Jennifer Davis, Ph.D.
Nearly 40% of US adults are at increased risk of developing colorectal cancer due to obesity. Further, tumors arising in the context of obesity may have distinct biology, requiring specific prevention strategies. Our research uses a mouse model of colorectal cancer to understand the biological differences of tumors arising in lean compared to obese animals. After comparing tumor biology, we plan to use this model to evaluate prevention strategies in these contexts. Identifying an effective prevention strategy may greatly reduce the colorectal cancer risk for adults battling obesity.
Maro Ohanian, D.O.
Toxic metal contamination of our food and water receives very little attention from the medical community, despite worsening globally. Once stored in the bones, metals damage the bone marrow, cause DNA damage, and have been associated with acute myeloid leukemia (AML). Metals can be detoxified from the body by a process called “chelation,” using FDA-approved medications that are inexpensive, and have a long history of safety and efficacy in removing metals from the body. We will study metal detoxification as prevention strategy for AML by combining metal detoxification with standard treatment in patients with myelodysplastic syndrome, which is the precursor of AML. Understanding the role of metals in the development of AML may identify critical biochemical steps or gene-environmental interactions that impact cancer risk, treatment responses, and offer insight on cancer prevention and treatment.
Isabelle Bedrosian, M.D.
Unlike advances made in breast cancer treatment, progress in prevention has been far more limited. A key reason for advances in breast cancer treatment has been the understanding that breast cancer constitutes not one but several diseases. Strategies for breast cancer prevention have failed to consider this heterogeneity and little is known about the molecular changes that occur during the development of the different types of breast cancer. This therefore limits the ability to develop prevention strategies that are relevant to all the subtypes of the disease. The goal of our research has been to define the molecular map of the precancerous state by subtype in order to identify subtype relevant opportunities for targeted prevention. Because of its more aggressive biology and lack of drugs for prevention, we have focused on the triple negative breast cancer subtype. Using a triple negative breast cancer progression model that represents a spectrum ranging from normal, pre-cancer and cancer, we have identified a number of molecular changes that are key drivers of the disease specifically early transition from normal to precancer This proposal focuses on targeting some of these molecular aberrations that occur during normal to precancer stages in the development of triple negative breast cancer to develop innovative approaches to prevent cancer early on when treatments are more likely to be successful. To quickly benefit the high-risk patients, one of the strategies we will test includes repurposing a safe drug (statin, an FDA approved cholesterol lowering drug) that targets a pathway we have identified as relevant to the early precancerous steps in the development of triple negative breast cancer. The results of this proposal if successful will serve as the basis of developing clinical trials of novel targeted agents for prevention of triple negative breast cancer in at risk women.
Xiangwei Wu, Ph.D.
p53 is a crucial tumor suppressor that stops tumor development in most species and is the most frequently inactivated gene in human cancers. Although about 50% of cancer patients harbor mutant p53, many tumors at early stages of tumor development retain wild type p53. The presence of wild-type p53 in cancer precursor lesions presents an opportunity for chemoprevention by activating p53 to suppress tumor progression. The MDM2 protein is a key negative regulator of p53 and plays a primary role in antagonizing p53 through direct interaction. Small molecule MDM2 inhibitors that block the MDM2–p53 protein–protein interaction would liberate p53 from MDM2, thereby restoring the tumor suppressor function of wild-type p53. We hypothesize that enhancement of wild-type p53 functions by blocking MDM2-p53 interaction in precursor lesions using MDM2 inhibitor is an effective approach for cancer prevention. We will test this hypothesis in mouse model pancreatic cancer. If successful, our study will pave a new way for pancreatic cancer chemoprevention.
Grace Smith, M.D., Ph.D.
For cancer patients, the financial burden of cancer treatment is comprised of many dimensions—not just direct out-of-pocket costs, but also subsequent debt, medical bankruptcy, and disrupted employment—and this phenomenon is now recognized as the “financial toxicity” of cancer treatment.
Younger, working-aged patients, women, and medically underserved cancer patients are at especially high risk for financial toxicity. For working-age cancer survivors, disrupted employment, especially unwanted unemployment, is one of the most impactful and long-lasting consequences of financial toxicity, lasting even years after cancer treatment and cure.
Though we know disrupted employment occurs in as many as 30% to 50% of cancer survivors, we know very little about of what factors predict employment outcomes after treatment, and more importantly, what are the most intervenable factors that can help improve this cancer survivorship toxicity.
Our research uses a patient-centered approach to characterize, from a survivor perspective, the risk factors that worsen—and the mitigating factors that improve—resilience and recovery from adverse employment outcomes occurring over the cancer survivorship trajectory.
Is fatigue during cancer survivorship a result of reduced cellular energy? Investigating mitochondrial functioning in relation to fatigue
Elisabeth Vichaya, Ph.D.
Fatigue is one of the most common and distressing symptoms experienced by cancer survivors. Unfortunately, the mechanisms underlying its development and persistence are poorly understood. Based on newly emerging data, we propose to study the role of mitochondrial dysfunction in the persistence of fatigue in breast cancer survivors. Disruption of mitochondrial function caused by cancer and cancer treatment may result in a chronic reduction in cellular energy production capacity that may lead to the experience of fatigue.
Susan Peterson, Ph.D., M.P.H.
This project will test the feasibility of using the Texas Cancer Registry (TCR) to identify the prevalence of genetic testing for BRCA1/2 gene mutations in cancer survivors of triple-negative breast cancer (TNBC) or high-grade serous ovarian cancer (HGSOC), and their at-risk relatives. We also will determine awareness and access to genetic counseling and testing services among patients who have not had counseling and testing, as well as awareness and access to risk management options for mutation-positive patients. Finally, we will assess the feasibility of utilizing a patient navigation approach to facilitate access to BRCA education, genetic counseling, genetic testing, and risk management options (for mutation-positive patients).
Tina Shih, Ph.D.
The purpose of this project, entitled “Capacity Constraints for Lung Cancer Screening Facilities in Providing Smoking Cessation” is to understand whether the current healthcare system has sufficient capacity to deliver lung cancer screening for individuals at high risk for lung cancer. We are especially interested in understanding the availability of lung cancer screening facilities in geographic areas with a higher proportion of residents who are smokers. If a shortage of screening facilities were identified in certain geographic areas, we will further explore the contributing factors. In addition, we will study factors facilitating and hindering the delivery of smoking cessation interventions in lung cancer
screening facilities. We will conduct this project using a combination of quantitative and qualitative research methods. The project team includes faculty at MD Anderson with expertise in economics, implementation science, tobacco cessation research, and survey methodology. Finding from this research will help policy makers identifying geographic areas with greatest need for public health effort to improve its capacity in delivering lung cancer screening.
Grace Smith, M.D., Ph.D.
We are creating the Texas Community Feedback Survey: CAncer Patients In TexAs (CAPITA) to understand the needs and experiences of cancer patients and survivors across Texas. Understanding “patient-reported outcomes (PROs)” is a critical need, in order to inform the design of treatments and survivorship plans in a way that will be meaningful to patients—that is, patient-centered. Therefore, our research team is partnering with the Texas Cancer Registry to establish an approach to regularly survey and communicate
with diverse cancer patients across Texas, to understand their needs for information and quality of life support resources.
Jason Robinson, Ph.D.
Working memory refers to a brain process that enables us to simultaneously manipulate multiple pieces of information and control our behavior. Previous research has shown that poor working memory is associated with relapse in smokers who are trying to quit. In this study, we will test whether two weeks of in-home, computerized cognitive training is capable of improving working memory capacity in smokers. If we find that cognitive training improves working memory capacity, we will conduct future studies in which we will assess the efficacy of cognitive training as an adjunct to standard smoking-cessation interventions. In the long run, it may be possible to improve smoking-cessation rates through the use of easily-administered, cost-effective cognitive training.
Qiang Shen, M.D., Ph.D.
Currently available drugs for breast cancer prevention can only prevent a portion of ER-positive breast cancer. Effective preventive therapies are therefore urgently needed for the unpreventable/resistant ER-positive and all ER-negative breast cancers. In this regard, we have developed a new class of anti-cancer agents including HJC0152 that target and reprogram glucose metabolism and energy production. HJC0152 has demonstrated significant effects on reducing ER-negative breast cancer development in animal models by inhibiting pre-cancerous changes, making it a promising chemoprevention drug candidate for future breast cancer prevention.
Kyle R. Noll, Ph.D.
Glioma is a type of brain cancer with poor prognosis. Early detection and surgery to remove as much of the tumoras possible is critical to optimizing the quality-of-life of glioma patients. However, this type of surgery carries the risk ofdamaging normal regions of the brain that control critical functions like speech and language. To minimize these risks,direct cortical stimulation (DCS) is used during glioma surgery to localize those regions of the brain responsible forlanguage and thus guide surgery. However, this method remains largely unstandardized and has various limitations. Thisproject addresses some of these limitations and seeks to improve the intraoperative mapping of particular brain functionsrelated to speech and language in order to maximize the amount of patient language functioning that is preserved.
Identification of cardiac toxicity risk based on cardiac dose volume relationships among patients treated with IMRT for Hodgkin lymphoma across the treatment eras
Chelsea Pinnix, M.D., Ph.D.
Combined modality therapy with doxorubicin-based chemotherapy followed by consolidative radiation therapy (RT)to the mediastinum is the standard of care for limited-stage Hodgkin lymphoma (HL). Cure rates are excellent; however,many survivors face long-term effects of the therapy which are associated with considerable morbidity and, in somecases, mortality. The specific cardiac RT doses that predispose to long-term toxicity are largely unknown. This studyseeks to identify threshold RT doses and characterize dose-volume relationships to various cardiac structures that resultin increased risk of late cardiac toxicity among a large cohort of patients treated for HL. This work represents the firststudy to correlate RT-induced cardiac toxicity with actual doses delivered to cardiac structures based on individual patientCT scans at the time of RT delivery. These data have enormous potential to significantly contribute to new RT doseconstraintguidelines for lymphoma patients that will be treated with mediastinal RT.
Dimpy Shah, Ph.D.
Bone marrow transplant is an important treatment option for many blood cancers; however, long-lasting complicationssuch as bronchiolitis obliterans syndrome (BOS) may develop in up to 15% of cancer survivors. BOS may lead to lungfunction decline, worsening of quality-of-life, and death. The current definition of BOS does not capture the disease atan early stage in which it may be treatable and is suboptimal for the medical care of cancer survivors. In this project,Dr. Shah seeks to develop a new definition of BOS which would help clinicians identify it at an early disease stage. Theinvestigators aim to better define BOS by identifying the level of decline of lung function that corresponds with highermortality. Various risk factors for BOS will also be studied, including having viral pneumonia or not receiving treatmentfor viral infection at an early stage. This work will help clinicians to identify cancer survivors who may have early stagedisease that may be treatable.
MD Anderson symptom inventory, skill base module: Developing a disease specific instrument to evaluate quality of life in patients with skull base tumors
Shirley Su, M.B.B.S.
Patients with skull-base tumors often report significant reductions in quality-of-life, even many years after completingtreatment. However, very little is known regarding the quality-of-life profile for these patients and there are very fewinstruments specific to this disease that can provide researchers with the needed data and information. The goal of thisproject is to deliver a user-friendly, universally applicable and validated instrument for use in clinical care and research.The investigators plan to develop a skull-base-specific module of the MD Anderson Symptom Inventory. This modulewould rate the severity of numerous general and disease-specific symptoms on a scale of 1-10. The instrument proposedin this work will help standardize reporting in research and identify targets for improvement. And it will likely have significant impact on clinical practice by facilitating monitoring of patients and early intervention.
Lori Williams, Ph.D.
New cancer drugs are often extremely expensive. But generic versions of these drugs, once they become available,are usually cheaper and can ease the financial burden associated with some cancer therapies. In order to make informeddecisions about switching to generic drugs, information about their side effects, effectiveness against the cancer andfinancial costs is needed. The drug Gleevec® is used to treat chronic myeloid leukemia (CML) and its generic version,imatinib, became available in 2016. This provides an ideal opportunity to begin to understand the impact on patients of aswitch in the new cancer therapies from brand-name to generic drugs. The primary aim of this research is to explore anydifferences in symptom burden in survivors with CML who remain on long-term, name-brand Gleevec® versus those who change to generic imatinib.
Human papillomavirus (HPV)-associated second malignancies in patients who receive allogeneic stem cell transplantation
Jessica Hwang, M.D., M.P.H.
Patients with cancer may harbor asymptomatic, but cancer-causing human papillomavirus (HPV) infection. Stem cell transplantation increases the risk of HPV-associated second malignancies such as oropharyngeal, cervical, and anal cancer; survivors of allogeneic stem cell transplantation are especially at risk and need intensive HPV screening and management strategies to prevent HPV-associated second cancers. This proposal will determine the incidence and predictors of HPV-associated second malignancies after allogeneic stem cell transplantation and establish the prevalence of high-risk HPV types among survivors. Data from this proposal will be used to determine the utilization of HPV vaccines to prevent HPV-associated second malignancies in all allogeneic stem cell transplantation survivors.
Ju-Seog Lee, Ph.D.
Hepatocellular carcinoma (HCC) is accountable for an estimated 600,000 world-wide deaths annually and its incidence rates in USA have been doubled over the past 25 years (35,660 estimated new cases in 2015), and are expected to double over the next 10 to 20 years. Surgical resection is major curative treatment of patients with HCC. However, the long-term results of such curative therapies are far from satisfactory, because of the high rate of intrahepatic recurrence. In previous study, we identified unique gene expression signature that can identify high risk patients developing new HCC after treatment. However, liver biopsy, that is necessary for generation of gene expression data, is costly and frequently discouraged due to risk and potential complication during biopsy. In proposed study, we will screen candidate plasma markers to identify markers that are most significantly associated with high risk of HCC development and validate identified markers in independent cohorts of patients. Identified markers will significantly improve the management of patients with HCC.
Petra den Hollander, Ph.D.
Triple-negative breast cancer (TNBC) (between 15-20% of all breast cancers) affects young women and is more aggressive and deadly than ER-positive breast cancer. Selective agents currently used for the prevention and treatment of breast cancer are very effective in ER-positive breast cancer, but these agents are not effective in TNBC. For this large group of women, there is a critical need to develop new and more targeted therapies. To develop targeted therapies for TNBC, we need to identify what ‘drives’ this cancer, and what alterations these ‘drivers’ induce in the cancer cells. With the proposed studies we will identify the role of the signaling protein PTP4A3 in the development and progression of TNBC, and identify altered pathways and interacting proteins of PTP4A3. These findings will enable us to develop targeted, effective treatments for women at high risk for TNBC and women diagnosed with the disease.
Scott Kopetz, M.D., Ph.D.
In the US, more than 130,000 individuals will be diagnosed with colorectal cancer (CRC) and more than 50,000 will die from this disease in 2014. It is estimated that regular aspirin use has the potential to reduce the new cases of CRC by approximately 20% and reduce death from this disease by 35%. However, a safer aspirin is needed, as the risks associated with regular aspirin use currently outweigh the benefits. A new, safer aspirin was recently approved by the FDA, but has not yet been tested for CRC prevention. Our project will test this new, safer aspirin for use as a CRC prevention agent in animal models. If this new aspirin is effective and safer in animal models, then we will have the evidence and rationale to begin a clinical trial in humans. If the new aspirin is not effective in animal models, or not safer, then we will know not to pursue this drug for CRC prevention in humans. Broader use of a safer aspirin for CRC prevention has the potential to greatly reduce the burden of this disease.
Lorna McNeill, Ph.D., M.P.H.
Obesity continues to be highly prevalent in the African American (AA) population, affecting nearly 40% of AA men and a staggering 59% of AA women. Unfortunately this trend is also present in AA children and adolescents, resulting in AA children to likely face a lifelong struggle with obesity and increased cancer risk. Called "food deserts," areas without access to healthy food options have been shown to be more prevalent in African American neighborhoods and are associated with obesity. The proposed study aims to use a community-based approach to expand the Project CHURCH partnership to engage faith-based communities, the Houston Food Bank, the Brighter Bites program, and MD Anderson Cancer Center in utilizing churches as an effective food co-op concept to provide consistent access to fresh fruits and vegetables using low-cost strategies combined with nutrition education to low-income African American children and their families, thereby addressing cancer-related health disparities among African Americans in Houston.
Katherine A. Hutcheson, Ph.D.
Chronic aspiration is a life-threatening survivorship issue, affecting up to 30% of patients treated with curative radiotherapy for head and neck cancers. Aspirators are almost 5-times more likely to develop pneumonia than non-aspirators, and pneumonia confers a 42% increased risk of mortality among head and neck cancer survivors. While swallowing therapies positively impact on quality of life and scope of oral diet, there is no effective treatment to reverse chronic radiation associated aspiration. Expiratory muscle strength training (EMST) shows promise as a treatment for aspiration in other challenging pathologies such as dysphagia associated with progressive neurodegenerative disease. The long-term goal of this work is to prevent pneumonia in chronic aspirators after head and neck radiotherapy. The objectives of the pilot studies in this application are to estimate the underlying mechanism, effect size, feasibility, and acceptability of EMST as a therapeutic approach for chronic aspiration after head and neck radiotherapy.
Carol M. Lewis, M.D., M.P.H.
Current Head and Neck Cancer (HNC) post-treatment surveillance practices have not been evaluated. Significant long-term sequelae of HNC and its treatment include dysphagia, speech impairment, lymphedema, osteoradionecrosis, and diminished quality of life. According to the findings of a recent study, as many as 45 percent of late HNC treatment sequelae go unreported. Post-treatment surveillance patterns and functional rehabilitation utilization for HNC have not been studied systematically. Addressing this knowledge gap is critical to identifying optimal post-treatment surveillance strategies that incorporate interventions for these treatment-related functional impairments. The long-term goal is to improve HNC survivorship care. The overall objective of this project to describe and quantify institutional and national patterns of HNC post-treatment surveillance and resource utilization, while identifying predictors of resource use and corresponding long-term functional outcomes.
Risk modeling and predictive biomarker discovery for therapy related myeloid neoplasms risk in breast cancer patients
Joseph D. Khoury, M.D.
Patients who receive cytotoxic chemotherapy and/or radiation therapy for breast cancer are at risk of developing therapy-related myeloid neoplasms (t-MN). Notably, breast cancer is the most common malignant solid tumor among patients with t-MN. Thus, in addition to its primary effect as a public health burden, breast cancer exerts an additional adverse effect through t-MN. Accordingly, we premise that developing predictive tools to assess the risk of t-MN development in any given 16 MD Anderson Cancer Center patient can inform risk-modulated therapy decisions that should ultimately reduce the risk of secondary malignancies among susceptible breast cancer survivors. The aims of this study are to identify acquired and/or inherited genomic alterations that predispose some breast cancer patients to development of t-MN; and to create a biomarker-based predictive model to identify such a predisposition to secondary myeloid neoplasms among breast cancer patients.
Using telemonitoring to optimize the mobility of cancer survivors with skeletal metastases after surgery to preserve limb function
Robert L. Satcher, Jr., M.D., Ph.D.
The use of mobile devices has the potential to improve the delivery of cost effective, high-quality, standardized surveillance of cancer survivors. New technological developments in telecommunications have allowed HIPAA-compliant telemonitoring of patients; however, the Center for Medicare and Medicaid Services(CMS) has requested demonstration of equivalence to an in-person clinic visit. In contrast to other medical subspecialties, long-term survivorship research on patients after surgery using mobile devices has been uncommon. This study proposes to develop and test a novel web-based and mobile technology for surveillance of cancer survivors following surgery for bone metastases.
Carrie Daniel-MacDougall, Ph.D., M.P.H.
Bacteria residing in the gut have been linked to diet, energy balance and obesity, all of which are key exposures involved in the development of colon polyps and cancer. Our study takes an integrative approach to comprehensively investigate the link between the vast community of gut bacteria (or microbiome), obesity, and the risk of colorectal polyps. In the long-term, this research will inform the development of non-invasive screening tools and future intervention trials targeting favorable changes in gut bacteria to reduce obesity and colorectal cancer.
Guang Peng, M.D., Ph.D.
One of the most earliest and universal genetic alterations observed in pancreatic cancer is activating mutations in the KRAS oncogene, which are present in 90%-95% of cases. In this project, we will work to develop a novel strategy for pancreatic cancer prevention by targeting replication stress, a molecular property of premalignant that is acquired as a result of KRAS oncogene activation instead of targeting KRAS oncoprotein itself. The overall objective of this proposal to systematically identify chemical inhibitors of DNA2, a key molecular node of the DNA repair network, upon which premalignant and cancer cells with KRAS oncogene-induced replication stress depend for survival. It is anticipated that we will discover novel DNA2 inhibitors from this study, which can be used as a new class of chemopreventive agents with exquisite selectivity against premalignant cells with KRAS oncogene-induced replication stress but sparing normal cells.
Challenging choices: Developing a decision aid to help women with cancer make good decisions about fertility preservation
Terri Woodard, M.D.
Cancer-related infertility causes emotional distress, even as long as ten years after successful cancer treatment. Many women have difficulty making a decision about whether to preserve fertility or not. The purpose of this research is to design and produce a web-based decision aid that helps women make decisions that are consistent with their personal values. By providing this support, we can alleviate and prevent emotional distress, improving the survivorship experience of women with cancer.
Improving quality of life of cancer survivors through the identification of treatment targets for cancer-related fatigue
Robert Dantzer, Ph.D., D.V.M.
Fatigue is a very common symptom in cancer survivors. However, the experience of fatigue is complex. It involves alterations in motivational and cognitive processes that still need to be characterized. It is the objective of our current research project to characterize these alterations in order to improve our understanding of how to treat fatigue.
Evaluation of risk factors in predicting fractures following hematopoietic stem cell transplantation in patients with underlying hematologic malignancies
Huifang Liu, M.D., Ph.D.
In the last decade the number of long-term survivors of hematopoietic stem cell transplantation (HSCT) has increased, resulting in a large population experiencing from effects of HSCT and its associated treatment. Rapid bone loss, which can lead to fractures, is common following HSCT. We found 8% patients suffer a fracture after their transplantation, which is approximately 10 times higher in 45 to 64 year old males and females comparing to the general population. Fractures are associated with significant morbidity and mortality and worsen the quality of life of long-term survivors. In spite of the high rate of fractures, the best way to identify HSCT recipients at high risk for fracture is unknown, but is crucial in clinical practice while considering preventative treatment. The Survivorship Seed grant from the Duncan family will help us to close the gap in knowledge.
Benjamin Smith, M.D.
In our project, we will partner with Centers for Medicare and Medicaid Services to survey a nationally representative, population-based sample of older women who are breast cancer survivors. We will use validated instruments to determine how breast cancer and its treatment have impacted these survivors, both positively and negatively. We will also assess quality of life and the patient experience of their treatment outcome. The influence of treatment choices, for example, the choice of lumpectomy versus mastectomy, on long-term quality of life outcomes will also be assessed. The pilot data generated through this project will support grant applications to conduct a large scale survey of breast cancer survivors, with the ultimate goal of facilitating better treatment decision making geared toward optimizing patients’ long-term survivorship experience.
Said Akli, Ph.D.
Triple negative breast cancer patients have limited treatment options outside of non-specific standard chemotherapy. Recent studies from our laboratory establish that short forms of cyclin E are over-expressed in 70% of all triple negative breast cancer and that mice expressing those forms are completely protected against breast cancer when Cdk2 is not expressed. Seliciclib and dinaciclib are potent inhibitors of Cdk2 and we would like to test in this proposal if these drugs can prevent breast cancer in our mouse model. Furthermore, we will identify the genes whose expression will be modulated by the two Cdk inhibitors treatment in vivo using gene expression microarrays and biomarker analysis. The results of this study should provide the preclinical rationale for the development of cyclin-dependent kinase inhibitors for the prevention of human triple negative breast cancer especially those with LMW-E overexpression.
The role of LONGf, a novel long non-coding RNA encompassing the risk SNP rs6983267, in colorectal cancer predisposition
George Calin, M.D., Ph.D.
Colorectal cancer (CRC) predisposition is not fully understood, as the majority of patients with familial CRC that cannot be included in the Mendelian syndromes do not have a known genetic etiology. The proposed study on the involvement of a gene that did not codify for a protein and therefore named a non-coding RNA in CRC predisposition is innovative as CCAT2 (Colorectal Cancer Associate Transcript 2), could be the “long searched” elusive factor in CRC predisposition. This is located over the genetic variant rs6983267, a single nucleotide polymorphism (SNP) on chromosome 8q24 located outside any coding genes. The central hypothesis of this proposal is that CCAT2 could be involved in the CRC predisposition and increase the risk for CRC in the individuals with risk variant (G) of rs6983267. In this application we will identify the clinical significance of CCAT2 in CRC predisposition by using a large cohort of RNA samples from the Familial Cancer Registry, and will demonstrate the CCAT2 involvement in CRC predisposition using a transgenic mouse model. The identification of the roles of CCAT2 in the predisposition to CRC will not only offer new insights into the molecular mechanisms and signal transduction pathways altered in CRCs but will also be of great clinical significance in identifying new diagnostic molecular markers of colorectal cancer risk and offering potential target for prevention.
Paul Scheet, Ph.D.
The vast majority of skin cancers, which affects millions of individuals annually, can be attributed to excessive, but preventable, UV radiation exposure. While population-based screening for skin cancer is effective at reducing skin cancer mortality, it is impractical and expensive. In our study, we propose a DNA-based method to identify individuals most at risk for developing skin cancer. Using chronic UV exposed human skin tissue and mouse models will characterize the effect of UV exposure on genetic mosaicism, the existence of heterogeneous mixtures of cells, which will serve as a marker for risk, and which may ultimately be used to identify individuals most in need of high surveillance.
Eduardo Vilar-Sanchez, M.D., Ph.D.
Familial Adenomatous Polyposis (FAP) is a genetic condition that is diagnosed when a person develops more than 100 premalignant polyps in the colon and rectum. The average age for polyps to develop in patients diagnosed with FAP is in the mid-teens and more than 95% will have multiple polyps by age 35. If FAP is not recognized and preventive measures are taken, there is almost 100% chance for this patient population to develop colorectal cancer. In addition, the study of polyps in FAP offers a model to understand the transition from normal colonic epithelium into premalignant stages and later colon cancer development in populations at average risk. Therefore, our proposed studies to identify important genetic alterations that result in polyp formation in FAP represents an opportunity to identify new preventive measures not only for patients and families with this condition but also open an opportunity to be translated to the general population.
Qiang Shen, M.D., Ph.D.
Prevention of ER-negative breast cancer constitutes a clinical obstacle that greatly impedes the effort to reduce breast cancer incidence and mortality. In fact, all ER-negative breast cancers and a significant portion of ER-positive breast cancers are not preventable using currently available preventive drugs. This research chooses the STAT3 transcription factor as a new cancer prevention target based on the preliminary studies that STAT3 is activated in pre-cancer breast cells and mammary glands. We propose to use newly created, orally active inhibitors to suppress STAT3 activation in transgenic mouse models that develop ER-negative mammary tumors highly representing human breast cancers. Thus, this project has significant potential to lead to a reduction in breast cancer incidence and/or mortality within next decade. Successfully carried out, this project may bring 1-2 potent, well-characterized, highly optimized, orally active STAT3 inhibitors into advanced preclinical development as a new class of preventive agents for prevention of many types of human cancer including ER-positive and ER-negative breast cancers.
Dihua Yu, M.D., Ph.D.
Breast cancer is one of the most common women’s cancers in the US and one in eight women develops breast cancer during their lifetime. The most effective way to reduce breast cancer mortality is prevention of early disease; therefore, it is very important to develop early detection and intervention strategies. Tamoxifen (Tam) has been successfully used in the prevention of estrogen receptor (ER) positive breast cancers. However, no agents could effectively prevent ER negative (ER-) breast cancer. We have identified key molecular alterations in ER- breast lesions and will test whether we could effectively prevent ER- breast cancer by targeting these alterations using specific targeting agents. If successful, our findings can be translated to the clinic to prevent ER- breast cancer in high risk women.
Ala Abudayyeh, M.D.
BK virus is a non-enveloped, encapsulated DNA virus that belongs to the Papovaviridae family. It has been increasingly being recognized as an important outcome predictor when the cellular immune system is impaired, particularly after renal and hemopoietic stem-cell transplantation (HSCT). It occurs in up to 70% of hematopoietic stem cell transplant (SCT) survivors and is associated with prolonged hospitalization leading to severe hematuria in 8-27%. In this study, we will retrospectively review the Stem cell transplant survivors at MDACC to prove the hypothesis that BK virus infection is a marker of poor renal outcomes and overall poor patient prognosis in the SCT survivor population. By focusing on BK virus infection in the HSCT survivor population and its renal and overall survival outcome would help formulate better screening and prevention protocols.
Does radical therapy result in substantial long term (>2yrs) sexual and urinary functional decline compared to active surveillance in men diagnosed with prostate cancer?
Brian Chapin, M.D.
Good clinical care of patients with prostate cancer includes careful and standardized assessment of functional and oncologic outcomes. Current research practice for survivorship outcomes in patients with prostate cancer lacks standardization. The well-known side effects after the surgical treatment of prostate cancer that can affect a survivor’s quality of life are erectile dysfunction and urinary incontinence. The long term social and psychological impact and the realization that many prostate cancers have minimal lethal potential, have led to active surveillance programs for low/intermediate risk disease. This too has the potential for significant psychological, physical and possibly oncologic sequelae. The primary goal of this study is to compare long term (>3yrs) sexual and urinary functional outcomes in patients with and without radical therapy for low/intermediate risk disease. Measurements will be made using a web based, validated, standardized, patient- reported quality of life questionnaire. This will allow for us to determine if long term functional outcomes after surgery are durable and whether they differ from the natural decline in function as a result of aging. This will aid in the counseling and long term care of patients with prostate cancer.
Diane Bodurka, M.D., M.P.H.
This study focuses on the health care needs and expectations of gynecologic cancer survivors. As the number of cancer survivors continues to grow, it is critical to identify physicians who will take care of these patients after the surveillance period. In this mixed methods (quantitative and qualitative) study, we plan to evaluate the preferences of gynecologic cancer survivors for follow-up care (oncologists vs OB/GYNs) and identify the support and resources OB/GYNs need to broaden access for gynecologic survivorship care in the community. Our study will be among the first to identify barriers and challenges to community-based survivorship care for women with a history of gynecologic cancer and will specifically evaluate age-related barriers to survivorship care from the perspectives of both health care providers and patients. This is an essential first step toward transforming the health care system to accommodate the growing ranks of long-term survivors.
Feasibility of a couple vs an individual-oriented mood management intervention for distressed lung cancer patient
Cindy Carmack, Ph.D.
Psychosocial interventions are important to the care of cancer survivors because of the negative effects psychological distress can have on patient quality of life and health status. Including the spouse in the delivery of psychosocial interventions may have benefits for both the patient and the spouse. Patients may adopt new health behaviors and follow treatment recommendations more reliably, resulting in a positive impact on their health. Spouses may experience health benefits in the form of reduced caregiver burden, improved health behaviors (e.g., smoking) and promotion of a healthy bereavement following the patient’s death. Using a web-based counseling approach to deliver psychosocial intervention may result in greater outreach for underserved couples, and may be easily integrated into cancer care. In this study, we will pilot test a web-based couple-oriented counseling intervention compared to a web-based patient only counseling intervention in 40 lung cancer patients who are experiencing psychological distress. We will explore the effects of both interventions on patient psychological functioning, health behaviors, treatment adherence, and symptom burden and on spouse psychological functioning, health behaviors, and caregiver burden.
Jae-Il Park, Ph.D.
We will study a novel molecule that is only detected in colon cancer and positively controls tumor promoting Wnt signaling pathway. This research is relevant to public health because elucidating the fundamental mechanism of cancer development is expected to provide a valuable basic concept and new model for cancer prevention, diagnosis, and treatment. The proposed research addresses the central issues that are important to understanding the underlying mechanisms of colon cancer development. In this project, we will (1) determine the role of a newly identified Wnt agonist in regulating tumor development and (2) further develop the efficient neutralizing methods.
Susan Peterson, Ph.D., M.P.H.
Genetic testing for hereditary cancers is now part of standard oncology care, yet there are barriers to realizing its full benefits for patients and families. Studies consistently show that information about genetic risk may not be completely or accurately disseminated within families, and that families may grapple with the nuances and complexities of conveying genetic risk information. To address these issues, we propose an intervention, called My Family Garden, a web-based, secure social networking tool to enable the collection and sharing of family history and cancer risk information in families with hereditary cancer. Funding from the Duncan Family Institute will support the development, testing, and evaluation of a prototype system for My Family Garden. Long-term scientific goals include evaluating the efficacy of My Family Garden in enabling comprehensive communication of cancer risk information and adoption of cancer risk reduction strategies in high risk families.
Leslie Schover, Ph.D.
Aromatase inhibitors have become the hormone therapy of choice for postmenopausal women with estrogen-positive breast cancer and will increasingly be prescribed to prevent breast cancer after menopause. Yet, 10% to 25% of women discontinue aromatase inhibitors in the first year of treatment because of negative side effects. Sexual problems are among the most distressing symptoms. Our study will survey women who began aromatase inhibitors in the past 12 to 18 months about changes in their sex lives. Their experiences will be compared to those of sexually active women assigned randomly when they start treatment to one of two groups: 1) usual care plus some brief, written brochures about sexual function or 2)access to an internet-based sexual counseling program supplemented with phone counseling. Two new vaginal moisturizers will also be compared in the counseled group. We want to see if staying sexually active and avoiding painful vaginal dryness will prevent more severe sexual problems and improve women’s ability to keep taking their aromatase inhibitors.
REcovery of the left ventricular dysfunction in CAncer Patients (RECAP trial) health status and health behaviors among cancer survivors: A population based study
Anecita Fadol, Ph.D.
The REcovery of left ventricular dysfunction in CAncer Patients (RECAP trial) is a pilot study about cancer survivors who developed heart failure while receiving cancer treatment. Some patients recover from heart failure with heart medicines. The current practice is for patients to take these heart medicines for life, because there is no data as to what will happen if patients stop taking the heart medicines after heart function improves. This study will examine if it is safe to stop these heart medicines in cancer survivors after the heart function returns to normal. The findings from this study will provide baseline information for a future large study to provide evidence to potentially change clinical practice and improve the cancer survivor’s quality of life.
Angeles Lopez-Olivo, M.D., Ph.D.
Bone health can prevent osteoporosis, one of the most frequent and potentially serious complications of cancer and cancer therapy. This project will develop an interactive web page containing bone health information tailored to the needs of breast and prostate cancer survivors. The goal of the project is to improve patients’ knowledge, self-management and awareness of bone health issues, and ultimately reduce the risk of fracture in cancer survivors.
Susan Peterson, Ph.D., M.P.H.
The need for improved survivorship care to prevent the recurrence of cancer among survivors and to improve their quality of life has been widely recognized. The use of patient navigators is a promising approach to help survivors manage their survivorship care; however, relatively little is known about the efficacy of cancer survivorship navigation programs. Our project assesses breast cancer survivors’ navigation needs and preferences for a navigation program within the Survivorship Clinic at Lyndon B. Johnson Hospital in Houston. We also will interview clinic stakeholders to get their perspectives on the integration of this kind of program without disrupting clinic flow. Because the degree to which clinical staff can take on navigator roles is limited due to time and patient care demands, we also will assess whether personal health information systems and e-Health Technology (specifically, the HealthATM platform) can be leveraged to increase the effectiveness and sustainability of navigator efforts.
Nancy You, M.D.
Providing high-quality care to cancer survivors represents a new challenge in cancer care. However, we know little about how patients do and what cares they receive once they finish the often intense cancer-directed treatments and enter what is termed "the extended phase of survivorship". Our project will help us learn these patient experiences and then develop ways that will help us measure the quality of care being delivered to survivors.
Pilot test of a lifestyle intervention arm in an endometrial cancer prevention trial: Effects on endometrial proliferation and related biomarkers
Karen Basen-Engquist, Ph.D., M.P.H.
Women who are obese and have low levels of physical activity are more likely to develop endometrial cancer (cancer of the lining of the uterus), but we do not yet know if losing weight and becoming more active will decrease a woman’s risk of this disease. The goal of our research is to answer this question.We are collaborating with investigators from MD Anderson’s SPORE (Specialized Program for Research Excellence) in uterine cancer who are doing a trial to test whether metformin, a drug usually used to treat diabetes, can help reduce cell growth in the endometrium of women who are obese. We will add another arm to this trial in which the participants will receive a diet and exercise program to help them lose weight. All women participating in the SPORE study will have endometrial biopsies to assess cell growth as well as blood tests to measure markers that may be related to the risk of developing endometrial cancer. This pilot study will help us determine whether there is enough evidence to show that changing diet and exercise behavior affect s endometrial cancer risk and, if so, justify doing a larger clinical trial. See video describing Dr. Basen-Engquist's work
A feasibility study for high-throughput application of a novel early detection and risk assessment biomarker
Randa El-Zein, M.D., Ph.D.
In this study, we will test the feasibility of automating a biomarker that comprehensively allows the measurement of cellular genomic instability. We have shown that cytokinesis blocked micronucleus assay is a sensitive predictor of lung cancer risk. Automation of this powerful assay will provide a strong, rapid and unbiased quantitative analysis tool for cancer risk assessment. We envision using this biomarker in lung cancer screening programs as a prescreening tool for current and former smokers prior to CT screening. This prescreen will allow the identification of individuals at high risk of development of lung cancer, and who therefore warrant further screening and follow-up using CT. Given the low cost, accuracy and safety, this biomarker test could be potentially valuable for screening of large populations. See video describing Dr. El-Zein's work
Identifying neurocognitive risk markers that differentiate smokers from never-smokers and ex-smokers
Jason Robinson, Ph.D.
Even though most smokers know that smoking is unhealthy, and despite most wanting to quit, only 6% of those who make a serious quit attempt are still abstinent one year later. The problem is that smoking, like other drugs of abuse, alters the brain after repeated use, alterations that make it difficult to quit and to stay abstinent. We want to examine whether brain markers that we previously identified in smokers exist in never smokers and ex-smokers. The ultimate goals of the grants that will result from this proposal would be to use these brain markers to predict which nonsmokers are at risk from becoming smokers and which ex-smokers are likely to have problems staying abstinent.
Integrative genomic analysis of actinic keratoses: Using inter-lesional and cross species analysis to predict progression to cutaneous squamous cell carcinoma
Kenneth Tsai, M.D., Ph.D.
Skin cancer is the most common malignancy in humans, of which there are over 3 million cases a year in the United States, costing an estimated $500 million in treatment-related costs and $2 billion in overall economic impact. Cutaneous squamous cell carcinoma (the 2nd most common skin cancer) has a well-ordered sequence of development beginning with chronically sun-exposed skin, progressing to the most common precancerous lesion in humans, the actinic keratosis (AK), and then ultimately to invasive cancer. The tremendously high incidence of AK presents a vast opportunity for secondary skin cancer prevention, and our proposed studies to identify the important genetic alterations that result in AK formation will enable the design of better interventions to eliminate them and prevent their progression to cancer. See video describing Dr. Tsai's work
Ivan Uray, M.D., Ph.D.
The two most fundamental criteria for the development of cancer preventive agents are achieving high effectiveness and low toxicities associated with chemopreventive medication, typically administered over a long period of time. The proposed research addresses both issues. Its goal is to identify drug combinations which more effectively suppress cell growth and prevent cancer than either individual component alone. At the same time this research will develop new treatment options that reduce the effective dosage by combining cancer preventive agents to achieve equivalent or synergistic effects. Achieving these goals may have a tremendous impact on the acceptance of pharmacologic preventive strategies.
Xiangwei Wu, Ph.D.
Pancreatic cancer is often diagnosed at an advanced stage and has a poor prognosis. Activating mutations of the K-ras oncogene are possibly the single most common genetic abnormality in pancreatic cancer. Therefore, mutant K-ras gene or its gene product represents an obvious target for the treatment and prevention of pancreatic cancer. In this application, we propose to develop a novel method to specifically abolish oncogenic K-ras expressing cells for pancreatic cancer prevention and treatment.
Germline genetic variants in the Wnt/beta-catenin stem cell pathway as predictors of colorectal cancer risk
Michelle Hildebrandt, Ph.D.
Colorectal cancer is the 3rd most common malignancy with nearly 150,000 new cases diagnosed each year in the United States. These studies will shed light on the effect of common, germline genetic variation within the Wnt/beta-catenin stem-cell signaling pathway on colorectal cancer risk. The results can contribute to a personalized risk prediction model that will help to understand an individual’s risk of colorectal cancer development and provide recommendations of suitable prevention strategies with the goal of reducing the incidence and burden of this deadly disease.
Yanhong Liu, Ph.D.
Gliomas, the most common type of brain tumors, have very poor prognosis and are associated with considerable morbidity and mortality. Investigators have long known that gliomas are more common in Caucasians than in African Americans and Hispanic Americans. The proposed research focuses on discovering genetic markers among African Americans and Hispanic Americans populations. This research will help explain why glioma affects Caucasians more often than African Americans and Hispanic Americans, and will potentially lead to new and improved modes of diagnosis and prevention for patients with glioma.
Ashraful Hoque, M.D., Ph.D.
The purpose of this research study is to investigate the role of essential and toxic trace metals and their association with prostate cancer among African American and white men. Researchers in Dr. Hoque’s laboratory will measure levels of essential and toxic metals in blood among both prostate cancer patients and healthy men to determine if there is an association of low levels of essential or high levels of toxic metals with prostate cancer. In addition, Dr. Hoque’s group will examine whether certain dietary factors, such as fruit and vegetable consumption and dietary supplements, reduce the toxic effects of heavy metals and ultimately decrease prostate cancer risk. Data generated from this study could have significant public health implications through the identification of a population with deficient essential trace metals that could be at high risk for prostate cancer and, therefore, could benefit from targeted primary and secondary prevention interventions.
Bo Peng, Ph.D.
Many genetic risk factors have been identified for complex human diseases such as lung cancer but it is unclear how to make effective use of such information to improve existing cancer prevention strategies. This study aims to simulate populations with realistic environmental and genetic risk factors of cancers, and then study the cost-effectiveness of novel cancer prevention strategies that make use of individual genetic information. By predicting and comparing the benefits, harms, and costs of various cancer prevention strategies, the results of this project could contribute to development of tools to help clinicians make recommendations regarding the benefits of genetic testing for individuals who are at risk for certain types of cancers, and, ultimately, aid clinicians in providing individualized cancer prevention and treatment options according to a patient’s individual genetic profile.
Linda Elting, Dr. P.H.
Little data exists regarding the health status and experiences of cancer survivors, particularly for survivors of the less common cancers and of racial and ethnic minority populations. The Behavioral Risk Factor Surveillance System (BRFSS) is an annual telephone survey conducted by the Centers for Disease Control (CDC) that collects data regarding various health conditions and risk behaviors in the U.S. population. We propose to use data from the 2009 and 2010 BRFSS surveys regarding health problems and behaviors in cancer survivors to identify subgroups of survivors who are likely to benefit from interventions based on their needs. Using these data, we will estimate the prevalence of certain health problems and health behaviors in cancer survivors and in a group of control individuals without cancer. We will also examine differences in the prevalence of these health conditions and behaviors among various subgroups of the survivor population. This work will provide estimates of the public health significance of cancer survivorship issues within the U.S. Such estimates are critical to the design of future intervention studies, guidelines and collaborative care models for cancer survivors.
Toward an understanding of body image adaptation following surgical treatment for head and neck cancer
Michelle Fingeret, Ph.D.
Body image is recognized as a critical psychosocial issue for individuals with head and neck cancer. The purpose of this study is to determine how such patients make sense of their appearance and body image changes after surgery. We will conduct interviews with 20 patients and 15 healthcare providers. Our primary research questions involve examining the immediate emotional reactions and psychosocial ramifications of mirror-viewing during the acute postoperative phase, as well as developing an understanding of how these may change throughout the course of active treatment and into the period of survivorship. There will be a specific focus on obtaining data regarding current standards of care for assisting patients with mirror-viewing during and following treatment. The proposed work is anticipated to enhance knowledge regarding fundamental body image issues for the head and neck cancer patient population and can be used to guide future studies and the development of novel psychosocial interventions for this patient population.
The role of tryptophan metabolism in the chronic fatigue experienced by chronic myelogenous leukemia (CML) survivors
Jorge Cortes, M.D.
In order to avoid recurrence, survivors of chronic myelogenous leukemia (CML) must remain on tyrosine kinase inhibitor (TKI) therapy for years, if not for the remainder of their lives. Fatigue is recognized as one of the most common complications of this long-term therapy. The mechanism of this TKI-induced fatigue is currently unknown; however, recent studies suggest tryptophan degradation may play a role. Based on these studies, we propose an in-depth longitudinal study to track the temporal patterns of tryptophan degradation and its association with fatigue and QoL in CML survivors. We will measure the degree of association between tryptophan degradation and the incidence of fatigue as well as changes in QoL over time in CML survivors undergoing TKI therapy. We will also examine the impact of various CML treatments on such associations as well as assess which TKI maintenance therapy may be more suitable for older CML survivors based on their temporal patterns of tryptophan degradation, fatigue and QoL.
Francesco Versace, Ph.D.
More than half of breast-cancer survivors suffer from loss of sexual desire, particularly if they have had chemotherapy. This loss does not appear to correlate with serum androgen levels and pharmaceutical and sex therapy treatments have not had more than modest success in treating this loss of desire. Our hypothesis is that chemotherapy does long-term damage to the neural networks in the brain necessary for emotional processes. We will use functional magnetic resonance imaging (fMRI) in a pilot study of breast cancer survivors 40-60 years of age to measure brain activity while viewing standardized sets of pleasant, unpleasant and neutral pictures. Results of this study will lead to further research on the impact of chemotherapy on the brain’s emotional pathways and contribute to the design of future studies aimed at developing more effective remedies for the frequent problem of long-term loss of sexual desire in breast cancer survivors.
A brain-plasticity based computerized intervention to treat attention and memory problems in adult brain tumor survivors
Jeffrey Weffel, Ph.D.
Survival times have improved for individuals with brain tumors (BT), however, the majority of BT survivors suffer from cognitive impairment associated with reduced independence, decreased ability to participate in daily living activities, and increased caregiver distress. Rehabilitation in the form of compensatory training requiring intensive in-person therapy lasting weeks to months and involving multi-disciplinary teams of care providers is available to some, but not all, BT survivors due to geographic and financial reasons. The Brain Fitness Program (Posit Science, San Francisco, CA) is an at-home, web-accessible brain plasticity-based computerized intervention for improving cognitive function in the elderly that may be applicable to BT survivors. The goal of this proposal is to determine the feasibility and acceptability of the Brain Fitness Program in BT survivors, as measured by improvement in a directly trained measure from the Brain Fitness Program among BT survivors, as well as by changes in self-reported everyday cognitive function and in objective neuropsychological tests of attention and memory. These results will build the basis for developing and powering larger clinical trials to determine the efficacy and effectiveness of this broadly available intervention.
Imad Shureiqi, M.D.
Colon cancers are the second most common cause of cancer death in the United States. Despite progress that has been made, the death rates from colorectal cancers remain around 50%, and advanced colorectal cancers are generally incurable, with an average survival rate of approximately two years even with the best currently available treatment. Clearly, better interventions for the prevention and treatment of colorectal cancers are needed. Increased production of the protein peroxisome proliferator-activated receptor delta (PPAR-d) is associated with colon cancer development; however, it is yet to be determined if increased production of this protein in cancer cells promotes colon cancer development. The proposed project aims to address this question by simulating what happens in human colon cancer in mice that are genetically engineered to overproduce the protein in colon cells. This improved understanding is expected to determine if new drugs can be developed to target PPAR-d to prevent and treat colon cancer. See video describing Dr. Shureiqi's work
Chongjuan Wei, Ph.D.
Peutz–Jeghers syndrome (PJS) is a genetic disorder characterized by benign polyps called hamartomas which occur mainly in the stomach and small and large intestines. Patients with PJS are at higher risk for developing various types of cancer. To date, therapy for PJS has been limited to surgical removal of clinically significant polyps. Over-activation of mTOR signaling, a pathway which promotes cell growth and proliferation, has been associated with PJS suggesting that an mTOR inhibitory drug may be useful for PJS treatment. In this proposed project, we will use niclosamide, a novel mTOR inhibitor drug, to determine whether inhibition of mTOR signaling suppresses polyp formation in the PJS mouse model. Considering that the mTOR pathway is aberrantly activated in most common cancers in addition to PJS, the resulting findings could impact not only PJS prevention and treatment but also other cancers with dysregulated mTOR signaling. See video describing Dr. Wei's work
Xiaochun Xu, M.D., Ph.D.
The incidence of esophageal cancer, a deadly disease with a poor prognosis, has been increasing in the U.S. The actual origin of esophageal cancer remains unclear, but we do know esophageal cancer is more likely to occur in individuals who have frequent gastroesophageal reflux carrying acid, bile and protease, resulting in the formation of Barrett's esophagus. The latter is considered to be a premalignant condition that may lead to the advancement of esophageal cancer. Tobacco smoke can also enhance the effects of bile acid, which may in and of itself be a risk factor for esophageal cancer. These risk factors contribute to development of esophageal cancer by causing multiple genetic changes. In this study, in animal models, we will investigate how these risk factors contribute to esophageal cancer by blocking the activity altered genes to determine if these prevents or delays development of esophageal cancer and blocks the growth of esophageal cancer cells.
Yuanqing Ye, Ph.D.
Lung cancer is the leading cause for cancer-related death in the U.S., with almost 90% of lung cancers attributed to cigarette smoking. There is substantial evidence that the process of developing lung cancer is driven by the interaction between exposure to external cancer-causing substances and inherent genetic traits. This study will identify novel genetic variants in miRNA related genes, a type of RNA that plays important regulatory roles in many biological processes and diseases, and are associated with the development of lung cancer. We will explore gene-gene interactions and gene-environment interactions, use analytical and statistical techniques to then develop and validate models, which will help to identify individuals at highest risk for lung cancer who then may be prospects for targeted prevention interventions. The results of this study may shed significant light into a cause of lung cancer and lead to new techniques to identify those at high-risk for this disease. See video describing Dr. Ye's work