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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.

项目总结/文摘

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）

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？

DOI：
10.1053/j.gastro.2023.08.002
发表时间：
2023
期刊：
Gastroenterology
影响因子：
29.4
作者：
Cao,Yin;Chan,AndrewT
通讯作者：
Chan,AndrewT

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

DOI：
10.1038/s41571-020-00445-1
发表时间：
2021-04
期刊：
Nature reviews. Clinical oncology
影响因子：
0
作者：
Akimoto N;Ugai T;Zhong R;Hamada T;Fujiyoshi K;Giannakis M;Wu K;Cao Y;Ng K;Ogino S
通讯作者：
Ogino S

Obesity and Gastrointestinal Cancer: A Life Course Perspective.

肥胖和胃肠癌：生命历程的视角。

DOI：
10.1001/jamanetworkopen.2023.9921
发表时间：
2023
期刊：
JAMA network open
影响因子：
13.8
作者：
Shi,Mengyao;Cao,Yin
通讯作者：
Cao,Yin

Alcohol Drinking Without Meals Is Associated With Risk of Gastrointestinal Cancers, Including Early-Onset Cases.

不进餐饮酒与胃肠道癌症（包括早发病例）的风险相关。

DOI：
10.1053/j.gastro.2023.11.012
发表时间：
2024
期刊：
Gastroenterology
影响因子：
29.4
作者：
Shi,Mengyao;Ahmedin,NadiaJ;Zong,Xiaoyu;Yilmaz,ӦmerH;Bishehsari,Faraz;Cao,Yin
通讯作者：
Cao,Yin

Elucidating the Drivers for the Rising Incidence of Early-Onset Colorectal Cancer: How Ecologic Studies Could Help and What Is Next.

阐明早发性结直肠癌发病率上升的驱动因素：生态学研究如何提供帮助以及下一步。