a hereditary genetic component with relatives of MM patients having a higher risk of disease development. Additionally, MM displays a disparity in occurrence and mortality among sexes with males having a higher risk than females. Although new therapies have significantly improved survival rates, MM remains incurable as most patients experience relapses. Therefore, understanding the genetic control underlying complex outcomes is important for the development of better treatments for MM patients. While the majority of research has been focusing on protein-coding regions of the genome, recent studies have started to illuminate the role of non-coding variations on MM. For example, many of the 176 GWAS risk loci associated with MM susceptibility are located within or adjacent to regulatory regions, indicating a role in transcriptional regulation. However, how the non-coding genetic variations affect gene expression, tumor etiology and outcome is poorly understood. To better understand the genetic and biological underpinnings of MM, we utilize genomic approaches to examine non-coding germline and somatic effects on gene expression and cancer outcome. First, we analyzed whole-genome sequencing (WGS) from peripheral blood and WGS and RNA-seq from baseline tumor specimens of 607 participants from the CoMMpass longitudinal study of the Multiple Myeloma Research Foundation. Using both joint and sex-stratified analyses, we detected 6,504 unique germline variants associated with changes in gene expression, i.e. expression quantitative trait loci (eQTLs), corresponding to 4,598 unique eGenes. Among the identified eQTLs, 33.76% exhibit sex-specific effects and 654 variants are associated with genes that influence survival in the CoMMpass cohort. In addition to the germline eQTLs, we identified 266 somatic eQTLs, corresponding to 208 eGenes. Among the identified eQTLs, 566 germline and 88 somatic eQTLs overlap with an ATACseq peak in MM cell lines. Second, we selected a set of eQTLs to validate their functions in transcriptional activity in MM cell lines (2 females, 2 males) using CRISPR interference screens (CRISPRi) with a scRNA-seq readout. By analyzing global transcriptional changes, we identify potential downstream targets that may play essential roles in MM genesis and progression. In conclusion, using computational and functional genomics approaches, we have identified germline and somatic eQTLs that are associated with gene expression and survival in MM, thus providing insights into how these non-coding variations contribute to tumor etiology and outcome. Citation Format: Linh T. Bui, Heini M. Natri, Lance M. Peter, Bianca Argente, Austin J. Gutierrez, Arnold Federico, Mei-I Chung, Jonathan Keats, Nicholas E. Banovich. Functions of genetic variation on gene expression and survival in multiple myeloma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5780.

Abstract 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.

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.

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.

Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 (COVID-19) and poor outcomes. Here, we analyze the transcriptomes of 611,398 single cells isolated from healthy and CLD lungs to identify molecular characteristics of lung cells that may account for worse COVID-19 outcomes in patients with chronic lung diseases. We observe a similar cellular distribution and relative expression of SARS-CoV-2 entry factors in control and CLD lungs. CLD AT2 cells express higher levels of genes linked directly to the efficiency of viral replication and the innate immune response. Additionally, we identify basal differences in inflammatory gene expression programs that highlight how CLD alters the inflammatory microenvironment encountered upon viral exposure to the peripheral lung. Our study indicates that CLD is accompanied by changes in cell-type-specific gene expression programs that prime the lung epithelium for and influence the innate and adaptive immune responses to SARS-CoV-2 infection.

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 during and 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.

According to the Institute of Medicine’s National Cancer Policy Forum, the American Cancer Society, and the National Cancer Institute, cancer screening programs are partly responsible for declining colorectal cancer (CRC) incidence and mortality rates in the U.S. Unfortunately, American Indians (AIs) have experienced either no change or an increase in CRC incidence and mortality, disproportionate diagnosis of late stage disease and poorer survival. While, nearly two-thirds of U.S. adults are current with United States Preventive Services Task Force (USPSTF) guidelines for CRC screening, AI screening rates range from only 28% to 51% in the Southwest and Southern Plains regions. One evidence-based intervention strategy for increasing CRC screening recommended by the Community Preventive Services Task Force (CPSTF) is patient navigation. By offering interpretation, transportation, social support, and culturally and linguistically appropriate education and outreach, patient navigators are able to reduce structural barriers and facilitate access to screening. While researchers have documented effectiveness of patient navigation towards enhancing cancer screening among AI populations, few studies have elucidated best practices for training patient navigators to serve in this capacity. As an effort of the AI CRC Screening Consortium formed by the National Cancer Institute-Designated Cancer Centers at the Universities of Arizona, New Mexico, and Oklahoma, we trained a cadre of 21 individuals to serve as patients navigators in six unique AI-serving health clinics and communities in Oklahoma, Arizona, and New Mexico. We used a unique blend of didactic and interactive training components (i.e. role playing, games, and group dialogues). The 2.5-day curriculum centered upon a set of nine modules that included digestive system anatomy, USPSTF CRC screening guidelines, stool-based test procedures, direct visualization test procedures, CRC risk factors, CRC diagnosis and treatment, Transtheoretical Model and Motivational Interviewing, and patient navigation tips. A 36-item pre-/post-test was administered to assess the impact of training upon navigator capacity. Paired-sample t-tests were utilized to analyze mean differences in scales measuring two key constructs – CRC-specific knowledge and self-efficacy to engage in CRC control efforts. Evaluation findings demonstrated statistically significance increases in both CRC knowledge scores (pre-test mean = 7.8/12.0 vs. post-test mean 10.9/12.0, p=0.000) and self-efficacy scores (pre-test mean = 3.8/5.0 vs. post-test mean = 4.8/5.0, p=0.001). These findings demonstrate the value of robust capacity development activities with patient navigators prior to intervention as a means of not only increase knowledge about CRC and its associated screenings, but to also engender significant readiness and confidence among patient navigators to integrate CRC control into practice. Citation Format: Kevin C English, Cheyenne Jim, Jennifer Hatcher, Mark P Doescher, Shiraz I Mishra, Peter Lance, Dorothy Rhoades, Usha Menon. Capacity development among patient navigators to enhance colorectal cancer control in American Indian-serving healthcare facilities in the U.S. Southwest and Southern Plains [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 B004.

Background Fertility intentions and contraceptive use are often used to demonstrate gaps in programs and policies to meet the contraceptive needs of women and couples. Prior work demonstrated that fertility intentions are fluid and change over a woman's (or couple's) life course with changing marital status, childbearing, and education/employment opportunities. This study uses longitudinal data to better examine the fluidity of women's fertility intentions and disentangle the complex interrelationships between fertility and contraceptive use. Methods Using survey data from three time points and three urban sites in Senegal, this study examines how women's fertility intentions and contraceptive use in an earlier period affect pregnancy experience and the intentionality of experienced pregnancies among a sample of 1050 women who were in union at all three time points. We apply correlated random effect longitudinal regression methods to predict a subsequent birth by fertility intentions and modern contraceptive use at an earlier period addressing endogeneity concerns of earlier analyses that only include two time periods. Results Descriptive results demonstrate some change in fertility desires over time such that 6-8% of women who reported their pregnancy as intended (i.e., wanted to get pregnant at time of pregnancy) reported earlier that they did not want any(more) children. Multivariate analyses demonstrate that women who want to delay or avoid a pregnancy and are using modern contraception are the least likely to get pregnant. Among women who became pregnant, the only factor differentiating whether the pregnancy is reported as intended or unintended (mistimed or unwanted) was prior fertility intention. Women who wanted to delay a pregnancy previously were more likely to report the pregnancy as unintended compared to women who wanted to get pregnant soon. Conclusions These results suggest some post-hoc rationalization among women who are getting pregnant. Women who say they do not want to get pregnant may be choosing not to use a contraceptive method in this urban Senegal context of high fertility. Programs seeking to reach these women need to consider their complex situations including their fertility intentions, family planning use, and the community norms within which they are reporting these intentions and behaviors.

Christine L Sardo Molmenti*,1,2 , Elizabeth A Hibler3 , Jingyan Yang4, Jennifer M Kolb5 , Jane Yang6, Maryam Hussain2, Shaneda Warren Andersen7, Nitin Shivappa8,9,10 , James R Hébert8,9,10 , Peter Lance11 , David S Alberts12,13, Alfred I Neugut4,14,15 & Elizabeth T Jacobs12,13 1Department of Occupational Medicine, Epidemiology & Prevention, Donald & Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY 11549, USA 2Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA 3Division of Epidemiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA 4Mailman School of Public Health, Columbia University, New York, NY 10032, USA 5Division of Gastroenterology & Hepatology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA 6Department of Surgery, Northwell Health, Manhasset, NY 10032, USA 7Department of Population Health Sciences, School of Medicine & Public Health, University of Wisconsin-Madison, WI 53726, USA 8Department of Epidemiology & Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208, USA 9Cancer Prevention & Control Program, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208, USA 10Connecting Health Innovations LLC, Columbia, SC 29201, USA 11Department of Molecular & Cellular Biology, University of Arizona, Tucson, AZ 85721, USA 12Mel & Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ 85724, USA 13University of Arizona Comprehensive Cancer Center, Tucson, AZ 85724, USA 14Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY 10032, USA 15Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University Medical Center, New York, NY 10032, USA *Author for correspondence: cmolmenti@northwell.edu

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.