Brown Cancer Center. Making tomorrow BRIGHTER for everyone.

 

Research Programs: Prevention and Control

Research Projects

Researcher, Ramesh Gupta, Ph.D. is co-pioneer of improvements in the technology for investigating the accumulation of DNA damage from carcinogenic substances--both environmental and naturally occurring--as it relates to mutations during DNA replication leading to malignancy. Several investigations are in progress which utilize this technology for earlier detection and prevention of cancer. more

Research by David Hein, Ph.D. in molecular epidemiology identifies individuals genetically susceptible to the development of cancer from environmental and occupational chemicals in order to focus treatment and prevention strategies on those at greatest risk.  more

Goals of the Cancer Prevention Program focus on the development of more effective means to reduce cancer morbidity and mortality. Emphasis is placed on educational and preventive interventions targeted to tobacco-related cancers. Specific goals include:

  • Identify and characterize cancer biomarkers (e.g., exposure, susceptibility, response) that enhance cancer risk assessment
  • Identify and address cancer-related public health needs in the Commonwealth of Kentucky and the greater Louisville region
  • Develop, implement, and test educational resources that reduce cancer risk and enhance access to effective early detection measures
  • Develop and implement innovative behavioral interventions for cancer prevention and care
  • Identify new cancer detection and prevention methods and translate these findings to clinical trials
  • Develop and implement methods and approaches to identify and reduce cancer-related health disparities
  • Develop and implement training programs in cancer prevention

Scientific Areas of Interest

Scientific areas of interest within the Cancer Prevention Program include behavioral oncology, biomarkers, genetics, and chemoprevention, and cancer epidemiology. These focus areas interact in many ways, especially via collaborations with the Kentucky Cancer Program. More specific information follows:

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Biomarkers, Genetics, and Chemoprevention.

Epidemiological and experimental data suggest that exposure to environmental carcinogens plays a substantial role in the causation of human cancers and thus are preventable. The majority of environmental carcinogens including aromatic amines, polycyclic aromatic hydrocarbons, heterocyclic amines, and cigarette smoke constituents need to be metabolized before they elicit biological responses. Electrophilic metabolites generated during bioactivation of toxicants interact with cellular macromolecules such as DNA and proteins, forming adducts. Endogenously formed reactive oxygen species and other electrophiles provide additional threat to the genome integrity. Efficient repair systems are operative in all living organisms to cope with such damage. However, if not repaired before the onset of DNA replication, or repaired erroneously, these DNA lesions can promote genetic alterations (e.g. mutations) that may be linked to an altered phenotype. If such alterations occur in growth-controlling genes, these mutations can lead to cell transformations and development of cancer. Therefore, progressive accumulation of both pre-mutational DNA lesions and genetic mutations are central to the disease process. The damage to macromolecules is generally accompanied with changes in activities and levels of the metabolizing enzymes, and genes associated with the bioactivation pathways and DNA repair processes are also modulated. Due to susceptibility differences (gene expression, genetic polymorphisms, DNA repair capacity), certain individuals may accumulate higher DNA damage, resulting in higher levels of gene mutations, and are at higher risk of developing cancer. These molecular events can be used as early biomarkers to investigate etiology of cancer development, as well as to identify efficacious agents to inhibit DNA damage and mutations, which may ultimately inhibit cancer development. Using cell-free, cell culture and animal models, and human-derived tissues/cells, various laboratories are defining the metabolic pathways involved in the disposition of carcinogens, monitoring DNA adduct formation and repair, and characterizing nature of metabolites and DNA adducts formed. Other laboratories are studying the effects of polymorphisms in genes for xenobiotic-metabolizing enzymes and DNA repair proteins to cancer risk. Still other laboratories are using burden of DNA adducts and protein adducts to define environmental exposure, as well as to understand the mechanisms of action of the toxicants. Modulation of gene expression and proteins by the emerging microarray and proteomics technologies, respectively in some other laboratories complement the other intermediate biomarkers. These studies thus encompass the many molecular events involved in the initiation and progression of cancer development, with emphasis on tobacco-related cancers.

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Biobehavioral Oncology

Behavioral oncology is integrated with other oncological sciences, making basic and applied behavioral science research available in the clinical context. They provide synergistic research and clinical programs that focus on biopsychosocial aspects of cancer control, from prevention and early detection through symptom management and palliative care. Their work involves basic science and translational research and clinical applications about how psychological, psychiatric, and social conditions impact the biology and behavior of cancer and the people who have cancer. They are clinically co-located in each multidisciplinary clinic in order to promote translational research, and provide direct and liaison service to cancer patients and other providers of cancer care.

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Cancer Epidemiology

The Kentucky Cancer Registry provides a statewide laboratory for epidemiological investigations. In 2000, the Kentucky Cancer Registry was selected as one of four expansion registries to become part of NCIs Surveillance Epidemiology and End Results (SEER) program. The SEER registries are considered to be among the most accurate and complete population-based cancer registries in the world and the funding from the SEER program has allowed the Kentucky Cancer Registry to further expand its quality control and gather complete follow-up information. The Kentucky Cancer Program (described below) maintains an established network providing ideal opportunities for population based research. Regional staff provide a link between the University and the community, providing researchers an opportunity to easily access study participants from across the state. Ongoing epidemiological studies include the Western Louisville metropolitan area with a higher percentage of African American residents and environmental health issues related to presence of a large chemical manufacturing base, and Paducah Kentucky which is the site of a uranium gaseous diffusion plant. Much of the research has been "molecular epidemiology" that incorporates exposure and genetic susceptibility biomarkers into cancer risk assessments. Increasingly, the cancer epidemiology research also incorporates behavioral measures.

Population-based epidemiology studies are expanding rapidly. For example, Dr. Richard Baumgartner is Principal Investigator of the New Mexico Health, Eating, Activity and Lifestyle (HEAL) Study now entering its 10th year of follow-up. HEAL is a multi-centered investigation of the influence of body weight, composition, diet, physical activity, and hormones on prognosis among female cases of breast cancer ascertained by the SEER cancer registries in New Mexico, Western Washington, and Los Angeles. This effort is unique among SEER Special Studies for the depth and complexity of the information collected, and provides important information on modifiable behaviors that may improve prognosis in breast cancer survivors. Dr. Kathy Baumgartner is Principal Investigator of the 4-Corners Women's Health Study (4-CWHS), a case-control study conducted in collaboration with the University of Arizona, Colorado, and Utah. The aim of the 4-CWHS is to explore the contradiction between breast cancer incidence rates and prevalence of exposures among the primary ethnic groups in the Southwest. The focus is on the relationship between breast cancer and obesity and associated indicators of insulin status. The roles of genetic susceptibility and metabolic and lifestyle exposures are being investigated within the context of this study, and genetic admixture is being used to define the continuum of ethnic diversity in the population. The inclusion of three diverse populations enhance ability to detect relevant genetic associations. She is also the Principal Investigator of a new study, Ethnicity, Breast Cancer Recurrence & Long-Term Quality of Life, focused on breast cancer recurrence, survival and long-term quality of life among women who previously participated in a case-control study. A primary interest of this study is to determine ethnic differences in prognosis and quality of life. This follow-up study will provide a unique opportunity to evaluate factors influencing survival and recurrence in long-term breast cancer survivors, and quality of life compared to population-based controls. Importantly, it will investigate the interaction of ethnicity with other prognostic factors in an aging cohort. These studies have important implications for treatment of women and long-term care of breast cancer survivors and are excellent models for cancer epidemiology research that will be developed in Kentucky making use of the combined resources of the Kentucky Cancer Registry, Kentucky Cancer Program, Department of Epidemiology, the Cancer Prevention Program, and other resources in the Brown Cancer Center.

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Kentucky Cancer Program (KCP)

The Kentucky General Assembly established a state mandated, cancer control program within the structure of the Brown Cancer Center over 25 years ago. Jointly administered by the states two major universities, the Kentucky Cancer Program (KCP) has 12 regional offices staffed by cancer control specialists who serve as catalysts for education, service, and research programs within their respective communities. Serving over 100,000 residents each year, KCP has become a national model and a state leader in cancer control. Grounded in an academic environment, programs are science based, data driven, and evaluated, yet guided by the community. Outreach activities span the continuum of disease addressing the states top cancer problems. Cancer control specialists mobilize communities to act on local problems by spearheading coalitions and working in collaboration with partners.

Reaching Kentuckys diverse populations including African Americans and Hispanics in urban and rural regions, Appalachians, farm families, as well as the states historically low literate, undeserved, and uninsured groups is a priority. Programs are customized to meet the cultural and language needs of these individuals who frequently experience cancer health disparities.

The Kentucky General Assembly allocates approximately $1 million dollars annually to the Brown Cancer Center for community outreach. An additional $500,000 is awarded each year from other sources including the Centers for Disease Control and Prevention, the Kentucky Department for Public Health, and the Susan G. Komen Breast Cancer Foundation.

Education, particularly related to cancer prevention and early detection, has become an important service to public and professional audiences in Kentucky. Cancer control specialists explain medical research, providing a bridge between scientific breakthroughs and public understanding.

Cancer control specialists link Brown Cancer Center faculty to research participants, as well as conduct behavioral research that will improve cancer prevention and early detection programs.

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Selected ongoing research interests in the Cancer Prevention Program

  • Gene-environmental interactions in cancer risk and etiology
  • Functional genomics of carcinogen metabolizing enzymes
  • Role of DNA adducts from environmental carcinogens and endogenous compounds in cancer development
  • Mechanisms for interindividual variability in metabolism of environmental carcinogens and DNA repair
  • Mechanisms of carcinogen-induced mutagenesis and DNA repair
  • Regulation of cell cycle and cross signaling between cell cycle regulation and DNA repair
  • Regulation of carcinogen metabolizing enzymes
  • DNA-, protein- and serum-based intermediate biomarkers and their association with pathogenesis of cancer
  • Gene expression-based screening for assessment of risk of human cancers
  • Mechanisms by which estrogens regulate physiological functions in different cancer cell types, including breast and endometrial cancer cells, and lung adenocarcinoma cells
  • Identification and characterization of efficacious chemopreventive agents and their translation to chemopreventive intervention in clinical trials
  • Religiosity and cortisol rhythm in women with cancer
  • Spiritual expression and immune status in women with metastatic breast cancer
  • Knowledge, attitudes and clinical practices involving tobacco cessation among health care professionals
  • Health care disparities in cancer screening, etiology and prevention
  • Predictors of smoking initiation and smoking patterns among college students
  • Effects of life stress (trauma, socioeconomic status, early experience) on cancer patient quality of life and functional status
  • Quality of life, palliative care, and end of life care in cancer patients
  • Effects of psychosocial factors (depression, social support, coping mechanisms, personality) on cancer patient quality of life as well as recurrence and survival
  • Effects of health behavior (sleep, physical activity, diet) on cancer patient quality of life and functional status
  • Biological mediators of psychosocial effects on cancer outcomes, including neuroendocrine (glucocorticoids, catecholamines), immune (cellular and humoral responses), and inflammatory (TNF-alpha, IL-6, and CRP)
  • Behavioral, cognitive, and affective sequelae of cancer screening
  • Adjuvant treatment decision-making
  • Evaluation of programs to promote cancer screening among health care providers
  • Community application of HPV self-test for cervix cancer screening
  • Etiology and epidemiology of childhood acute lymphoblastic leukemia
  • Chemoprevention of liver cancer using Chinese herbal medicines
  • Legal, ethical, and policy issues regarding genetics, race and health care disparities
  • Cancer effects from long-term radiation exposures
  • Structural biology and functional genomics of cannabinoid receptors
  • Effects of tobacco exposure during pregnancy
  • Effects of obesity, weight change, physical activity, and body composition on cancer risk
  • Effects of diet in cancer initiation and prevention
  • Effects of tamoxifen or hormone replacement therapy on lung adenocarcinoma
  • Risk versus benefits of smokeless tobacco in patients in which other smoking cessation measures fail
  • Roles of diet, physical activity, and body weight in breast cancer risk and prognosis
  • Hormonal, molecular and genetic biomarkers for breast cancer risk and prognosis
  • Ethnic disparities in breast cancer risk and prognosis
  • Quality of life in long-term breast cancer survivors

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Program Head

Researcher(s)

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