Elizabeth T Jacobs

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• Habila, M. A., Valencia, D. Y., Khan, S. M., Heslin, K. M., Hoskinson, J., Ernst, K. C., Pogreba-Brown, K., Jacobs, E. T., Cordova-Marks, F. M., & Warholak, T. (2022). A Rasch analysis assessing the reliability and validity of the Arizona CoVHORT COVID-19 vaccine questionnaire. SSM - population health, 17, 101040.
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  Despite the widespread availability of COVID-19 vaccines in the United States, many that have chosen not to be vaccinated have done so because of vaccine hesitancy. This highlights the need for tools that accurately capture the knowledge, attitudes, and beliefs towards COVID-19 vaccines, and provide steps toward improving vaccine acceptance.
• Khan, S. M., Farland, L. V., Catalfamo, C. J., Austhof, E., Bell, M. L., Chen, Z., Cordova-Marks, F., Ernst, K. C., Garcia-Filion, P., Heslin, K. M., Hoskinson, J., Jehn, M. L., Joseph, E. C., Kelley, C. P., Klimentidis, Y., Russo Carroll, S., Kohler, L. N., Pogreba-Brown, K., & Jacobs, E. T. (2022). Elucidating symptoms of COVID-19 illness in the Arizona CoVHORT: a longitudinal cohort study. BMJ open, 12(1), e053403.
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  To elucidate the symptoms of laboratory-confirmed COVID-19 cases as compared with laboratory-confirmed negative individuals and to the untested general population among all participants who reported symptoms within a large prospective cohort study.
• Khan, S. M., Shilen, A., Heslin, K. M., Ishimwe, P., Allen, A. M., Jacobs, E. T., & Farland, L. V. (2022). SARS-CoV-2 infection and subsequent changes in the menstrual cycle among participants in the Arizona CoVHORT study. American journal of obstetrics and gynecology, 226(2), 270-273.
• Batai, K., Trejo, M. J., Chen, Y., Kohler, L. N., Lance, P., Ellis, N. A., Cornelis, M. C., Chow, H. S., Hsu, C. H., & Jacobs, E. T. (2021). Genome-Wide Association Study of Response to Selenium Supplementation and Circulating Selenium Concentrations in Adults of European Descent. The Journal of nutrition, 151(2), 293-302.
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  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.
• Bell, M. L., Catalfamo, C. J., Farland, L. V., Ernst, K. C., Jacobs, E. T., Klimentidis, Y. C., Jehn, M., & Pogreba-Brown, K. (2021). Post-acute sequelae of COVID-19 in a non-hospitalized cohort: Results from the Arizona CoVHORT. PloS one, 16(8), e0254347.
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  Clinical presentation, outcomes, and duration of COVID-19 has ranged dramatically. While some individuals recover quickly, others suffer from persistent symptoms, collectively known as long COVID, or post-acute sequelae of SARS-CoV-2 (PASC). Most PASC research has focused on hospitalized COVID-19 patients with moderate to severe disease. We used data from a diverse population-based cohort of Arizonans to estimate prevalence of PASC, defined as experiencing at least one symptom 30 days or longer, and prevalence of individual symptoms. There were 303 non-hospitalized individuals with a positive lab-confirmed COVID-19 test who were followed for a median of 61 days (range 30-250). COVID-19 positive participants were mostly female (70%), non-Hispanic white (68%), and on average 44 years old. Prevalence of PASC at 30 days post-infection was 68.7% (95% confidence interval: 63.4, 73.9). The most common symptoms were fatigue (37.5%), shortness-of-breath (37.5%), brain fog (30.8%), and stress/anxiety (30.8%). The median number of symptoms was 3 (range 1-20). Amongst 157 participants with longer follow-up (≥60 days), PASC prevalence was 77.1%.
• Catalfamo, C. J., Heslin, K. M., Shilen, A., Khan, S. M., Hunsaker, J. R., Austhof, E., Barraza, L., Cordova-Marks, F. M., Farland, L. V., Garcia-Filion, P., Hoskinson, J., Jehn, M., Kohler, L. N., Lutrick, K., Harris, R. B., Chen, Z., Klimentidis, Y. C., Bell, M. L., Ernst, K. C., , Jacobs, E. T., et al. (2021). Design of the Arizona CoVHORT: A Population-Based COVID-19 Cohort. Frontiers in public health, 9, 620060.
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  This study is a prospective, population-based cohort of individuals with a history of SARS-CoV-2 infection and those without past infection through multiple recruitment sources. The main study goal is to track health status over time, within the diverse populations of Arizona and to identify the long-term consequences of COVID-19 on health and well-being. A total of 2,881 study participants (16.2% with a confirmed SARS-CoV-2 infection) have been enrolled as of December 22, 2020, with a target enrollment of 10,000 participants and a planned follow-up of at least 2 years. This manuscript describes a scalable study design that utilizes a wide range of recruitment sources, leveraging electronic data collection to capture and link longitudinal participant data on the current and emerging issues associated with the COVID-19 pandemic. The cohort is built within a collaborative infrastructure that includes new and established partnerships with multiple stakeholders, including the state's public universities, local health departments, tribes, and tribal organizations. Challenges remain for ensuring recruitment of diverse participants and participant retention, although the electronic data management system and timing of participant contact can help to mitigate these problems.
• Florea, A., Jacobs, E. T., Harris, R. B., Klimentidis, Y. C., Thajudeen, B., & Kohler, L. N. (2021). Chronic kidney disease unawareness and determinants using 1999-2014 National Health and Nutrition Examination Survey Data. Journal of public health (Oxford, England).
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  Although chronic kidney disease (CKD) affects 15% of the United States (US) population,
• Habila, M. A., Kimaru, L. J., Mantina, N., Valencia, D. Y., McClelland, D. J., Musa, J., Madhivanan, P., Sagay, A., & Jacobs, E. T. (2021). Community-Engaged Approaches to Cervical Cancer Prevention and Control in Sub-Saharan Africa: A Scoping Review. Frontiers in global women's health, 2, 697607.
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  Cervical cancer remains one of the top causes of cancer mortality among African women. Cervical cancer screening and early detection and treatment of precancer is one of the evidence-based interventions to reduce incidence and mortality. The application of community-based participatory research (CBPR) has been used in the United States to improve participation in screening and reduce cervical cancer disparities. However, it is unclear whether these engaged approaches have been used in sub-Saharan African to address disparities related to cervical cancer mortality. Highlight community engagement in cervical cancer prevention and control in Sub-Saharan Africa (SSA), describe the community engagement efforts that are currently being used, and to describe the best practices for community engagement toward the end-goal of cervical cancer prevention and control. We searched PubMed, Embase, CINHAL, African Journals Online (AJOL), and African Index Medicus-WHO from inception until June 8, 2020. After screening 620 titles and abstracts, and reviewing 56 full-text articles according to inclusion and exclusion criteria, 9 articles met the selection criteria and were included. Relevant data variables were extracted from the included articles and a narrative synthesis was performed. Between 2005 and 2019, 9 articles describing research in Ghana, Kenya, Zambia, Senegal, South Africa, and Nigeria were included. These articles described work that largely took place in rural settings predominantly among women age 15-65 years. Leveraging community networks such as community health workers, religious organizations, traditional leaders, and educational institutions increased awareness of cervical cancer. Working within existing social structures and training community members through the research effort were promising methods for addressing the disparities in cervical cancer incidence and mortality among communities. The findings of this scoping review have contributed to the understanding of which novel approaches to community-based practices can be used to address cervical cancer disparities among SSA communities that carry a disproportionate disease burden. Community engagement in the research process, while effortful, has shown to be beneficial to researchers and to the communities that they serve, and provides valuable next steps in the effort to address cervical cancer disparities in SSA.
• Lent, A. B., Mohan, P., Derksen, D., Cance, W. G., Barraza, L., Jacobs, E. T., & Calhoun, E. A. (2021). The association between breast cancer capacity and resources with incidence and mortality in Arizona's low populous counties. Rural and remote health, 21(3), 6357.
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  While cancer deaths have decreased nationally, declines have been much slower in rural areas than in urban areas. Previous studies on rural cancer service capacity are limited to specific points along the cancer care continuum (eg screening, diagnosis or treatment) and require updating to capture the current rural health landscape since implementation of the 2010 Affordable Care Act in the USA. The association between current rural cancer service capacity across the cancer care continuum and cancer incidence and death is unclear. This cross-sectional study explored the association between breast cancer service capacity and incidence and mortality in Arizona's low populous counties.
• Martinez, J. A., Skiba, M. B., Chow, H. S., Chew, W. M., Saboda, K., Lance, P., Ellis, N. A., & Jacobs, E. T. (2021). A Protective Role for Arachidonic Acid Metabolites against Advanced Colorectal Adenoma in a Phase III Trial of Selenium. Nutrients, 13(11).
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  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 ( = 256) at baseline and at 12-months. There were significantly lower odds of an advanced adenoma at baseline with higher prostaglandin E (PGE), 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 PGE ((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.
• Skiba, M. B., Jacobs, E. T., Crane, T. E., Kopp, L. M., & Thomson, C. A. (2021). Relationship Between Individual Health Beliefs and Fruit and Vegetable Intake and Physical Activity Among Cancer Survivors: Results from the Health Information National Trends Survey. Journal of adolescent and young adult oncology.
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  The aim of this study was to describe diet and physical activity (PA) behaviors and health beliefs among cancer survivors and identify potential differences between adolescent and young adult (AYA) and adult/older cancer survivors. Cancer survivors ( = 1864) participating in the Health Information National Trends Survey (HINTS) provided responses regarding diet and PA and selected health beliefs related to general health and cancer (self-efficacy, attitudinal belief, normative belief, risk belief, intention, and self-regulation). Health belief associations with diet and PA were assessed using adjusted logistic regression models, and multiple linear regression was used for a computed Modified American Cancer Society Adherence score (0-10, higher score indicates higher adherence to recommendations); age at diagnosis was evaluated as a potential effect modifier. Health behaviors between AYA and adult/older were not significantly different; a greater percent of AYA met fruit and resistance PA recommendations. Higher health self-efficacy was associated with meeting aerobic PA recommendations (odds ratio [OR]: 1.71; confidence interval [95% CI]: 1.13-2.60;  = 0.01). Higher intention was inversely related to meeting vegetable recommendation (OR: 0.58; 95% CI: 0.35-0.97;  = 0.04). Self-regulation was associated with higher odds of meeting each recommendation. Self-efficacy and self-regulation were associated with greater adherence ( = 0.52 ± 0.16,  = 0.001;  = 1.21 ± 0.24,  
• Aristizabal, P., Sherer, M., Perdomo, B., Castelao, E., Thornburg, C., Proudfoot, J., Jacobs, E. T., Newfield, R. S., Zage, P., Roberts, W., & Martinez, M. E. (2020). Sociodemographic and clinical characteristics associated with vitamin D status in newly diagnosed pediatric cancer patients. Pediatr Hematol Oncol, 37(4). doi:doi: 10.1080/08880018.2020.1721629
• Florea, A., Harris, R. B., Klimentidis, Y. C., Kohler, L. N., Jurutka, P. W., & Jacobs, E. T. (2020). Circulating Fibroblast Growth Factor-21 and Risk of Metachronous Colorectal Adenoma. Journal of gastrointestinal cancer.
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  Prior work has shown that higher circulating concentrations of fibroblast growth factor-21 (FGF-21) are associated with an increased likelihood of developing colorectal cancer. We conducted a prospective study to assess the relationship between circulating FGF-21 and odds of developing early neoplastic lesions in the colorectum.
• Jacobs, E. T., Foote, J. A., Kohler, L. N., Skiba, M. B., & Thomson, C. A. (2020). Re-examination of dairy as a single commodity in US dietary guidance. Nutrition reviews, 78(3), 225-234.
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  Dairy products have been a key component of dietary guidance in the United States for more than 100 years. In light of major advances in the understanding of dietary intake and metabolism, the aim of this review was to examine whether dairy should remain a single commodity in federal guidance. Considerations include recognizing that a substantial proportion of the world's adult population (65%-70%) exhibits lactase nonpersistence, a reduced ability to metabolize lactose to glucose and galactose. Shifts in the US population, including a greater proportion of African Americans and Asians, are of key importance because several studies have shown a markedly higher prevalence of lactase nonpersistence and, consequently, a lower dairy intake among these groups. While cow's milk alternatives are available, families who use them will pay up to an additional $1400 per year compared with those who are able to consume dairy products. Dietary guidance also contains downstream effects for government assistance, such as the US Department of Agriculture's National School Lunch Program and School Breakfast Program. For reasons like these, Canada has recently removed dairy as a separate food group in national dietary guidance. The results of the present review suggest that consideration of this modification when developing population-level guidelines in the United States is warranted.
• Molmenti, C., Hibler, E. A., Yang, J., Jennifer, K., Yang, J., Maryam, H., Shaneda, A., Nitin, S., James, H., Peter, L., Alberts, D., Al, N., & Jacobs, E. T. (2020). Characteristics of colorectal adenoma recurrence among individuals under 50 years of age compared to those 50 years of age or older.. Colorectal Cancer, 9(3). doi:doi/10.2217/crc-2020-0019
• Santos, E. M., Coalson, J. E., Munga, S., Agawo, M., Jacobs, E. T., Klimentidis, Y. C., Hayden, M. H., & Ernst, K. C. (2020). "After those nets are torn, most people use them for other purposes": an examination of alternative bed net use in western Kenya. Malaria journal, 19(1), 272.
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  Alternative long-lasting insecticidal net (LLIN) use for purposes other than sleeping protection from mosquitoes is widely debated as a limitation to successful malaria control efforts, yet rarely rigorously studied.
• Santos, E. M., McClelland, D. J., Shelly, C. E., Hansen, L., Jacobs, E. T., Klimentidis, Y. C., & Ernst, K. C. (2020). Malaria education interventions addressing bed net care and repair practices: a systematic review. Pathogens and global health, 114(1), 2-15.
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  Education intervention effectiveness to improve bed net care and repair knowledge or practices is unclear. To assess intervention effectiveness, we systematically reviewed eight peer-reviewed literature databases and 16 malaria organizations (PROSPERO protocol CRD42019123932) using pre-specified combinations of 'education intervention', 'mosquito net', and 'malaria' search terms. Data were abstracted for 29 of 43 studies meeting inclusion criteria, of which 16 studies included education as amain focus. Of these 16, there was evidence of intervention effectiveness among half of the studies, which reported improvements in knowledge or practices, while four had mixed results, and four had unclear results. Overall there is no clear conclusion regarding the effectiveness of education interventions to improve net care and repair, though some instructional methods suggest more success than others. Interventions used combinations of instructional methods; passive mass education (6), active mass education (12), and interpersonal methods (8). Interventions combining mass and interpersonal methods resulted in positive improvements (four positive, one mixed). We found no evidence that interventions grounded in health behavior theory achieved more positive results than those not grounded in theory, potentially because net care education was typically asecondary objective. Of 289 gray literature results, 286 (99%) were net distribution reports from Against Malaria Foundation describing 136 distributions; eighty of which (58.8%) mentioned no education related to net care and repair. We found lack of involvement of experts in education among included interventions. Involving trained instructors with expertise in education theory and instructional strategies may improve instruction quality to yield more effective interventions.
• Skiba, M. B., McElfresh, J. J., Howe, C. L., Crane, T. E., Kopp, L. M., Jacobs, E. T., & Thomson, C. A. (2020). Dietary Interventions for Adult Survivors of Adolescent and Young Adult Cancers: A Systematic Review and Narrative Synthesis. Journal of adolescent and young adult oncology.
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  Adolescent and young adult (AYA) cancer survivors, here defined as individuals diagnosed with cancer between 15 and 39 years of age, are at high risk for adverse late-term metabolic effects of treatment through adulthood. Diet is a modifiable lifestyle behavior that may improve metabolic health outcomes in AYA cancer survivors. However, the details of dietary interventions for this unique population remain largely undescribed. In this systematic review, we aim to synthesize the results of dietary interventions for adult AYA cancer survivors. Seven databases and clinical trial registries were searched in March 2019 for interventions targeting dietary behaviors in AYA cancer survivors (PROPSERO systematic review number: CRD42019126376). Descriptive statistics and a narrative synthesis were completed to detail intervention participants and components. After full text review of 233 studies, four studies met all inclusion criteria. All studies were heterogeneous for participant age, cancer type, and duration, and were designed for feasibility and preliminary efficacy. Included studies followed different dietary guidance; however, each resulted in a significant change on a primary outcome of either dietary quality or body composition. Three of the four studies included a theoretical framework, where self-efficacy was a central construct. Counseling, in person, telephone, or electronic, provided behavioral support. Results of this systematic review suggest high potential to change dietary behaviors in AYA, but interventions remain limited. AYA cancer survivors demonstrate unique physiological and psychosocial needs, and future interventions designed to address this care gap should be targeted for this population with consideration of social support, delivery mode, and individual tailoring.
• Trejo, M., Lishimpi, K., Kalima, M., Mwaba, C., Banda, L., Chuba, A., Chama, E., Msadabwe, S., Bell, M., Harris, R., Jacobs, E. T., & Soliman, A. (2020). Effects of HIV Status on Cervical Cancer Progression for Non-Metastatic Cervical Cancer Patients in Lusaka, Zambia.. International Journal of Gynecological Cancer, 30(5). doi:http://dx.doi.org/10.1136/ijgc-2019-000987
• Jacobs, E. T., Lance, P., Mandarino, L. J., Ellis, N. A., Chow, H. S., Foote, J., Martinez, J. A., Hsu, C. P., Batai, K., Saboda, K., & Thompson, P. A. (2019). Selenium supplementation and insulin resistance in a randomized, clinical trial. BMJ open diabetes research & care, 7(1), e000613.
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  While 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.
• Santos, E. M., Coalson, J. E., Jacobs, E. T., Klimentidis, Y. C., Munga, S., Agawo, M., Anderson, E., Stroupe, N., & Ernst, K. C. (2019). Bed net care practices and associated factors in western Kenya. Malaria journal, 18(1), 274.
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  Insecticide-treated nets (ITNs) and long-lasting insecticidal nets (LLINs) are effective for malaria prevention and are designed to provide nearly 5 years of mosquito protection. However, many ITNs and LLINs become damaged and ineffective for mosquito bite prevention within 1 to 2 years in field conditions. Non-adherence to recommended bed net care and repair practices may partially explain this shortened net longevity.
• Skiba, M. B., Kohler, L. N., Crane, T. E., Jacobs, E. T., Shadyab, A. H., Kato, I., Snetselaar, L., Qi, L., & Thomson, C. A. (2019). The Association between Prebiotic Fiber Supplement Use and Colorectal Cancer Risk and Mortality in the Women's Health Initiative. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 28(11), 1884-1890.
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  Fiber-based prebiotic supplements are marketed for maintaining bowel health and promoting beneficial gut bacteria. However, the association between prebiotic supplement use and colorectal cancer risk and mortality is unknown.
• Zhou, J., Jenkins, T. G., Jung, A. M., Jeong, K. S., Zhai, J., Jacobs, E. T., Griffin, S. C., Dearmon-Moore, D., Littau, S. R., Peate, W. F., Ellis, N. A., Lance, P., Chen, Y., & Burgess, J. L. (2019). DNA methylation among firefighters. PloS one, 14(3), e0214282.
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  Firefighters are exposed to carcinogens and have elevated cancer rates. We hypothesized that occupational exposures in firefighters would lead to DNA methylation changes associated with activation of cancer pathways and increased cancer risk. To address this hypothesis, we collected peripheral blood samples from 45 incumbent and 41 new recruit non-smoking male firefighters and analyzed the samples for DNA methylation using an Illumina Methylation EPIC 850k chip. Adjusting for age and ethnicity, we performed: 1) genome-wide differential methylation analysis; 2) genome-wide prediction for firefighter status (incumbent or new recruit) and years of service; and 3) Ingenuity Pathway Analysis (IPA). Four CpGs, including three in the YIPF6, MPST, and PCED1B genes, demonstrated above 1.5-fold statistically significant differential methylation after Bonferroni correction. Genome-wide methylation predicted with high accuracy incumbent and new recruit status as well as years of service among incumbent firefighters. Using IPA, the top pathways with more than 5 gene members annotated from differentially methylated probes included Sirtuin signaling pathway, p53 signaling, and 5' AMP-activated protein kinase (AMPK) signaling. These DNA methylation findings suggest potential cellular mechanisms associated with increased cancer risk in firefighters.
• Augustus, G. J., Roe, D. J., Jacobs, E. T., Lance, P., & Ellis, N. A. (2018). Is increased colorectal screening effective in preventing distant disease?. PloS One, 13(7), e0200462.
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  Screening in the average risk population for colorectal cancer (CRC) is expected to reduce the incidence of distant (i.e., metastatic) CRCs at least as much as less advanced CRCs. Indeed, since 2000, during which time colonoscopy became widely used as a screening tool, the overall incidence of CRC has been reduced by 29%.
• Jacobs, E. T., Burgess, J. L., & Abbott, M. B. (2018). The Donora Smog Revisited: 70 Years After the Event That Inspired the Clean Air Act. American Journal of Public Health, 108(S2), S85-S88.
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  At a storefront museum approximately 25 miles southeast of Pittsburgh, Pennsylvania, a sign reads, "Clean Air Started Here." This is not hyperbole. At the end of October 1948, the communities of Donora and Webster in Pennsylvania were visited by a smog that changed the face of environmental protection in the United States. Conservative estimates showed that 20 individuals died, while an additional 5900-43% of the population of Donora-were affected by the smog. This event led to the first large-scale epidemiological investigation of an environmental health disaster in the United States. Questions remain about the long-term effects of the smog, because higher rates of cardiovascular disease and cancer than were expected were observed in the region in the decade following the smog. Recent work has suggested that environmental contaminants from a bygone era in Donora might have an impact even today. In addition, reports regarding air pollution have indicated that levels of pollutants similar to those estimated to have occurred in Donora are currently present in some rapidly industrializing regions of China and India. Seventy years after the smog, this event still resonates.
• Jacobs, E. T., Gupta, S., Baron, J. A., Cross, A. J., Lieberman, D. A., Murphy, G., & Martínez, M. E. (2018). Family history of colorectal cancer in first-degree relatives and metachronous colorectal adenoma. American Journal of Gastroenterology, 113(6), 899-905.
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  Little is known about the relationship between having a first-degree relative (FDR) with colorectal cancer (CRC) and risk for metachronous colorectal adenoma (CRA) following polypectomy.
• Jeong, K. S., Zhou, J., Griffin, S. C., Jacobs, E. T., Dearmon-Moore, D., Zhai, J., Littau, S. R., Gulotta, J., Moore, P., Peate, W. F., Richt, C. M., & Burgess, J. L. (2018). MicroRNA Changes in Firefighters. Journal of Occupational and Environmental Medicine, 60(5), 469-474.
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  Firefighters have elevated cancer incidence and mortality rates. MicroRNAs play prominent roles in carcinogenesis, but have not been previously evaluated in firefighters.
• Jung, A. M., Dennis, L. K., Jacobs, E. T., & Wondrak, G. T. (2018). Sun sensitivity and sun protective behaviors during sun exposure among indoor office workers in the American Midwest. Photoderm Photoimmunol Photomed, 34(6), 393-399.
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  Sun sensitivity, a confounder between sun exposure and sun protection, is often overlooked. We examined how sun exposure and sun protection behaviors among indoor workers varied by sun sensitivity.
• Kohler, L. N., Florea, A., Kelley, C. P., Chow, S., Hsu, P., Batai, K., Saboda, K., Lance, P., & Jacobs, E. T. (2018). Higher Plasma Selenium Concentrations Are Associated with Increased Odds of Prevalent Type 2 Diabetes. The Journal of Nutrition, 148(8), 1333-1340.
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  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.
• Kohler, L. N., Foote, J., Kelley, C. P., Florea, A., Shelly, C., Chow, H. S., Hsu, P., Batai, K., Ellis, N., Saboda, K., Lance, P., & Jacobs, E. T. (2018). Selenium and Type 2 Diabetes: Systematic Review. Nutrients, 10(12).
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  Several studies have investigated the potential role of selenium (Se) in the development of type 2 diabetes (T2D) with disparate findings. We conducted a systematic review and meta-analysis to synthesize the evidence of any association between Se and T2D. PubMed, Embase, and Scopus were searched following the Preferred Reporting Items for Systematic Reviews and Meta-analysis Approach (PRISMA). Sixteen studies from 15 papers met inclusion criteria defined for this review. Of the 13 observational studies included, 8 demonstrated a statistically significant positive association between concentrations of Se and odds for T2D, with odds ratios (95% confidence intervals) ranging from 1.52 (1.01⁻2.28) to 7.64 (3.34⁻17.46), and a summary odds ratio (OR) (95% confidence interval (CI)) of 2.03 (1.51⁻2.72). In contrast, among randomized clinical trials (RCTs) of Se, a higher risk of T2D was not observed for those who received Se compared to a placebo (OR = 1.18, 95% CI 0.95⁻1.47). Taken together, the results for the relationship between Se and T2D differ between observational studies and randomized clinical trials (RCTs). It remains unclear whether these differences are the result of uncontrolled confounding in the observational studies, or whether there is a modest effect of Se on the risk for T2D that may vary by duration of exposure. Further investigations on the effects of Se on glucose metabolism are needed.
• Kohler, L. N., Harris, R. B., Oren, E., Roe, D. J., Lance, P., & Jacobs, E. T. (2018). Adherence to Nutrition and Physical Activity Cancer Prevention Guidelines and Development of Colorectal Adenoma. Nutrients, 10(8).
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  Adherence to the American Cancer Society'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 ( = 503) and Ursodeoxycholic Acid ( = 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]: 0.46⁻0.99) and highly adherent (OR = 0.50, 95% CI: 0.31⁻0.81) participants compared to low adherers (-trend = 0.005). Conversely, guideline adherence was not associated with development of recurrent colorectal adenoma (moderate adherence OR = 1.16, 95% CI: 0.85⁻1.59, high adherence OR = 1.23, 95% CI: 0.85⁻1.79).
• Pottinger, H. L., Jacobs, E. T., Haenchen, S. D., & Ernst, K. C. (2018). Parental attitudes and perceptions associated with childhood vaccine exemptions in high-exemption schools. PloS One, 13(6), e0198655.
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  Previous work demonstrates that individuals who obtain exemptions from school immunization requirements are geographically clustered, making regional differences in vaccination coverage a significant concern. Even where exemption levels are high, there are still parents that vaccinate. School-level assessments have determined that exemptors are more likely to attend wealthier schools with fewer minorities. Few studies have assessed divergent opinions within the context of a higher-exemption community to examine subtle differences in opinion surrounding vaccinations. Therefore, the objective of this work was to assess attitudes and perceptions towards vaccinations and compare them for exemptors and non-exemptors. We administered surveys to parents in high-exemption (>10%) elementary schools in Arizona during the 2012-13 school year. A total of 404 surveys were completed by parents among schools in Maricopa (n = 7) and Yavapai (n = 2) counties. Of these, 35% (n = 141) were exemptors and 65% (n = 261) were non-exemptors. Exemptors were more likely than non-exemptors to be concerned about serious side-effects (p
• Sardo Molmenti, C. L., Steck, S. E., Thomson, C. A., Hibler, E. A., Yang, J., Shivappa, N., Greenlee, H., Wirth, M. D., Neugut, A. I., Jacobs, E. T., & Hébert, J. R. (2017). Dietary Inflammatory Index and Risk of Colorectal Adenoma Recurrence: A Pooled Analysis. Nutrition and Cancer, 69(2), 238-247.
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  No studies have evaluated the association between the dietary inflammatory index (DII) and colorectal adenoma recurrence. DII scores were calculated from a baseline food frequency questionnaire. Participants (n = 1727) were 40-80 years of age, enrolled in two Phase III clinical trials, who had ≥1 colorectal adenoma(s) removed within 6 months of study registration, and a follow-up colonoscopy during the trial. Multiple logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). No statistically significant associations were found between DII and odds of colorectal adenoma recurrence [ORs (95% CIs) = 0.93 (0.73, 1.18) and 0.95 (0.73, 1.22)] for subjects in the second and third DII tertiles, respectively, compared to those in the lowest tertile (Ptrend = 0.72). No associations were found for recurrent colorectal adenoma characteristics, including advanced recurrent adenomas, large size, villous histology, or anatomic location. While our study did not support an association between a proinflammatory diet and colorectal adenoma recurrence, future studies are warranted to elucidate the role of a proinflammatory diet on the early stages of colorectal carcinogenesis.
• Batai, K., Murphy, A. B., Ruden, M., Newsome, J., Shah, E., Dixon, M. A., Jacobs, E. T., Hollowell, C. M., Ahaghotu, C., & Kittles, R. A. (2017). Race and BMI modify associations of calcium and vitamin D intake with prostate cancer. BMC cancer, 17(1), 64.
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  African Americans have disproportionately higher burden of prostate cancer compared to European Americans. However, the cause of prostate cancer disparities is still unclear. Several roles have been proposed for calcium and vitamin D in prostate cancer pathogenesis and progression, but epidemiologic studies have been conducted mainly in European descent populations. Here we investigated the association of calcium and vitamin D intake with prostate cancer in multiethnic samples.
• Gunn, J. K., Ehiri, J. E., Jacobs, E. T., Ernst, K. C., Pettygrove, S., Center, K. E., Osuji, A., Ogidi, A. G., Musei, N., Obiefune, M. C., Ezeanolue, C. O., & Ezeanolue, E. E. (2017). Prevalence of Caesarean sections in Enugu, southeast Nigeria: Analysis of data from the Healthy Beginning Initiative. PloS one, 12(3), e0174369.
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  In order to meet the Sustainable Development Goal to decrease maternal mortality, increased access to obstetric interventions such as Caesarean sections (CS) is of critical importance. As a result of women's limited access to routine and emergency obstetric services in Nigeria, the country is a major contributor to the global burden of maternal mortality. In this analysis, we aim to establish rates of CS and determine socioeconomic or medical risk factors associated with having a CS in Enugu, southeast Nigeria.
• Kohler, L. N., Hibler, E. A., Harris, R. B., Oren, E., Roe, D. J., Jurutka, P. W., & Jacobs, E. T. (2017). Greater Adherence to Cancer Prevention Guidelines Is Associated with Higher Circulating Concentrations of Vitamin D Metabolites in a Cross-Sectional Analysis of Pooled Participants from 2 Chemoprevention Trials. The Journal of nutrition, 147(3), 421-429.
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  Background: Several lifestyle factors targeted by the American Cancer Society (ACS) Nutrition and Physical Activity Cancer Prevention Guidelines are also associated with circulating concentrations of vitamin D metabolites. This suggests that greater adherence to the ACS guidelines may be related to better vitamin D status.Objective: We examined the relation between adherence to the ACS guidelines and circulating concentrations of 2 vitamin D metabolites, 25-hydroxycholecalciferol [25(OH)D] and 1α,25-dihydroxyvitamin D [1,25(OH)2D].Methods: We conducted cross-sectional analyses of pooled participants from the Wheat Bran Fiber (n = 503) and Ursodeoxycholic Acid (n = 854) trials. A cumulative adherence score was constructed with the use of baseline data on body size, diet, physical activity, and alcohol consumption. Continuous vitamin D metabolite concentrations and clinically relevant categories were evaluated with the use of multiple linear and logistic regression models, respectively.Results: The most adherent participants were more likely to be older, white, and nonsmokers than were the least adherent. A statistically significant association was observed between guideline adherence and concentrations of circulating 25(OH)D (means ± SEs-high adherence: 32.0 ± 0.8 ng/mL; low adherence: 26.4 ± 0.7 ng/mL; P-trend < 0.001). For 1,25(OH)2D concentrations, high adherence was again significantly related to greater metabolite concentrations, with mean ± SE concentrations of 36.3 ± 1.3 pg/mL and 31.9 ± 1.0 pg/mL for high- and low-adherers, respectively (P-trend = 0.008). Furthermore, the odds of attaining a sufficient 25(OH)D status were 4.37 times higher for those most adherent than for those least adherent (95% CI: 2.47, 7.71 times).Conclusion: These findings demonstrate that greater adherence to the ACS guidelines is associated with higher circulating concentrations of both of 25(OH)D and 1,25(OH)2D.
• Lance, P., Alberts, D. S., Thompson, P. A., Fales, L., Wang, F., San Jose, J., Jacobs, E. T., Goodman, P. J., Darke, A. K., Yee, M., Minasian, L., Thompson, I. M., & Roe, D. J. (2017). Colorectal Adenomas in Participants of the SELECT Randomized Trial of Selenium and Vitamin E for Prostate Cancer Prevention. Cancer Prevention Research, 10(1), 45-54.
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  Selenium and vitamin E micronutrients have been advocated for the prevention of colorectal cancer. Colorectal adenoma occurrence was used as a surrogate for colorectal cancer in an ancillary study to the Selenium and Vitamin E Cancer Prevention Trial (SELECT) for prostate cancer prevention. The primary objective was to measure the effect of selenium (as selenomethionine) on colorectal adenomas occurrence, with the effect of vitamin E (as α-tocopherol) supplementation on colorectal adenoma occurrence considered as a secondary objective. Participants who underwent lower endoscopy while in SELECT were identified from a subgroup of the 35,533 men randomized in the trial. Adenoma occurrence was ascertained from the endoscopy and pathology reports for these procedures. Relative Risk (RR) estimates and 95% confidence intervals (CI) of adenoma occurrence were generated comparing those randomized to selenium versus placebo and to vitamin E versus placebo based on the full factorial design. Evaluable endoscopy information was obtained for 6,546 participants, of whom 2,286 had 1+ adenomas. Apart from 21 flexible sigmoidoscopies, all the procedures yielding adenomas were colonoscopies. Adenomas occurred in 34.2% and 35.7%, respectively, of participants whose intervention included or did not include selenium. Compared with placebo, the RR for adenoma occurrence in participants randomized to selenium was 0.96 (95% CI, 0.90-1.02; P = 0.194). Vitamin E did not affect adenoma occurrence compared with placebo (RR = 1.03; 95% CI, 0.96-1.10; P = 0.38). Neither selenium nor vitamin E supplementation can be recommended for colorectal adenoma prevention. Cancer Prev Res; 10(1); 45-54. ©2016 AACR.
• Sabir, M. S., Khan, Z., Hu, C., Galligan, M. A., Dussik, C. M., Mallick, S., Stone, A. D., Batie, S. F., Jacobs, E. T., Whitfield, G. K., Haussler, M. R., Heck, M. C., & Jurutka, P. W. (2017). SIRT1 enzymatically potentiates 1,25-dihydroxyvitamin D3 signaling via vitamin D receptor deacetylation. The Journal of steroid biochemistry and molecular biology, 172, 117-129.
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  The hormonal metabolite of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D), binds to the vitamin D receptor (VDR) and promotes heterodimerization of VDR with a retinoid-X-receptor (RXR) to genomically regulate diverse cellular processes. Herein, it is revealed for the first time that VDR is post-translationally acetylated, and that VDR immunoprecipitated from human embryonic kidney (HEK293) cells displays a dramatic decrease in acetylated receptor in the presence of 1,25D-ligand, sirtuin-1 (SIRT1) deacetylase, or the resveratrol activator of SIRT1. To elucidate the functional significance of VDR deacetylation, vitamin-d-responsive-element (VDRE)-based transcriptional assays were performed to determine if deacetylase overexpression affects VDR/VDRE-driven transcription. In HEK293 kidney and TE85 bone cells, co-transfection of low amounts (1-5ng) of a SIRT1-expression vector elicits a reproducible and statistically significant enhancement (1.3- to 2.6-fold) in transcription mediated by VDREs from the CYP3A4 and cyp24a1 genes, where the magnitude of response to 1,25D-ligand is 6- to 30-fold. Inhibition of SIRT1 via EX-527, or utilization of a SIRT1 loss-of-function mutant (H363Y), resulted in abrogation of SIRT1-mediated VDR potentiation. Studies with a novel, non-acetylatable VDR mutant (K413R) showed that the mutant VDR possesses enhanced responsiveness to 1,25D, in conjunction with reduced, but still significant, sensitivity to exogenous SIRT1, indicating that acetylation of lysine 413 is relevant, but that other acetylated residues in VDR contribute to modulation of its activity. We conclude that the acetylation of VDR comprises a negative feedback loop that attenuates 1,25D-VDR signaling. This regulatory loop is reversed by SIRT1-catalyzed deacetylation of VDR to amplify VDR signaling and 1,25D actions.
• Haenchen, S., Hayden, M., Dickinson, K., Walker, K. R., Jacobs, E. T., Brown, H. E., Gunn, J., Kohler, L., & Ernst, K. C. (2015). Mosquito avoidance practices and knowledge of arboviral diseases in cities with differing recent history of disease. American Journal of Tropical Medicine and Hygiene.
• Jacobs, E. T., Haussler, M. R., Alberts, D. S., Kohler, L. N., Lance, P., Martínez, M. E., Roe, D. J., & Jurutka, P. W. (2016). Association between Circulating Vitamin D Metabolites and Fecal Bile Acid Concentrations. Cancer prevention research (Philadelphia, Pa.), 9(7), 589-97.
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  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.
• Jacobs, E. T., Kohler, L. N., Kunihiro, A. G., & Jurutka, P. W. (2016). Vitamin D and Colorectal, Breast, and Prostate Cancers: A Review of the Epidemiological Evidence. Journal of Cancer, 7(3), 232-40.
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  Over the past two decades, the question of whether vitamin D has a role in cancer incidence, progression, and mortality has been studied in detail. Colorectal, breast, and prostate cancers have been a particular area of focus; together, these three malignancies account for approximately 35% of cancer cases and 20% of cancer deaths in the United States, and as such are a major public health concern. Herein, we review and synthesize the epidemiological research regarding vitamin D, as measured by the biomarker 25-hydroxycholecalciferol [25(OH)D], and the incidence, progression, and mortality of these cancers. Overall, the results of observational studies of the relationship between 25(OH)D and colorectal cancer have revealed a consistent inverse association for incidence and mortality; while for breast cancer, results have generally demonstrated a relationship between higher 25(OH)D and lower risk for progression and mortality. In contrast, randomized, double-blind clinical trials conducted to date have generally failed to support these findings. For prostate cancer, there is no convincing evidence of an association between 25(OH)D and incidence, and inconsistent data for progression and mortality, though results of one open label clinical trial suggest that supplementation with 4000 IU/d of vitamin D3 may inhibit progression of the disease. Nonetheless, until the results of additional ongoing randomized, double-blind clinical trials are reported, it will be difficult to ascertain if vitamin D itself is related to a reduction in risk for some cancer endpoints, or whether high concentrations of the vitamin D biomarker 25(OH)D may instead serve as a marker for an overall beneficial risk factor profile.
• Kohler, L. N., Garcia, D. O., Harris, R. B., Oren, E., Roe, D. J., & Jacobs, E. T. (2016). Adherence to Diet and Physical Activity Cancer Prevention Guidelines and Cancer Outcomes: A Systematic Review. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 25(7), 1018-28.
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  Many studies have reported that adherence to health promotion guidelines for diet, physical activity, and maintenance of healthy body weight may decrease cancer incidence and mortality. A systematic review was performed to examine associations between adherence to established cancer prevention guidelines for diet and physical activity and overall cancer incidence and mortality. PubMed, Google Scholar, and Cochrane Reviews databases were searched following the current recommendations of Preferred Reporting Items for Systematic Reviews and Meta-analysis Approach (PRISMA). Twelve studies met inclusion criteria for this review. High versus low adherence to established nutrition and physical activity cancer prevention guidelines was consistently and significantly associated with decreases of 10% to 61% in overall cancer incidence and mortality. Consistent significant reductions were also shown for breast cancer incidence (19%-60%), endometrial cancer incidence (23%-60%), and colorectal cancer incidence in both men and women (27%-52%). Findings for lung cancer incidence were equivocal, and no significant relationships were found between adherence and ovarian or prostate cancers. Adhering to cancer prevention guidelines for diet and physical activity is consistently associated with lower risks of overall cancer incidence and mortality, including for some site-specific cancers. Cancer Epidemiol Biomarkers Prev; 25(7); 1018-28. ©2016 AACR.
• Kohler, L. N., Kohler, L. N., Garcia, D. O., Garcia, D. O., Harris, R. B., Harris, R. B., Oren, E., Oren, E., Roe, D., Roe, D., Jacobs, E. T., & Jacobs, E. T. (2016). Adherence to Diet and Physical Activity Cancer Prevention Guidelines and Cancer Outcomes: A Systematic Review.. Cancer Epidemiology, Biomarkers & Prevention.
• Liu, L., Messer, K., Baron, J. A., Lieberman, D. A., Jacobs, E. T., Cross, A. J., Murphy, G., Martinez, M. E., & Gupta, S. (2016). A prognostic model for advanced colorectal neoplasia recurrence. Cancer causes & control : CCC, 27(10), 1175-85.
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  Following colonoscopic polypectomy, US Multisociety Task Force (USMSTF) guidelines stratify patients based on risk of subsequent advanced neoplasia (AN) using number, size, and histology of resected polyps, but have only moderate sensitivity and specificity. We hypothesized that a state-of-the-art statistical prediction model might improve identification of patients at high risk of future AN and address these challenges.
• Thompson, P. A., Ashbeck, E. L., Roe, D. J., Fales, L., Buckmeier, J., Wang, F., Bhattacharyya, A., Hsu, C., Chow, H. H., Ahnen, D. J., Boland, C. R., Heigh, R. I., Fay, D. E., Hamilton, S. R., Jacobs, E. T., Martinez, M. E., Alberts, D. S., & Lance, P. (2016). Selenium Supplementation for Prevention of Colorectal Adenomas and Risk of Associated Type 2 Diabetes. Journal of the National Cancer Institute, 108(12).
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  Selenium supplementation may help to prevent colorectal cancer; as precursors of colorectal cancer, colorectal adenomas are a surrogate for colorectal cancer. Selenium supplementation may increase risk of type 2 diabetes (T2D).
• Thompson, P. A., Ashbeck, E. L., Roe, D. J., Fales, L., Buckmeier, J., Wang, F., Bhattacharyya, A., Hsu, C., Chow, S. H., Ahnen, D. J., Boland, C. R., Heigh, R. I., Fay, D. E., Hamilton, S. R., Jacobs, E. T., Martinez, E. M., Alberts, D. S., & Lance, P. (2016). Celecoxib for the Prevention of Colorectal Adenomas: Results of a Suspended Randomized Controlled Trial. Journal of the National Cancer Institute, 108(12).
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  Cyclooxygenase (COX)-2 inhibitors such as celecoxib were designed to preserve anti-inflammatory activity without inhibiting COX-1. Downregulation of COX-2 inhibits colorectal carcinogenesis.
• Bea, J. W., Jurutka, P. W., Hibler, E. A., Lance, P., Martínez, M. E., Roe, D. J., Sardo Molmenti, C. L., Thompson, P. A., & Jacobs, E. T. (2015). Concentrations of the vitamin D metabolite 1,25(OH)2D and odds of metabolic syndrome and its components. Metabolism: clinical and experimental, 64(3), 447-59.
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  Few epidemiological studies have investigated the association between circulating concentrations of the active vitamin D metabolite 1,25(OH)2D and metabolic syndrome. We sought to determine whether blood levels of 1,25(OH)2D are associated with metabolic syndrome and its individual components, including waist circumference, triglycerides, blood pressure, and glucose, and high-density lipoprotein. We also investigated these associations for the more abundant precursor vitamin D metabolite, 25(OH)D.
• Dampf Stone, A., Batie, S. F., Sabir, M. S., Jacobs, E. T., Lee, J. H., Whitfield, G. K., Haussler, M. R., & Jurutka, P. W. (2015). Resveratrol potentiates vitamin D and nuclear receptor signaling. Journal of cellular biochemistry, 116(6), 1130-43.
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  The 1,25-dihydroxyvitamin D3 (1,25D) hormone is derived from vitamin D generated in skin or obtained from the diet, and binds to and activates the vitamin D receptor (VDR) in target tissues including kidney, colon/small intestine, and bone/muscle. We tested resveratrol for its ability to modulate VDR signaling, using vitamin D responsive element (VDRE) and mammalian 2-hybrid (M2H) transcriptional system technology. Via VDRE-based assays in kidney, colon and myoblast cells, VDR-mediated transcription was activated by resveratrol, and a cooperative effect on transactivation was observed with resveratrol plus 1,25D. The M2H assay revealed a modest, resveratrol-induced dimerization of VDR with its retinoid X receptor (RXR) heteropartner. Cells treated with both resveratrol and 1,25D displayed synergistic stimulation of VDR-RXR heterodimerization, while resveratrol antagonized rexinoid-mediated RXR-RXR homodimerization. Increased transactivation in response to resveratrol was also observed with a subset of other nuclear receptors and their respective cognate responsive elements. Evaluation of wild-type versus a ligand-binding domain mutant VDR revealed that hormone-responsiveness to 1,25D was severely depressed, while the response to resveratrol was only moderately attenuated. Moreover, radiolabeled 1,25D-displacement assays demonstrated an increase in VDR-bound 1,25D in the presence of resveratrol. Thus, resveratrol may affect VDR and other nuclear receptors indirectly, likely via the ability of resveratrol to: (1) potentiate 1,25D binding to VDR; (2) activate RXR; and/or (3) stimulate SIRT1, an enzyme known to deacetylate nuclear receptors. The results of this study elucidate a possible pathway for crosstalk between two nutritionally derived lipids, vitamin D and resveratrol, both of which converge on VDR signaling.
• Gunn, J. K., Ehiri, J. E., Jacobs, E. T., Ernst, K. C., Pettygrove, S., Kohler, L. N., Haenchen, S. D., Obiefune, M. C., Ezeanolue, C. O., Ogidi, A. G., & Ezeanolue, E. E. (2015). Population-based prevalence of malaria among pregnant women in Enugu State, Nigeria: the Healthy Beginning Initiative. Malaria journal, 14(1), 438.
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  Malaria adversely affects pregnant women and their fetuses or neonates. Estimates of the malaria burden in pregnant women based on health facilities often do not present a true picture of the problem due to the low proportion of women delivering at these facilities in malaria-endemic regions.
• Gupta, S., Jacobs, E. T., Baron, J. A., Lieberman, D. A., Murphy, G., Ladabaum, U., Cross, A. J., Jover, R., Liu, L., & Martinez, M. E. (2015). Risk stratification of individuals with low-risk colorectal adenomas using clinical characteristics: a pooled analysis. Gut.
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  For individuals with 1-2 small (
• Haussler, M. R., Whitfield, G. K., Jurutka, P. W., Jacobs, E. T., Batie, S. F., Sabir, M. S., Lee, J. H., & Dampf Stone, A. -. (2015). Resveratrol potentiates vitamin D and nuclear receptor signaling. Journal of Cellular Biochemistry, 116, 14. doi:10.1002/jcb.25070
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  This paper should really count for 2015 since we heard about its acceptance in late December (technically now in press).
• Haussler, M. R., Whitfield, G. K., Jurutka, P. W., Jacobs, E. T., Batie, S. F., Sabir, M. S., Lee, J. H., Dampf Stone, A. -., Haussler, M. R., Whitfield, G. K., Jurutka, P. W., Jacobs, E. T., Batie, S. F., Sabir, M. S., Lee, J. H., & Dampf Stone, A. -. (2015). Resveratrol potentiates vitamin D and nuclear receptor signaling. Journal of Cellular Biochemistry, 116, 1130-1143. doi:DOI 10.1002/jcb.25070
• Hibler, E. A., Klimentidis, Y. C., Jurutka, P. W., Kohler, L. N., Lance, P., Roe, D. J., Thompson, P. A., & Jacobs, E. T. (2015). CYP24A1 and CYP27B1 Polymorphisms, Concentrations of Vitamin D Metabolites, and Odds of Colorectal Adenoma Recurrence. Nutrition and cancer, 67(7), 1131-41.
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  Development of colorectal adenoma and cancer are associated with low circulating 25-hydroxyvitamin D [25(OH)D] levels. However, less is known regarding colorectal neoplasia risk and variation in CYP27B1 or CYP24A1, genes encoding the enzymes responsible for the synthesis and catabolism of 1α,25-hydroxyvitamin D [1,25(OH)2D]. This study examined associations between CYP27B1 and CYP24A1 polymorphisms, circulating 25(OH)D and 1,25(OH)2D concentrations, and colorectal adenoma recurrence in a pooled sample from 2 clinical trials (n = 1,188). Nominal associations were observed between increasing copies of the T allele in CYP24A1 rs927650 and 25(OH)D concentrations (P = 0.02); as well as colorectal adenoma recurrence, with odds ratios (95% confidence intervals) of 1.30 (0.99-1.70) and 1.38 (1.01-1.89) for heterozygotes and minor allele homozygotes, respectively (P = 0.04). In addition, a statistically significant relationship between CYP24A1 rs35051736, a functional polymorphism, and odds for advanced colorectal adenoma recurrence was observed (P < 0.001). Further, nominally statistically significant interactions were observed between rs2296241 and 25(OH)D as well as rs2762939 and 1,25(OH)2D (P(interaction) = 0.10, respectively). Overall, CYP24A1 polymorphisms may influence the development of advanced lesions, and modify the effect of vitamin D metabolites on adenoma recurrence. Further study is necessary to characterize the differences between circulating vitamin D metabolite measurements compared to cellular level activity in relation to cancer risk.
• Hibler, E. A., Sardo Molmenti, C. L., Dai, Q., Kohler, L. N., Warren Anderson, S., Jurutka, P. W., & Jacobs, E. T. (2015). Physical activity, sedentary behavior, and vitamin D metabolites. Bone, 83, 248-255.
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  Physical activity is associated with circulating 25-hydroxyvitamin D (25(OH)D). However, the influence of activity and/or sedentary behavior on the biologically active, seco-steroid hormone 1α,25-dihydroxyvitamin D (1,25(OH)2D) is unknown. We conducted a cross-sectional analysis among ursodeoxycholic acid (UDCA) randomized trial participants (n=876) to evaluate associations between physical activity, sedentary behavior, and circulating vitamin D metabolite concentrations. Continuous vitamin D metabolite measurements and clinical thresholds were evaluated using multiple linear and logistic regression models, mutually adjusted for either 1,25(OH)2D or 25(OH)D and additional confounding factors. A statistically significant linear association between 1,25(OH)2D and moderate-vigorous physical activity per week was strongest among women (β (95% CI): 3.10 (1.51-6.35)) versus men (β (95% CI): 1.35 (0.79-2.29)) in the highest tertile of activity compared to the lowest (p-interaction=0.003). Furthermore, 25(OH)D was 1.54ng/ml (95% CI 1.09-1.98) higher per hour increase in moderate-vigorous activity (p=0.001) and odds of sufficient 25(OH)D status was higher among physically active participants (p=0.001). Sedentary behavior was not significantly associated with either metabolite in linear regression models, nor was a statistically significant interaction by sex identified. The current study identified novel associations between physical activity and serum 1,25(OH)2D levels, adjusted for 25(OH)D concentrations. These results identify the biologically active form of vitamin D as a potential physiologic mechanism related to observed population-level associations between moderate-vigorous physical activity with bone health and chronic disease risk. However, future longitudinal studies are needed to further evaluate the role of physical activity and vitamin D metabolites in chronic disease prevention.
• Jacobs, E. T., & Mullany, C. J. (2015). Vitamin D deficiency and inadequacy in a correctional population. Nutrition (Burbank, Los Angeles County, Calif.), 31(5), 659-63.
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  Adequate nutrition among inmates at correctional facilities may prevent a variety of diseases and conditions. Vitamin D is a nutrient of particular interest to incarcerated populations; however, research in this area is sparse. Therefore, the aim of this study was to assess vitamin D status among inmates in a prison in southern Arizona, a sun-replete region of the United States.
• Haenchen, S. D., Jacobs, E. T., Bratton, K. N., Carman, A. S., Oren, E., Pottinger, H. L., Regan, J. A., & Ernst, K. C. (2014). Perceptions of personal belief vaccine exemption policy: a survey of Arizona vaccine providers. Vaccine, 32(29), 3630-5.
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  As exemptions to school-entry requirements rise, vaccination rates in Arizona school children are approaching levels that may threaten public health. Understanding the interactions physicians have with vaccine-hesitant parents, as well as the opinions physicians hold regarding vaccination, exemption, and exemption policies, are critical to our understanding of, and ability to affect, vaccination exemption rates among children.
• Hibler, E. A., Jacobs, E. T., Stone, A. D., Sardo, C. L., Galligan, M. A., & Jurutka, P. W. (2014). Associations between vitamin D-binding protein isotypes, circulating 25(OH)D levels, and vitamin D metabolite uptake in colon cancer cells. Cancer prevention research (Philadelphia, Pa.), 7(4), 426-34.
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  Vitamin D metabolites have been extensively studied as cancer chemopreventive agents. Gc-globulin (GC) isotypes, based on rs7041 and rs4588 diplotypes, have varying affinities for 1α,25-dihydroxyvitamin D (1,25(OH)2D) and 25-hydroxyvitamin D (25(OH)D), which may affect circulating metabolite concentration as well as delivery at the cellular level. We evaluated associations between GC isotype and circulating vitamin D metabolite concentrations in 403 ursodeoxycholic acid (UDCA) clinical trial participants. Metabolite uptake was evaluated in human colon cancer (HCT-116) cells treated with ethanol vehicle, 1,25(OH)2D, or 25(OH)D, and with plasma from individuals with known GC isotype. Mammalian-2-hybrid and vitamin D-responsive element-based luciferase assays were used to measure the vitamin D receptor pathway activation as a marker for metabolite uptake. Regression analysis demonstrated significantly lower serum 25(OH)D concentration for clinical trial participants with 1F_2, 1S_2, or 2_2 isotypes (P < 0.01) compared with 1S_1S. Consistent with these in vivo observations, cellular data revealed that 25(OH)D uptake varied less by GC isotype only at the higher concentration tested (P = 0.05), while 1,25(OH)2D uptake differed markedly by GC isotype across concentration and assay (P < 0.01). The 1F_1S and 1F_2 isotypes produced the greatest reporter gene induction with 1,25(OH)2D treatment and, while activation varied less with 25(OH)D, the 2_2 isotype demonstrated increased induction at the lower concentration. These results suggest that vitamin D metabolite concentration and delivery to colon cells may vary not only by GC isotype, but also that certain isotypes may more effectively deliver 1,25(OH)2D versus 25(OH)D. Overall, these results may help identify populations at risk for cancer and potential recipients of targeted chemoprevention.
• Hibler, E. A., Molmenti, C. L., Lance, P., Jurutka, P. W., & Jacobs, E. T. (2014). Associations between circulating 1,25(OH)₂D concentration and odds of metachronous colorectal adenoma. Cancer causes & control : CCC, 25(7), 809-17.
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  Cellular-level studies demonstrate that the availability of the secosteroid hormone 1α,25-dihydroxyvitamin D [1,25(OH)2D] to colon cells promotes anti-carcinogenic activities. Although epidemiological data are relatively sparse, suggestive inverse trends have been reported between circulating 1,25(OH)2D concentration and colorectal neoplasia. We therefore sought to evaluate the relationship between circulating 1,25(OH)2D concentrations and odds for metachronous colorectal adenomas among 1,151 participants from a randomized trial of ursodeoxycholic acid for colorectal adenoma prevention. No relationship between 1,25(OH)2D and overall odds for metachronous lesions was observed, with ORs (95% CIs) of 0.80 (0.60-1.07) and 0.81 (0.60-1.10) for participants in the second and third tertiles, respectively, compared with those in the lowest (p-trend = 0.17). However, a statistically significant inverse association was observed between circulating 1,25(OH)2D concentration and odds of proximal metachronous adenoma, with an OR (95% CI) of 0.71 (0.52-0.98) for individuals in the highest tertile of 1,25(OH)2D compared with those in the lowest (p-trend = 0.04). While there was no relationship overall between 1,25(OH)2D and metachronous distal lesions, there was a significantly reduced odds for women, but not men, in the highest 1,25(OH)2D tertile compared with the lowest (OR 0.53; 95% CI 0.27-1.03; p-trend = 0.05; p-interaction = 0.08). The observed differences in associations with proximal and distal adenomas could indicate that delivery and activity of vitamin D metabolites in different anatomic sites in the colorectum varies, particularly by gender. These results identify novel associations between 1,25(OH)2D and metachronous proximal and distal colorectal adenoma, and suggest that future studies are needed to ascertain potential mechanistic differences in 1,25(OH)2D action in the colorectum.
• Molmenti, C. L., Hibler, E. A., Ashbeck, E. L., Thomson, C. A., Garcia, D. O., Roe, D., Harris, R. B., Lance, P., Cisneroz, M., Martinez, M. E., Thompson, P. A., & Jacobs, E. T. (2014). Sedentary behavior is associated with colorectal adenoma recurrence in men. Cancer causes & control : CCC, 25(10), 1387-95.
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  The association between physical activity and colorectal adenoma is equivocal. This study was designed to assess the relationship between physical activity and colorectal adenoma recurrence.
• Birnbaum, M. S., Jacobs, E. T., Ralston-King, J., & Ernst, K. C. (2013). Correlates of high vaccination exemption rates among kindergartens. Vaccine, 31(5).
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  The present study was designed to characterize Arizona schools with high rates of permanent PBE among kindergartners, and to determine the degree to which they aggregate across the state.
• Jacobs, E. T., Hibler, E. A., Lance, P., Sardo, C. L., & Jurutka, P. W. (2013). Association between circulating concentrations of 25(OH)D and colorectal adenoma: a pooled analysis. International journal of cancer. Journal international du cancer, 133(12).
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  The relationship between the biomarker of vitamin D status, 25(OH)D, and the risk for colorectal neoplasia is suggestive but equivocal. Questions remain regarding whether there are differential associations between 25(OH)D and colorectal adenoma by gender, colorectal subsite or features of baseline and recurrent adenomas. We sought to investigate the relationship between 25(OH)D and both baseline and recurrent adenoma characteristics. Our study was conducted among 2,074 participants in a pooled population of two clinical intervention trials of colorectal adenoma recurrence. A cross-sectional analysis of 25(OH)D and baseline adenoma characteristics and a prospective study of recurrent adenomas and their characteristics were conducted. There was a statistically significant inverse association between the concentrations of 25(OH)D and the presence of three or more adenomas at baseline. Compared to participants with 25(OH)D levels of
• Jacobs, E. T., Thomson, C. A., Flatt, S. W., Newman, V. A., Rock, C. L., & Pierce, J. P. (2013). Correlates of 25-hydroxyvitamin D and breast cancer stage in the Women's Healthy Eating and Living Study. Nutrition and cancer, 65(2).
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  Inverse associations between circulating 25-hydroxyvitamin D [25(OH)D] and breast cancer stage have been reported, thus it is critical to understand the variables that contribute to 25(OH)D levels among women with breast cancer. Among 904 women in the Women's Healthy Eating and Living Study, plasma 25(OH)D concentrations were measured and data on demographic characteristics, diet, physical activity, and tumor characteristics were collected at study entry. Statistically significant associations with 25(OH)D concentrations were observed for body mass index (BMI), body surface area (BSA), height, smoking, total vitamin D intake, physical activity, and race or ethnicity. Of the correlates of 25(OH)D, BMI, BSA, height, physical activity, and study site were associated with stage of breast cancer; however, concentrations of 25(OH)D were not significantly related to stage. In fully adjusted logistic regression models, the ORs (95% CIs) for the association between vitamin D deficiency and Stage II and III cancers were 0.85 (0.59-1.22) and 1.23 (0.71-2.15), respectively (P trend = 0.59), compared to Stage I. This study confirms previous work regarding the correlates of 25(OH)D concentrations but does not provide support for an association between vitamin D status and breast cancer stage.
• Jacobs, E. T., Van Pelt, C., Forster, R. E., Zaidi, W., Hibler, E. A., Galligan, M. A., Haussler, M. R., & Jurutka, P. W. (2013). CYP24A1 and CYP27B1 polymorphisms modulate vitamin D metabolism in colon cancer cells. Cancer research, 73(8).
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  Vitamin D is a well-studied agent for cancer chemoprevention and treatment. Its chief circulating metabolite, 25-hydroxyvitamin D, is converted into the active hormone 1,25-dihydroxyvitamin D (1,25D) by the cytochrome P450 enzyme CYP27B1 in kidney and other tissues. 1,25D is then deactivated by CYP24A1 and ultimately catabolized. Colorectal carcinoma cells express CYP27B1 and CYP24A1 that locally regulate 1,25D with potential implications for its impact on carcinogenesis. While 1,25D inhibits cancer growth, the effects of polymorphic variations in genes encoding proteins involved in 1,25D homeostasis are poorly understood. Using an RXR-VDR mammalian two-hybrid (M2H) biologic assay system, we measured vitamin D metabolite uptake and activation of the vitamin D receptor (VDR) pathway in colon cancer cells that expressed one of five CYP27B1 single-nucleotide polymorphisms (SNP) or four CYP24A1 SNPs. Compared with the wild-type control, four of five CYP27B1 SNPs reduced enzymatic activity, whereas one (V166L) increased activity. For CYP24A1, all tested SNPs reduced enzyme activity. Quantitative real-time PCR analyses supported the results of M2H experiments. The observed SNP-directed variation in CYP functionality indicated that vitamin D homeostasis is complex and may be influenced by genetic factors. A comprehensive understanding of 1,25D metabolism may allow for a more personalized approach toward treating vitamin D-related disorders and evaluating risk for carcinogenesis.
• Jacobs, E., Sardo, C. L., Kitzmiller, J. P., Apseloff, G., Harris, R. B., Roe, D. J., Stoner, G. D., & Jacobs, E. T. (2013). An Open-Label Randomized Crossover Trial of Lyophilized Black Raspberries on Postprandial Inflammation in Older Overweight Males: A Pilot Study. American journal of therapeutics.
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  This study was a 14-day, outpatient, open-label randomized crossover trial of lyophilized black raspberries (BRBs) in older overweight or obese males to determine whether BRB consumption affects postprandial inflammation associated with consumption of a high-fat high-calorie (HFHC) meal. Ten study participants consumed 45 g/d of lyophilized BRBs for 4 days, followed by a HFHC breakfast plus BRBs on day 6 or consumed the HFHC breakfast on day 6 without previous consumption of BRBs and then crossed over to the other treatment after a 2-day washout period. Blood samples were obtained before and 1, 2, 4, 8, and 12 hours after consumption of the HFHC breakfast. The primary study outcomes were changes in area under the concentration-time curve (AUC) for interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α). The secondary outcomes were safety and tolerability of lyophilized BRB powder. The chronology and values of measured serum concentrations for IL-6, TNF-α, and CRP were consistent with those described previously by other investigators. The AUC of serum IL-6 was lowered significantly (P = 0.03, n = 10) with BRB consumption (34.3 ± 7.6 pg·mL·h compared with 42.4 ± 17.9 pg·mL·h for consumption of the HFHC meal alone). However, no significant differences (change in AUC) were calculated for serum CRP and TNF-α. The findings of this pilot study suggest that consumption of lyophilized BRBs may attenuate postprandial inflammation in overweight or obese males consuming a HFHC meal. Further investigation of BRBs is warranted to better elucidate their inflammomodulatory potential.
• Martínez, M. E., Pond, E., Wertheim, B. C., Nodora, J. N., Jacobs, E. T., Bondy, M., Daneri-Navarro, A., Meza-Montenegro, M. M., Gutierrez-Millan, L. E., Brewster, A., Komenaka, I. K., & Thompson, P. (2013). Association between parity and obesity in Mexican and Mexican-American women: findings from the Ella binational breast cancer study. Journal of immigrant and minority health / Center for Minority Public Health, 15(2).
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  Obesity at diagnosis of breast cancer is associated with higher all-cause mortality and treatment-associated toxicities. We evaluated the association between parity and obesity in the Ella study, a population of Mexican and Mexican-American breast cancer patients with high parity. Obesity outcomes included body mass index (BMI) ≥30 kg/m(2), waist circumference (WC) ≥35 in (88 cm), and waist-to-hip-ratio (WHR) ≥0.85. Prevalence of obesity ([BMI] ≥ 30 kg/m(2)) was 38.9 %. For WC, the multivariate odds ratio (OR) (95 % confidence interval [CI]) for having WC ≥ 35 inches in women with ≥4 pregnancies relative to those with 1-2 pregnancies was 1.59 (1.01-2.47). Higher parity (≥4 pregnancies) was non-significantly associated with high BMI (OR = 1.10; 95 % CI 0.73-1.67). No positive association was observed for WHR. Our results suggest WC is independently associated with high parity in Hispanic women and may be an optimal target for post-partum weight loss interventions.
• Yousef, F. M., Jacobs, E. T., Kang, P. T., Hakim, I. A., Going, S., Yousef, J. M., Al-Raddadi, R. M., Kumosani, T. A., & Thomson, C. A. (2013). Vitamin D status and breast cancer in Saudi Arabian women: case-control study. The American journal of clinical nutrition, 98(1).
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  The role of vitamin D in breast cancer prevention is equivocal. Saudi Arabian women may be at greater risk of vitamin D deficiency because of a darker skin type and a greater likelihood of reduced ultraviolet B radiation exposure. Data regarding the vitamin D status of Saudi Arabian women and its relation to breast cancer risk are lacking.
• Martínez, M. E., Thompson, P., Messer, K., Ashbeck, E. L., Lieberman, D. A., Baron, J. A., Ahnen, D. J., Robertson, D. J., Jacobs, E. T., Greenberg, E. R., Cross, A. J., & Atkin, W. (2012). One-year risk for advanced colorectal neoplasia: U.S. versus U.K. risk-stratification guidelines. Annals of internal medicine, 157(12), 856-64.
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  Guidelines from the United Kingdom and the United States on risk stratification after polypectomy differ, as do recommended surveillance intervals.

Presentations

• Burgess, J. L., Fent, K., Grant, C., Solle, N., Jacobs, E. T., Jahnke, S., Griffin, S., Horn, G., Fahy, R., Morrison, P., Bertke, S., Jeong, K., Zhou, J., Littau, S., Jung, A., & Caban-Martinez, A. (2018, Summer). Design of and Data Collection in a National Multi-Site Fire Fighter Cancer Cohort Study. American Public Health Association. San Diego, CA.

Poster Presentations

• Thomson, C. A., Qui, L., Snetselaar, L., Kato, I., Shadyab, A. H., Jacobs, E. T., Crane, T. E., Kohler, L. N., Skiba, M., Thomson, C. A., Qui, L., Snetselaar, L., Kato, I., Shadyab, A. H., Jacobs, E. T., Crane, T. E., Kohler, L. N., & Skiba, M. (2019, Spring). The association between prebiotic fiber supplement use and colorectal cancer risk and mortality in the Women’s Health Initiative. ASPO.
• Bea, J. W., Crane, T. E., Jacobs, E. T., Thompson, P. A., Garcia, D. O., & Thomson, C. A. (2016, November). Abstract: Cruciferous vegetable intake is associated with changes in inflammatory biomarkers among breast cancer survivors in a physical activity program. American Institute for Cancer Research. Washington DC.
• Bea, J. W., Crane, T. E., Jacobs, E. T., Thompson, P., Garcia, D. O., & Thomson, C. A. (2016, Nov). Cruciferous vegetable intake is associated with changes in inflammatory biomarkers among breast cancer survivors in a physical activity program. American Institute for Cancer Research Annual Conference. North Bethesda, MD.
• Haenchen, S. D., Pottinger, H. L., Jacobs, E. T., Gast, P. B., & Ernst, K. C. (2013, March). Opinions of Arizona Physicians Regarding Childhood Immunizations. 2013 Public Health Research Poster Forum. Tucson, AZ: Mel & Enid Zuckerman College of Public Health.
• Sardo, C. L., Thomson, C. A., Hibler, E. A., Harris, R. B., Roe, D. R., Greenlee, H., Lance, M. P., Thompson, P., & Jacobs, E. T. (2013, November). Berry consumption and colorectal adenoma recurrence: a pooled analysis. American Institute for Cancer Research. Washington, DC.