Lifestyle Factors and Survival Outcomes for Colorectal Cancer Molecular Subtypes

结直肠癌分子亚型的生活方式因素和生存结果

• 批准号: 8424186
• 负责人: AMANDA IRENE PHIPPS
• 金额: $ 12.52万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-02-13 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8424186
• 关键词: Address; Advisory Committees; Alcohol consumption; Area; BRAF gene; Biological; Body mass index; Cancer Biology; Cancer Patient; Cancer Prognosis; Carcinoma; Characteristics; Classification; Clinical; Clinical Treatment; Clinical Trials; Collaborations; Colon Carcinoma; Colorectal; Colorectal Cancer; Complement; CpG Island Methylator Phenotype; CpG Islands; Data; Development; Diagnosis; Diagnostic; Disease; Disease-Free Survival; Drug usage; Educational Curriculum; Enrollment; Environment; Epidemiologic Methods; Epidemiologist; Epidemiology; Evaluation; Fred Hutchinson Cancer Research Center; Future; Goals; Grant; Heterogeneity; Home environment; Individual; Joints; Journals; K-Series Research Career Programs; KRAS2 gene; Knowledge; Laboratory Scientists; Malignant Neoplasms; Mentors; Mentorship; Methodology; Methylation; Microsatellite Instability; Molecular; Mutation; NCI Center for Cancer Research; Non-Steroidal Anti-Inflammatory Agents; North Central Cancer Treatment Group; Observational Study; Outcome; Outcomes Research; Pathology; Pathway interactions; Patients; Pharmacoepidemiology; Phase; Phenotype; Physical activity; Play; Population Study; Predictive Factor; Prognostic Factor; Public Health; Randomized Clinical Trials; Recurrence; Registries; Research; Research Activity; Research Personnel; Research Project Grants; Resources; Risk Factors; Role; Running; Science; Scientist; Seasons; Series; Smoking; Smoking History; Somatic Mutation; Source; Specialist; Staging; Teaching Materials; Testing; Training Activity; Translating; Tumor Markers; Universities; Vital Status; Washington; Work; adenoma; base; cancer diagnosis; cancer epidemiology; cancer risk; cancer therapy; career; career development; clinical epidemiology; clinical practice; clinically relevant; cohort; colon cancer family registry; design; disorder subtype; doctoral student; empowered; epidemiologic data; epidemiology study; experience; follow-up; interest; lifestyle factors; malignant breast neoplasm; mutant; oncology; outcome forecast; population based; pre-doctoral; prognostic; programs; randomized trial; skills; stem; tool; treatment trial; triple-negative invasive breast carcinoma; tumorigenesis; validation studies

DESCRIPTION (provided by applicant): The overarching goal motivating my research has been to characterize biological heterogeneity in cancer and its impact on cancer epidemiology. As an epidemiology doctoral student at the University of Washington (UW), I developed a research portfolio characterizing risk factors for triple-negative breast cancer - a poor prognosis poorly understood breast cancer subtype. Following my graduation from UW in 2010, my research transitioned from the study of breast cancer to the study of colorectal cancer (CRC), and from the study of cancer risk to the study of cancer survival. In extending my research to the study of CRC survival, the goal motivating my work has remained the same but my specific research interests have evolved to encompass areas in which I have not previously been involved. In particular, I have developed an interest in clinical epidemiology and in studies based in the clinical trial setting. The research and training activities proposed for this career development award will allow me to gain the skills, experience, and collaborations necessary to launch an independent academic career in cancer survival, and to transition my research into a more translational realm. Unifying my predoctoral, postdoctoral, and proposed research is an interest in the relationship between cancer biology and cancer epidemiology. Like breast cancer, CRC is a heterogeneous disease that can be classified into biologically distinct subtypes. Unlike breast cancer, however, molecularly-defined subtypes of CRC have not yet been widely characterized. Molecular classifications for CRC subtypes were recently proposed, using information on four tumor markers: microsatellite instability (MSI), CpG island methylation (CIMP), mutations in BRAF, and mutations in KRAS. Different combinations of these four markers are thought to reflect distinct pathways of CRC development. Biological distinctions between CRC subtypes defined by these markers also likely translate to differences in prognosis and prognostic factors, although such differences have not yet been well described. The research objectives of this proposal are to assess the prognostic significance of CRC molecular subtypes defined by joint MSI / CIMP / BRAF / KRAS status, and to assess the impact of modifiable lifestyle factors on clinical outcomes after CRC diagnosis for patients with these subtypes of disease. The ultimate goal of this research is to identify factors that will have clinical relevance in informing CRC survival. In pursuit of these research objectives, I will leverage data from two very rich but very different studies with which I have existing collaborations: the Seattle Colon Cancer Family Registry (S-CCFR) and a phase III randomized clinical trial of stage III colon cancer (N0147). Both studies are well annotated with epidemiologic data and information on MSI, CIMP, and BRAF and KRAS mutation status in CRC patients. Through the proposed research activities, I will use data from both studies to characterize differences in modifiable lifestyle factors (Aim 1a) and survival (Aim 1b) across four CRC subtypes defined by joint MSI / CIMP / BRAF / KRAS status. I will also use these data to assess the relationship between several lifestyle factors (e.g., smoking, alcohol consumption, physical activity) and survival in patients with these four subtypes of CRC (Aims 2-3). Conducting parallel analyses in an observational study (S-CCFR) and in a clinical trial (N0147) will provide opportunities for comparing and contrasting results across study settings with complementary strengths and limitations. This approach of parallel and complementary analyses will also provide me with experience in working with clinical outcomes data collected in different study settings and in working with clinical trials. In conducting the proposed research, will benefit from the rich resources and collaborative environment of the Fred Hutchinson Cancer Research Center (FHCRC). As one of the world's leading cancer research centers, the FHCRC is home to a large number of distinguished epidemiologists, clinical researchers, and laboratory scientists who can provide directed guidance. In particular, I will benefit from the mentorship of Dr. Polly Newcomb (primary mentor), who has considerable expertise in CRC epidemiology and observational studies of cancer survival and who is PI of the S-CCFR. I will also be mentored by Dr. Noel Weiss (co-mentor), who is a seasoned expert in epidemiologic methods and clinical epidemiology. For further guidance, I have enlisted the expertise of an external advisory committee, comprised of specialists in the conduct of oncology clinical trials (Dr. Steven Alberts, who is also the N0147 Study Chair), in the conduct of correlative science across study settings (Dr. Paul Limburg), in the epidemiology and treatment of CRC (Dr. Andrew Chan), and in CRC pathology (Dr. Christophe Rosty). To complement my research and further my career development, I will also work with Dr. Weiss to develop and implement materials for teaching a graduate-level epidemiologic methods course series. The hands-on experience and expertise gained through this project will be supplemented by formal coursework in outcomes research, pharmacoepidemiology, and clinical trial methodologies, and by regular research seminars offered through the FHCRC, the UW, and other programs. Both the FHCRC and the UW place particular emphasis on providing early career scientists with career development opportunities, offering formal mechanisms for mentoring, regular career development seminars, journal clubs, curriculum evaluation, and other networking resources. Thus, the environment of the FHCRC, and the closely affiliated UW, provides an excellent setting in which to launch my independent academic research career.

描述（由申请人提供）：激励我研究的首要目标是表征癌症的生物学异质性及其对癌症流行病学的影响。作为华盛顿大学（UW）的一名流行病学博士生，我开发了一个研究组合，描述了三阴性乳腺癌的危险因素，这是一种预后不佳的乳腺癌亚型。2010年从UW毕业后，我的研究从乳腺癌的研究转向了结直肠癌的研究，从癌症风险的研究转向了癌症生存的研究。在将我的研究扩展到CRC生存研究的过程中，激励我工作的目标保持不变，但我的具体研究兴趣已经发展到包括我以前没有参与的领域。特别是，我对临床流行病学和基础研究产生了兴趣