Cancer

Analyses to evaluate how COVID-19 severity effects the outcomes of melanoma patients on active anti-cancer treatment. Co-PI: Amanda K Arrington, MD MHM FACS FSSO

Chronic diseases can be caused by a multitude of factors including numerous environmental exposures. To better understand how exposures to mixed contaminants in water may relate to gastric cancer rates, we exposed gastric organoids to a mixed matrix of contaminants to quantify how targeted health outcomes change with exposure scenarios. Preliminary results indicate increased H. pylori  infection and cancer markers with increased arsenic concentrations. Results are important for identifying at risk communities and preventing gastric cancers. This project was funded by the University of Arizona. 

Stomach cancer is the third leading cause of cancer death globally. Rates for stomach cancer are 3-4 times higher among the Navajo Nation compared to the non-Hispanic white population in Arizona. Helicobacter pylori (H. pylori) plays a role in the healthy human gut, but it is also associated with multiple chronic diseases, including stomach cancer. A multi-year research program, conducted in partnership with Northern Arizona University through the Partnership for Native American Cancer Prevention, seeks to estimate the prevalence of H. pylori among Native Americans. The study in 2018 reported a 56.4% prevalence of H. pylori within participants from three Navajo chapters, with 72% of households having at least one infected person. This research program was expanded to continue the study through other regions of Navajo Nation. Together these studies will test hypotheses that the high H. pylori prevalence in Navajo communities correlates with environmental and behavioral factors as well as diagnostic delays and to determine the genotypes of H. pylori in Native Americans in Northern Arizona and antibiotic resistance to therapies.

The purpose of this project is to investigate the association between infertility and risk of postmenopausal breast cancer among women in the Women’s Health Initiative. This project was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. 

Women firefighters have high rates of post-traumatic stress disorder, increases in certain cancers, and adverse reproductive outcomes compared to women in the general population. However, the lack of sufficient information on the causes of and mechanisms leading to these occupationally related illnesses limits the creation of effective interventions. The goal of this project is to evaluate stress, cancer risk, and reproductive toxicity in women firefighters and to develop, beta test, and assess the feasibility of a peer support intervention. This project was funded by the Federal Emergency Management Agency. 

Patient navigation programs can serve as a key approach to achieving the triple aim in cancer care by improving patient experience, improving population health, and reducing health care costs. The goal of this project is to develop a model which can be used by various cancer centers to predict costs and outcomes involved in implementing and managing a patient navigation program. Model variables will be derived from literature review and various scenarios will be built into the model for screening, diagnosis, survivorship, and end of life care. Outcome projections from the model can be used to develop a business case for implementing patient navigation programs. Dr. Prashanthinie Mohan is also a collaborator on this project. 

The objective of this project is to develop a dietary intervention to improve self-management of bowel dysfunction in patients with ostomies or anastomosis. This project received funding from the National Cancer Institute. 

This research will establish prevalence data of nonalcoholic fatty liver disease (NAFLD) and the frequency of a specific indicator of genetic risk, the PNPLA3 allele, in Tucson, AZ. This project will accomplish this by assessing relationships between the PNPLA3 genotype, liver fat, and dietary behaviors in Mexican-origin adults, and evaluating the knowledge, attitudes, and beliefs of NAFLD risk, including genetic risk, held by Mexican-origin men and women. This project is funded by the American Cancer Society through its Institutional Cancer Research Center Grant. 

Colorectal cancer is one of the most common malignancies in the United States. There is an increasing number of studies using recurrent colorectal adenomas to evaluate the prevention effect for some promising agents. The number of recurrent colorectal adenomas is often measured by performing colonoscopy, which is known to miss a small percentage of existing adenomas and result in misclassification on recurrence status. In addition, some participants might not comply with the schedule of follow-up colonoscopy, which is scheduled to be performed once at the end of the study and, therefore, have variable follow-up lengths compared to the compliant participants. The reasons that a participant cannot comply with the schedule of follow-up colonoscopy could be informative of the risk of recurrence and then bias the results derived from statistical methods that do not adjust for noncompliance. Conventional statistical methods for colorectal adenoma prevention trials cannot simultaneously incorporate misclassification and variable follow-up into analysis and cannot adjust for informative non-compliance without strong assumptions and, furthermore, may incorrectly produce equivocal results for some promising nutritional or chemopreventive agents. The purpose of this application was to develop sophisticated and appropriate statistical models to describe the relationship between the preventive agents and recurrence of colorectal adenomas. We used a latent variable recurrence model, which assumed a portion of non-recurrent participants were misclassified due missing existing adenomas at follow-up colonoscopy, to handle misclassification and a weight function to incorporate the length of follow-up into analysis. The prognostic factors for risk of recurrence was incorporated into the weight function to adjust for potential informative non-compliance. The hope was that a  better understanding of the relationship between preventive agents and recurrence of colorectal adenomas would allow clinical investigators to identify an agent that truly reduces recurrence of colorectal adenomas. This project was funded through a grant from the National Cancer Institute. 

This application, entitled “Student Transformative Experiences to Progress Underrepresented Professionals” (STEP-UP) for cancer prevention, is a multidisciplinary initiative led by the Cancer Prevention and Control and Health Disparities Programs’ faculty at the University of Arizona Comprehensive Cancer Center. It is uniquely designed to provide 55 undergraduate and 54 Masters’ degree seeking students with an intensive, 12-week summer research experience in cancer prevention and control. Educational pedagogy will inform on our methodology in order to assure students receive the quality research experience that not only will increase understanding, but also will motivate students toward a continued educational commitment to advance in cancer prevention and control sciences. The emphasis in training will be largely within the clinical trials to community-based participatory research end of translational research, yet offering students 2 week-long immersion opportunities to experience cancer prevention and control science across the entire continuum of basic to applied and even dissemination research. Over 35 faculty members from diverse disciplines who are funded in cancer prevention and control research are committed to this program. The program fills a gap in our web of training opportunities for underrepresented students and yet builds on a substantial foundation of purpose-driven efforts at the UA and the Arizona Cancer Center to attract and retain a diverse student body in cancer prevention and control research. Importantly, this effort leverages our international reputation in cancer prevention research. Our specific aims include: 1. Recruit undergraduate and Master’s level graduate students from URM into the STEP-UP in cancer prevention 12-week summer experiential cancer prevention and control research training; 2. Provide an integrated, innovative, multidisciplinary educational experience in cancer prevention and control research that strengthens self-efficacy and intrinsic motivation to become a cancer prevention and control scientist; 3. Support mentoring and professional relationships with scientists, research programs and community partners; 4. Conduct formative and summative evaluations to improve the program over time. The training program is centralized in Southern Arizona and offers experiential learning within our unique catchment area which is rich in diversity relative to ethnicity (30.7% Hispanic), race (5.8% Native Americans) and age (16.4% over age 65 years). This distinctive location, strong community ties, university facilities and resources for research and education, as well as committed and experienced faculty mentors and program leaders, assures a quality program that will impact the diversity, competence and commitment of the cancer prevention and control workforce of the future.

The purpose of this project is to develop and test a framework for establishing a long-term firefighter multicenter prospective cohort study focused on carcinogenic exposures and effects.  The specific aims are to: 1) Establish an oversight and planning board to provide study oversight, foster communication among fire organizations and help develop a long-term funding plan; 2) Create and test a cohort study data coordinating center and harmonized survey data protocols; 3) Develop and evaluate an exposure tracking system paired with quantitative exposure data to construct a firefighter carcinogen exposure matrix; and 4) Create a biomarker analysis center and evaluate the association between cumulative firefighter exposures and epigenetic effects. Relevance: Cancer is a leading cause of fire service morbidity and mortality, and a recent National Institute for Occupational Safety and Health (NIOSH) study demonstrated an excess mortality rate for cancer in firefighters compared with the general population (Daniels et al., 2014).  Firefighters are exposed to multiple carcinogens in the workplace through skin contamination and inhalation.  However, we currently do not understand which individual exposures are responsible for cancer in firefighters, the mechanisms by which these exposures cause cancer, or effective means of reducing exposures.  Since cancer has a long latency period, biomarkers are also needed that can measure the effects of carcinogen exposure well before the development of cancer, when interventions to prevent disease could be effective.  Development of a large (>10,000 firefighter) multicenter firefighter cancer prospective cohort study will address these needs, but the framework for such a study needs to be first developed and tested among a smaller initial set of fire service partners.  Methods: The study will build on recent and developing firefighter cancer prevention studies in Arizona, Florida and Massachusetts, adding volunteer and combination fire departments.  1) An Oversight and Planning Board will be established by the Fire Protection Research Foundation (FPRF) in association with the National Fallen Firefighter Foundation (NFFF) Fire Service Occupational Cancer Alliance (FSOCA) to provide oversight of the study through collaboration among fire service organizations, academia, and government agencies, and develop a long-term funding and sustainability plan.  2) A Data Coordination Center will design, develop and evaluate a framework for a multicenter prospective cohort study of firefighters and cancer risk, including standardized participant survey data collection tools and analysis protocols sufficient to address the short- and long-term study objectives as well as linkage with long-term outcome data including cancer development.  3) An Exposure Assessment Center will develop a carcinogen exposure matrix using information gleaned from self-reported and quantitative exposure measurements to provide improved occupational exposure data for comparison with epigenetic outcomes and eventual cancer outcomes.  Carcinogen exposures associated with specific fire types and job tasks will be evaluated across fire departments through exhaled breath monitoring and analysis of urine for absorbed contaminants, providing information to guide exposure reduction strategies.  4) The Biomarker Analysis Center will carry out pilot studies of epigenetic markers of cancer effect and cancer risk comparing firefighters with a range of cumulative exposures and non-firefighter controls.  For these purposes, blood and buccal cells will be collected during annual medical surveillance evaluations.  Anticipated outcomes: The proposed research will: establish the framework necessary for the subsequent development of a large multicenter cohort study of cancer in the fire service; advance our understanding of firefighter exposures to carcinogens; and help identify biomarkers of carcinogen effect and cancer risk.

Purpose and Aims: The purpose of the proposed research is to identify effective methods of reducing firefighter exposure to carcinogens and associated toxic effects through completion of the following specific aims: 1) Evaluate exposure to carcinogens throughout the work shift; 2) Measure biomarkers of carcinogenic effect in relation to workplace exposures; and 3) Within a risk management framework, test the effectiveness of interventions to reduce fire service carcinogen exposure and effects. Relevance: Cancer is a leading cause of fire service morbidity and mortality.  Exposure to carcinogens occurs through skin contamination, through the lungs when respiratory protection is not worn during all phases of fire suppression and overhaul, and through inhalation during standby, operation of apparatus and off-gassing of equipment.  In addition to fire smoke, diesel exhaust exposure can occur from operation of apparatus at the fire ground and in the station.  Since cancer has a long latency period between exposure and disease onset, measurements are needed that can determine the effectiveness of new interventions on a much shorter time interval.  Methods: Exposure to particulates and volatile chemicals will be measured at the fireground and in-transit.  Diesel particulate matter monitoring during responses and in the fire station will also be completed.  Blood and urine collected during annual medical surveillance evaluations and post-fireground activities will be analyzed for chemical contaminants.  Biomarkers of carcinogenic effect will also be analyzed pre- and post-exposure, and evaluated for association with measured chemical contaminants.  The extent to which firefighter chemical exposures and biomarkers of effect can be reduced by following risk management steps will be determined.  Anticipated outcomes: The proposed research will identify carcinogenic exposures throughout the fire shift and measure the effectiveness of interventions designed to reduce cancer risks. 

In the U.S., Hispanic males have the highest rate of overweight and obesity when compared to males of other racial/ethnic groups. Obesity contributes to the risk for certain cancers in Hispanics. For example, obesity is associated with non-alcoholic fatty liver disease (NAFLD), which is 1.4 and 1.9 times more common in Hispanics than in Non-Hispanic Whites (NHW) and African Americans, respectively. While not all individuals with NAFLD develop liver complications, nearly 30% will develop nonalcoholic steatohepatitis (NASH) and be at risk for hepatocellular carcinoma, the most common form of liver cancer in adults. Consequently, Hispanic males have the highest rates of liver cancer incidence in the U.S., twice those of NHW men. Weight loss is considered the first line of prevention for NAFLD progression. Yet, current research is lacking to inform best practices to engage Hispanic males in weight loss and/or to promote a successful weight loss trajectory. Without this information, the health disparities associated with obesity related cancer will continue to increase. Using existing practice guidelines and evidence from our qualitative assessments in overweight/obese Hispanic males, we will test a novel intervention approach to address this knowledge gap. We propose to 1) assess the feasibility, acceptability and preliminary efficacy of a gender- and culturally-sensitive weight loss intervention in 20 overweight/obese Hispanic males ages 18-64 over 24 weeks; and 2) examine pathologic changes in the liver (NAFLD, NASH, fibrosis, or cirrhosis) in 20 overweight/obese Hispanic males ages 18-64 over 24 weeks using a non-invasive Magnetic Resonance Imaging (MRI) of the liver. This project will be the first gender and culturally-sensitive weight loss intervention of which we are aware to explicitly target Hispanic males with an emphasis on reducing body weight. In addition, the intervention will provide highly impactful formative research on the effects of a weight loss lifestyle intervention on liver histology. Given the Hispanic population is the fastest growing in the U.S., efforts to identify strategies to promote weight control among Hispanic males has potential to significantly impact obesity-related cancer health disparities.

Located in the Mel and Enid Zuckerman College of Public Health at the University of Arizona and funded by the state tax on tobacco products, The Arizona Smokers’ Helpline (ASHLine) is one of over 50 quitlines across the United States. Established in 1995, it is also one of the oldest and most seasoned quit lines in existence.  As a member of the North American Quitline Consortium, ASHLine is actively engaged in collaborations, research, evaluation and quality improvement to assure all Arizonans have access to high quality, evidence-based tobacco cessation services and support. Nationally, quit rates reported among North American quit lines vary, averaging around 30%.  The Arizona Smokers’ Helpline (ASHLine) has been helping people quit tobacco since its inception in 1995. We are a comprehensive quitline, offering free telephone (both reactive and proactive) and web-based quit services and four to twelve weeks Nicotine Replacement Therapy (NRT). In addition, we have fax and electronic provider referral program and provide free training and technical assistance to healthcare providers and community partners statewide. The Arizona Smokers’ Helpline (ASHLine) is a service entity well-positioned to contribute to ongoing tobacco control efforts by providing effective, evidence-based support to individuals in their effort to end tobacco use.

To date, no prospective, randomized, placebo-controlled clinical trials have been conducted to test the hypothesis that exposure to diindolylmethane (DIM), in combination with tamoxifen (TAM), can significantly modify breast cancer risk. The DIME Study tests the novel hypothesis that DIM will demonstrate an enhanced efficacy of TAM by modulating the breast parenchyma to a ‘low’ density, ‘low risk’ state and alternatively by favorably modulating steroid hormone metabolism. In fact, DIM has been shown to act on breast cancer risk through a variety of mechanisms, and as such, core breast biopsy tissue samples and blood for alternate hypotheses testing (e.g., COX-2, prolactin receptor, proliferation assays, AhR, inflammatory markers, oxidative stress, etc) are collected in the context of this trial. The recruitment portion of the study ended in September 2015. Study results will be available as of late 2016. This study was funded by the National Cancer Institute. 

Ovarian cancer accounts for over 18,000 deaths each year in the U.S. with disease progression rates estimated at 60-70% after 4 years. The efficacy of a physical activity + dietary intervention to increase progression-free survival (PFS) in this vulnerable population is currently being tested in a hypothesis-driven, randomized, attention-control study of 1070 women with prior invasive disease [(Gynecological Oncology Group (GOG) 0225 study (Lifestyle Intervention for oVarian cancer Enhanced Survival- (LIVES) Trial]. Here, we propose to take advantage of the trial infrastructure and capacity to collect repeat blood samples to evaluate the mechanistic underpinnings that might explain any changes in health indices by treatment arm over time. The overarching hypothesis is that change in metabolic and inflammatory status of participants, that is expected to demonstrate a reduction in inflammation and metabolic deregulation in the intervention group participants more so than the attention-control group, will be associated with increased PFS. A secondary focus of the proposed work will be the interaction with central adiposity. The Specific Aims include: To determine if the LIVES intervention alters biomarkers of metabolic deregulation in women previously treated for stage II-IV ovarian cancer; Aim 2: To determine if any effect of the intervention on biomarkers is mediated by change in central adiposity; and Aim 3: To determine if any effect of the intervention on biomarkers is modified by baseline central adiposity including exploration of central adiposity using Computerized Tomography (CT) scans. Our longer term goal is to determine whether change in central adiposity, insulin/lipid metabolism or inflammation is associated with progression free survival.

“Chemo-brain”, self-reported cognitive impairment following chemotherapy, is a common complaint among cancer patients and survivors. This study compared a web-based brain-training program to usual care to improve cognitive functioning. Participants were randomly allocated to brain-training or usual care, and followed up post-intervention and 6 months later. We also assessed other important patient-reported outcomes, including fatigue, quality of life, stress, and anxiety. Funding for this project came from the Cancer Council NSW in Australia and the University of Sydney. 

R25T Cancer Prevention and Control Training Grant. More information about this program and associated funding can be found here: https://cancercenter.arizona.edu/researchers/research-programs/cancer-prevention-control

Abstract not available. 

 A needs assessment of the potential for under-reporting of melanoma in Arizona and to identify the barriers to appropriate reporting. This assessment was done working with community Melanoma Task Force. This project was funded by the Centers for Disease Control and Prevention under the United States Department of Health and Human Services. 

The study started in 1993 to evaluate health outcomes in aging postmenopausal women and to identify factors associated with healthy aging. Between 1993 and 1998, more than 161,000 women between 50 and 79 years of age joined the WHI. Beginning in October 2004, participants were consented for sequential 5-year WHI Extension Studies (ES). The research team continues to collect self-reported as well as medical record adjudicated health and mortality data. A team of junior investigators are engaged with data analysis in an effort to advance the dissemination of WHI research findings. Arizona research team members have published over 45 manuscripts in the past 8 years using this well-characterized and robust phenotypic information.

Melanoma is a public health concern since the incidence is increasing faster than any other cancer in the United States. While ultraviolet radiation is a widely accepted risk factor for this disease, understanding the possible role arsenic exposure may play in the development of melanoma will allow for a more developed base of knowledge regarding the etiology of melanoma.We will conduct a population-based case-control study of incident cutaneous melanoma (CM) cases and arsenic content detected in toenail samples. To eliminate biases, we will a) use newly diagnosed cases rather than prevalent cases, b) use toenails collected within 1-9 months of diagnosis, c) use a non-cancer control group, and d) use neutron activation analysis (NAA), considered the gold standard in trace element analyses. CM cases in Iowa residents will be semi-rapid reported through the Iowa Cancer Registry. Population-based controls will be identified using the Iowa Voter Registration file, which is comparable to the Iowa Census data. We will mail subjects an introductory letter, instructions for the toenail sample collection and small baggie. We will then conduct the survey using computer-assisted telephone interviewing (CATI) software in order to collect complex data related to residential histories (water source, sun exposure, and occupations). This format will allow interviewers to collect a residential history and probe for additional information about potential exposures at each residence. We will focus on arsenic detected by NAA in toenail samples from cases and controls. Additionally, we will assess known risk factors for CM in this population, including natural and artificial UV exposure, residential and occupational histories, sun sensitivity factors, family history of skin cancer, and sunscreen use. We will also correlate available data on arsenic levels in current drinking water to arsenic in subjects' toenails. Recording residential histories and relating them to current and historical water sources will allow us to examine the length of the potential arsenic exposure, since drinking water is believed to be the main source of arsenic exposure and may provide evidence of long-term exposure. Collecting biomarkers of arsenic exposure along with surveying subjects about known UV factors and their sun sensitivity will allow for the examination of important interactions and potential confounding of the association between arsenic and CM. This knowledge will in turn help identify a group of high-risk individuals for public health messages to target. Funding for this project comes from the National Institutes of Health. 

This project was designed to investigate the role of vitamin D and genetic differences in the Vitamin D pathway on the develop of the precursor to colon cancer. The research team is using combined approaches from epidemiology and molecular biology to study functional changes and the pathway and their effects on colorectal carcinogenesis. Project funding came from the National Cancer Institute.