Obesity, sedentary behaviors, and diet quality for prevention and early detection of early-onset colorectal neoplasia

肥胖、久坐行为和饮食质量有助于预防和早期发现早发性结直肠肿瘤

基本信息

批准号：
10688157
负责人：
Yin Cao
金额：
$ 52.16万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10688157
关键词：
Adult African American Age American Cancer Society Archives Bioinformatics Biological Markers Blood Carcinoma Clinical Cohort Studies Collaborations Colon Colorectal Colorectal Cancer Communities Complement Data Decision Modeling Diabetes Mellitus Diagnostic Diet Early Diagnosis Early identification Endotoxemia Endotoxins Epidemiology Etiology Guidelines High Fat Diet Histology Immune response Incidence Inflammation Inflammatory Bowel Diseases Investigation Life Life Cycle Stages Life Style Life course epidemiology Link Longevity Measurement Mediating Meta-Analysis Modeling Molecular Neoplasms Nurses&apos Health Study Obesity Pathologic Pathway interactions Plasma Play Population Positioning Attribute Prevention Process Prospective cohort Proteomics Recommendation Relative Risks Reporting Research Personnel Research Priority Resources Risk Risk Factors Role Testing Time Unhealthy Diet Update adenoma biomarker discovery cancer diagnosis carcinogenesis circulating biomarkers colon carcinogenesis colon tumorigenesis colorectal cancer screening cost cost efficient early onset early onset colorectal cancer early onset colorectal neoplasm emerging adult gut dysbiosis improved inflammatory marker insight lifestyle data lifestyle factors microbial models and simulation multidisciplinary novel novel marker personalized screening prospective protein protein interaction screening screening guidelines sedentary sedentary lifestyle simulation systematic review systemic inflammatory response young adult

项目摘要

PROJECT SUMMARY/ABSTRACT The rising incidence in early-onset colorectal cancer (CRC diagnosed before 50), has resulted in updated American Cancer Society (ACS) guideline advising average-risk screening begin at age 45, rather than 50. Debates centered around the substantial cost and resources of adding 21 million adults at very low risk to the screening pool, and “further personalize screening strategies” was a priority. Identifying the contributors of the rising incidence are the first steps but thus far an unmet need. Lifestyle factors that preceded and mirrored the rapid rise of early-onset CRC, including obesity, prolong sitting, and poor diet, may play a critical role. Our preliminary data support the importance of obesity and sedentary behaviors and early-onset CRC are more likely to be processed from traditional adenoma-carcinoma sequence compared to CRC diagnosed after age 65. Therefore, investigation into risk factors for early-onset advanced adenoma, the major targets of screening, will illuminate insights of colorectal carcinogenesis at younger ages. Accumulating data suggest that microbial translocation/endotoxemia, which triggers subsequent inflammation and immune response, and augmented by above-mentioned lifestyle factors, might be an emerging pathway. We hypothesized that obesity, prolonged sitting, and poor diet quality increase risk of early-onset advanced adenoma through increasing endotoxemia and inflammation, and contribute to the rise of early-onset CRC. To test these hypotheses, we will leverage lifestyle data collected throughout life course in two well-characterized prospective cohort (Nurses’ Health Study II [NHSII]) and Southern Community Cohort Study (SCCS) with archived pre-diagnostic blood, complemented by decision modeling using the Microsimulation Screening Analysis‐Colon (MISCAN‐Colon), the model used to inform the ACS screening guideline. Specifically, we will first examine prospectively the associations between mid-adulthood and early-life obesity, sedentary behaviors, and diet quality and risk of early-onset advanced adenoma (Aim 1). We will then investigate into the independent and mediating role of pre-diagnostic plasma markers of endotoxemia and inflammation in early-onset neoplasia, leveraging a cost-efficient and reliable proteomic platform. Such profiling will also allow for untargeted discoveries of protein-protein interactions to identify novel networks/targets (Aim 2). Finally, we will conduct a meta-analysis to identify early-onset CRC specific risk factors and quantify the relative risks, and integrate these findings to the MISCAN-Colon to estimate the contributions of secular changes of lifestyle to the rise of early-onset CRC and to improve the simulations used to support the 2018 ACS screening guideline using early-onset CRC specific risk factors/estimates (Aim 3). Our established team, led by an early stage investigator focused on early-onset CRC, and leaders in epidemiology, bioinformatics, biomarker measurement and discoveries, and decision modeling, offers unparalleled expertise. This investigation will illuminate significant insights into the etiology of early-onset CRC and will be a significant step forward to optimal/personalized CRC screening among younger adults.

项目概要/摘要早发性结直肠癌（50 岁之前诊断出的结直肠癌）发病率不断上升，导致更新美国癌症协会 (ACS) 指南建议平均风险筛查从 45 岁开始，而不是 50 岁。争论的焦点是增加 2100 万风险极低的成年人，需要大量成本和资源。筛选池和“进一步个性化筛选策略”是当务之急。发病率上升是第一步，但迄今为止，生活方式因素尚未得到满足。早发性结直肠癌的迅速增加，包括肥胖、久坐和不良饮食，可能发挥着关键作用。初步数据支持肥胖和久坐行为的重要性，并且更有可能发生早发性结直肠癌与 65 岁后诊断的 CRC 相比，根据传统的腺瘤-癌序列进行处理。因此，作为筛查的主要目标，调查早发晚期腺瘤的危险因素将有助于阐明年轻时结肠直肠癌发生的见解。积累的数据表明微生物。易位/内毒素血症，引发随后的炎症和免疫反应，并通过上述生活方式因素，可能是导致肥胖持续时间延长的一个新途径。久坐和不良饮食质量会增加内毒素血症，从而增加早发晚期腺瘤的风险和炎症，并导致早发性结直肠癌的增加。为了检验这些假设，我们将利用这一点。在两个特征明确的前瞻性队列中收集整个生命过程的生活方式数据（护士健康研究 II [NHSII]）和南部社区队列研究（SCCS），使用存档的诊断前血液进行补充通过使用微观模拟筛选分析-Colon (MISCAN-Colon) 进行决策建模，该模型用于具体来说，我们将首先前瞻性地检查之间的关联。中年和早期肥胖、久坐行为、饮食质量和早发晚期的风险然后我们将研究诊断前血浆的独立和中介作用。早发性肿瘤中内毒素血症和炎症的标志物，利用具有成本效益且可靠的方法蛋白质组学平台也将允许非针对性地发现蛋白质-蛋白质相互作用。最后，我们将进行荟萃分析来识别早发性 CRC。特定风险因素并量化相对风险，并将这些发现整合到 MISCAN-Colon 中进行估计生活方式的长期变化对早发性结直肠癌的增加的贡献以及改进模拟用于支持 2018 年 ACS 筛查指南，使用早发 CRC 特定风险因素/估计（目标 3). 我们建立的团队由专注于早发性 CRC 的早期研究人员和领导者领导流行病学、生物信息学、生物标志物测量和发现以及决策建模，提供这项研究将揭示对早发性结直肠癌病因的重要见解。这将是在年轻人中实现最佳/个性化 CRC 筛查的重要一步。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Charting the path forward to combat gastrointestinal cancers.

规划对抗胃肠道癌症的前进道路。

DOI：
发表时间：
2024-03
期刊：
影响因子：
0
作者：
Oduyale, Oluseye;Cao, Yin
通讯作者：
Cao, Yin

Obesity and Gastrointestinal Cancer: A Life Course Perspective.

肥胖和胃肠癌：生命历程的视角。

DOI：
发表时间：
2023-05-01
期刊：
影响因子：
13.8
作者：
Shi, Mengyao;Cao, Yin
通讯作者：
Cao, Yin

Rising incidence of early-onset colorectal cancer - a call to action.

早发性结直肠癌发病率上升——呼吁采取行动。

DOI：
发表时间：
2021-04
期刊：
影响因子：
0
作者：
Akimoto, Naohiko;Ugai, Tomotaka;Zhong, Rong;Hamada, Tsuyoshi;Fujiyoshi, Kenji;Giannakis, Marios;Wu, Kana;Cao, Yin;Ng, Kimmie;Ogino, Shuji
通讯作者：
Ogino, Shuji

Circulating markers of microbial translocation and host response to bacteria with risk of colorectal cancer: a prospective, nested case-control study in men.

微生物易位的循环标志物和宿主对具有结直肠癌风险的细菌的反应：一项针对男性的前瞻性、巢式病例对照研究。

DOI：
发表时间：
2023-05
期刊：
影响因子：
11.1
作者：
Shi, Mengyao;Zong, Xiaoyu;Hur, Jinhee;Birmann, Brenda M;Martinez;Epeldegui, Marta;Chan, Andrew T;Giovannucci, Edward L;Cao, Yin
通讯作者：
Cao, Yin

Vitamin D and Early-Onset Colorectal Cancer-Rays of Hope?

维生素 D 和早发性结直肠癌——希望之光？