Accelerating Transdisciplinary Epidemiology of Colorectal Cancer

 描述（由申请人提供）：加速结直肠癌的跨学科流行病学概述肿瘤演变是受体细胞分子改变、宿主免疫、饮食、生活方式、微生物群和环境影响的异质过程。因此，我计划 采取跨学科的方法，整合分子水平的研究，人口水平的研究设计，以及环境，饮食和生活方式的评估，利用我独特的跨学科专业知识。我一直在发展分子病理流行病学（MPE）的跨学科领域，结合病理学和流行病学的综合优势。我将追求两个相互关联的协同主题：（1）结直肠癌（CRC）的MPE和（2）加速跨学科流行病学。在主题1中，我将在护士健康研究（NHS），NHS 2和卫生专业人员随访研究（HPFS）中整合2,500个CRC的肿瘤分子和免疫分析。我已经成功地建立了一个前所未有的高维度CRC数据库，包括长期暴露、肿瘤病理学、微生物、分子和免疫数据以及临床结果，以测试以下广泛的假设：（1.1）饮食、生活方式、环境和遗传因素通过分子、微生物和免疫亚型不同地影响CRC发病率。(1.2)CRC分子特征影响对CRC的免疫应答。(1.3)CRC分子和免疫状态影响患者的生存和对药物或可改变的饮食、生活方式或环境因素的反应。(1.4)CRC瘤内异质性的程度与较差的预后和特定的流行病学、临床和病理特征相关。我们将把我们的综合研究扩展到各种其他环境，以复制研究结果，并评估种族，社会经济和其他因素的潜在影响。该项目可以确定潜在的策略，以针对CRC预防和治疗的分子改变，免疫和微生物群。我的主题2计划是;（2.1）发展研究框架、分析设计和统计方法，以解决癌症的分子和病因异质性;（2.2）发展正在进行的国际MPE会议系列，以促进无缝的跨学科整合，目标是制定“STROBE-MPE指南”;（2.3）协同专家，构建“因果推理-MPE”和“MPE-健康传播研究”的跨学科整合模式。因此，我的目标是促进分子病理学和群体癌症科学的跨学科整合，并解决一个关键的未满足的需求，整合癌症免疫，肿瘤分子谱（包括微生物群和肿瘤内异质性），可修改的暴露，遗传学和CRC发病率和死亡的分析。我还试图解决跨学科流行病学的挑战，包括缺乏跨学科专家和培训计划，以及缺乏MPE的研究指南。我独特的资格和跨学科研究计划不仅可以在基于人群的规模上提供关于CRC病因学的新见解，还可以开发新的方法/框架和人群癌症科学的前沿。因此，我提出的研究可能会对未来的研究，临床实践和公共卫生产生重大影响。

 DESCRIPTION (provided by applicant): Accelerating Transdisciplinary Epidemiology of Colorectal Cancer Summary Tumor evolution is a heterogeneous process influenced by somatic molecular alterations, host immunity, diet, lifestyle, microbiota, and environment. Thus, I plan to take a transdisciplinary approach integrating molecular- level research, population-level study design, and assessment of environment, diet and lifestyle, utilizing my unique interdisciplinary expertise. I have been developing the transdisciplinary field of Molecular Pathological Epidemiology (MPE) with integrated strengths of both pathology and epidemiology. I will pursue two interconnecting synergistic Themes: (1) MPE of colorectal cancer (CRC) and (2) accelerating transdisciplinary epidemiology. In Theme 1, I will integrate tumor molecular and immunity analyses in 2,500 CRCs in the Nurses' Health Study (NHS), the NHS2 and the Health Professionals Follow-up Study (HPFS). I have successfully built an unprecedented high-dimensional CRC database on long-term exposures, tumor pathology, microbial, molecular and immunity data, and clinical outcome, to test the following broad-term hypotheses: (1.1) Dietary, lifestyle, environmental and genetic factors influence CRC incidence differentially by molecular, microbial and immunity subtypes. (1.2) CRC molecular features influence immune response to CRC. (1.3) CRC molecular and immunity status influences patient survival and response to drugs or modifiable dietary, lifestyle or environmental factors. (1.4) The degree of CRC intratumor heterogeneity is associated with worse prognosis and specific epidemiologic, clinical, and pathological features. We will extend our integrative research to various other settings to replicate findings and assess potential effect modifications by ethnic, socioeconomic and other factors. This project may identify potential strategies to target molecular alterations, immunity and microbiota for CRC prevention and therapy. My Theme 2 plans are; (2.1) to develop research frameworks, analysis designs and statistical methods, to address molecular and etiologic heterogeneity of cancer; (2.2) to grow the ongoing International MPE Meeting Series, to facilitate seamless transdisciplinary integration with a goal of making "the STROBE-MPE guidelines"; and (2.3) to synergize with experts and build new integrative transdisciplinary models, "causal inference-MPE" and "MPE-health communication research". Thus, I aim to promote transdisciplinary integration of molecular pathology and population cancer science, and to address a critical unmet need to integrate analyses of cancer immunity, tumor molecular profiles (including microbiota and intratumor heterogeneity), modifiable exposures, genetics, and CRC incidence and death. I also try to address challenges in transdisciplinary epidemiology, including paucity of interdisciplinary experts and training programs, as well as lack of research guidelines in MPE. My unique qualifications and transdisciplinary research program can not only provide new insights on CRC etiologies in a population-based scale, but also develop novel methods / frameworks, and frontiers of population cancer science. As such, my proposed research will likely have major impacts on future research, clinical practice and public health.