The Interplay of Behavior, Environment, and Microbiota in Colorectal Cancer Risk

行为、环境和微生物群在结直肠癌风险中的相互作用

• 批准号: 8967533
• 负责人: Tiffany LaShaun Carson
• 金额: $ 14.61万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8967533
• 关键词: Accounting; Address; Age; Alabama; Alcohol consumption; Antibiotics; Bacteria; Behavior; Behavior Therapy; Behavioral; Bioinformatics; Biological; Blood; Cancer Burden; Cancer Etiology; Case-Control Studies; Cessation of life; Chronic Disease; Clinic; Clinical; Colorectal Cancer; Communities; Consumption; Control Groups; Data; Development; Diagnosis; Diet; Early Diagnosis; Environment; Environmental Risk Factor; Epidemiologist; Ethnic group; Family; Fatty acid glycerol esters; Feces; Female; Funding; Future; Gender; Goals; Grant; Health; Health Care Costs; Healthcare; Hour; Human; Incidence; Inflammatory Bowel Diseases; Inflammatory Response; Intervention; Lead; Life Style; Link; Literature; Malignant Neoplasms; Meat; Mediating; Mentors; Metabolism; Microbe; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Oral; Outcome; Participant; Physical activity; Population; Prevalence; Prevention; Process; Psychological Stress; Public Health; Publications; Publishing; Race; Recommendation; Recording of previous events; Recruitment Activity; Reporting; Research; Research Design; Research Personnel; Research Project Grants; Research Training; Risk; Risk Factors; Saliva; Sampling; Science; Smoking; Specimen; Stress; Structure; Surveys; Taxon; Techniques; Testing; Training; United States; Universities; Woman; Work; Writing; base; cancer health disparity; cancer risk; career; career development; colon cancer patients; cost; evidence base; experience; gut microbiota; health disparity; improved; innovation; insight; lifestyle factors; male; men; microbial; mortality; novel; pathogenic bacteria; racial and ethnic; racial difference; research study; screening; sex; skills; stress management

 DESCRIPTION (provided by applicant): Dr. Tiffany Carson is an applied epidemiologist with a background in studying health disparities of black and white women. Dr. Carson's early work focused on behaviors related to diet, physical activity, obesity and related health outcomes. Recently, Dr. Carson has focused on applying her research efforts to better understand cancer disparities of black and white women. Dr. Carson's overarching career goal is to become an independently funded investigator and develop evidence-based bio-behavioral interventions to reduce cancer health disparities. To that end, this application proposes a rigorous research project and training plan focused on investigating the microbiota as a novel potential contributor to colorectal cancer (CRC) disparities between black and white women. CRC is the 2nd leading cause of cancer death in the United States accounting for 9% of cancer deaths. Known risk factors for CRC include increasing age, male sex, family history, inflammatory bowel disease, type 2 diabetes, alcohol consumption, smoking, physical inactivity, high consumption of red and processed meats and high fat diet, and obesity. Among women, even after accounting for differences in the distribution of risk factors, black women remain at 48% greater risk for CRC than white women. There is a growing body of research suggesting that the influence of diet on CRC risk is mediated through the microbiota and that microbial perturbations caused by diet, lifestyle, and antibiotics can lead to increased risk for CRC and other chronic diseases. Stress is one factor that has been shown to lead to alterations in the microbiota. Our research has shown that black women report moderate to high stress levels and additional published literature indicates that black women report higher stress levels than their white counterparts. These observations have lead to our hypothesis that a greater proportion of black women have a perturbed microbiota as a result of higher stress levels compared to white women, putting black women at greater risk for developing CRC. In the present proposal, we plan to explore this hypothesis employing a case control study design comparing the following groups: 1) black and white women with incident CRC from the Kirklin Clinic at UAB and 2) age-matched cancer-free black and white female community controls. Specifically, we will first characterize the oral and gut microbiota of black and white women with CRC and compare by race with particular focus on microbes known to be either positively or negatively associated with CRC. Because all cases will have CRC, we hypothesize that there will be no significant racial differences in the microbiota or other known risk factors for CRC such as diet. In contrast, when we repeat this experiment in cancer-free black and white female community controls, we expect to observe racial differences in the microbiota, with black women having less health-promoting bacteria and more pathogenic bacteria than white women, which would put black women at increased risk for CRC. We anticipate that a greater proportion of black females in the control group will have microbiota that resembles the microbiota of participants with CRC. Additionally, if our hypothesis is supported, psychological stress with be inversely associated with health-promoting bacteria and positively associated with pathogenic bacteria. Our findings will provide insight into how lifestyle factors that have not been fully explored to date such as stress may be associated with risk for CRC as a result of how stress perturbs the microbiota. If we determine that stress contributes to CRC risk via microbial perturbations, future bio-behavioral interventions that incorporate stress management and dietary/supplemental recommendations to promote mucosal health, and therefore reduce CRC risk, can be developed and implemented which could lead to diminished health care costs related to diagnosis and treatment and reduce CRC disparities between black and white women. In addition to providing valuable data, the proposed research project will also provide the opportunity for the additional training needed for Dr. Carson's development as an independently funded bio-behavioral cancer disparities researcher. Dr. Carson will engage in an intensive, structured training experience to develop expertise by completing the following: 1) Training in the recruitment of racially diverse clinical and community populations for bio-specimen and bio-banking research, 2) Obtaining hands-on and didactic training in bioinformatics techniques, and 3) Improving professional skills such as team science, networking, grant writing, mentoring, and high-impact publications. Under the guidance of an esteemed panel of mentors and collaborators and the high quality research and training environment that the University of Alabama at Birmingham offers, Dr. Carson's research and training experiences will make a significant contribution to the scientific community and Dr. Carson's overall career development.

 描述(申请人提供)：蒂凡尼·卡森博士是一名应用流行病学家，有研究黑人和白人女性健康差距的背景。卡森博士早期的研究重点是与饮食、体育活动、肥胖和相关健康结果相关的行为。最近，卡森博士专注于应用她的研究成果来更好地了解黑人和白人女性在癌症方面的差异。卡森博士的首要职业目标是成为一名独立资助的研究人员，并开发以证据为基础的生物行为干预措施，以减少癌症健康差距。为此，该申请提出了一项严格的研究项目和培训计划，重点是调查微生物区系作为黑人和白人女性结直肠癌(CRC)差异的新的潜在贡献者。结直肠癌是美国癌症死亡的第二大原因 占癌症死亡人数的9%。已知的结直肠癌危险因素包括年龄增加、男性、家族史、炎症性肠道疾病、2型糖尿病、饮酒、吸烟、缺乏体育活动、大量食用红肉和加工肉类、高脂肪饮食以及肥胖。在女性中，即使考虑到风险因素分布的差异，黑人女性患CRC的风险仍然比白人女性高48%。越来越多的研究表明，饮食对结直肠癌风险的影响是通过微生物区系介导的，饮食、生活方式和抗生素引起的微生物扰动可能导致结直肠癌和其他慢性病风险增加。压力是已被证明导致微生物区系改变的一个因素。我们的研究表明，黑人女性报告的压力水平为中等到高度，另外出版的文献表明，黑人女性报告的压力水平高于白人女性。这些观察结果导致了我们的假设，即与白人女性相比，由于压力水平更高，更多的黑人女性具有令人不安的微生物区系，这使得黑人女性患CRC的风险更大。在目前的方案中，我们计划采用病例对照研究设计来探索这一假设，比较以下组：1)来自UAB Kirklin诊所的患有CRC的黑人和白人女性，以及2)年龄匹配的无癌症的黑人和白人女性社区对照组。具体地说，我们将首先描述患有CRC的黑人和白人妇女的口腔和肠道微生物区系，并按种族进行比较，特别关注已知的与CRC呈正或负相关的微生物。因为所有病例都会有结直肠癌，我们假设微生物区系或其他已知的结直肠癌危险因素(如饮食)不存在显著的种族差异。相比之下，当我们在无癌症的黑人和白人女性社区对照中重复这项实验时，我们预计会观察到微生物区系中的种族差异，黑人女性的健康促进细菌比白人女性更少，而致病细菌更多，这会增加黑人女性患CRC的风险。我们预计，控制组中更大比例的黑人女性将拥有类似于结直肠癌参与者的微生物区系。此外，如果我们的假设得到支持，心理压力与促进健康的细菌呈负相关，与致病细菌呈正相关。我们的发现将为深入了解迄今尚未充分探索的生活方式因素(如压力)如何与结直肠癌风险相关，因为压力是如何扰乱微生物区系的。如果我们确定应激通过微生物扰动导致结直肠癌风险，未来可以开发和实施生物行为干预措施，包括应激管理和饮食/补充建议，以促进粘膜健康，从而降低结直肠癌风险，从而减少与诊断和治疗相关的医疗成本，并减少黑人和白人女性之间的结直肠癌差异。除了提供有价值的数据，拟议中的研究项目还将为卡森博士发展成为一名独立资助的生物行为癌症差异研究人员提供额外培训的机会。卡森博士将参加一次密集的、有组织的培训经验，以通过完成以下工作来发展专业知识：1)为生物标本和生物银行研究招募不同种族的临床和社区人口的培训；2)获得生物信息学技术的实践和教学培训；3)提高专业技能，如团队科学、网络、赠款撰写、指导和高影响力的出版物。在受人尊敬的导师和合作者小组的指导下，以及阿拉巴马大学伯明翰分校提供的高质量研究和培训环境下，卡森博士的研究和培训经验将为科学界和卡森博士的整体职业发展做出重大贡献。