A Case-Control Study to Evaluate Broad-Spectrum Antibiotic use and High Birth Weight as Potential Risk Factors for Early-Onset Colorectal Cancer
一项病例对照研究,评估广谱抗生素的使用和高出生体重作为早发性结直肠癌的潜在危险因素
基本信息
- 批准号:10687185
- 负责人:
- 金额:$ 36.05万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-15 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:20 year oldAccountingAddressAdultAgeAge YearsAmendmentAnatomyAnimalsAntibioticsAnxietyBiologicalBiometryBirthBirth WeightCaliforniaCancer ControlCancer EtiologyCarcinogensCase SeriesCase/Control StudiesCessation of lifeCharacteristicsChemicalsChildColorectal CancerComputerized Medical RecordCountryDataDeveloped CountriesDevelopmentDiabetes MellitusDiagnosisDietDiseaseEnvironmental ExposureEpidemicEpidemiologistEpidemiologyExposure toFood ContaminationFoundationsFrightGastroenterologyHereditary Neoplastic SyndromesHigh birth weight infantHormonesHumanIncidenceIncomeIndividualInterruptionKnowledgeLate-Onset DisorderLife StyleLinkLiteratureMalignant NeoplasmsMolecularNested Case-Control StudyObesityPathologicPathway interactionsPharmacoepidemiologyPhysical activityPlayPositioning AttributePreventionPrevention strategyPrivate SectorPublic HealthPublic SectorQuality of lifeRaceResearch DesignRiskRisk FactorsRoleSample SizeSamplingSomatomedinsStudy SubjectSubgroupSymptomsSystemTestingUnited StatesWaterWeight Gainage groupcancer diagnosiscancer sitecarcinogenesiscohortcolorectal cancer riskdensityearly life exposureearly onsetearly onset colorectal cancerearly screeningearly-onset colorectal carcinogenesisethnic diversityexperiencegut dysbiosisgut microbiomeimprovedin uteroinsightmRNA Differential Displaysnovelpopulation basedprenatalpublic health interventionrisk predictionrisk prediction modelscreeningsedentary lifestylestem cellstrendyoung adult
项目摘要
Project Abstract
The incidence of colorectal cancer in young adults under age 50 (referred to as early onset colorectal cancer
[eoCRC]) has been rising by a striking 2% per year in the United States since the 1990s. Even more notably, a
significant increase in eoCRC is experienced by every 5-year age group from as young as age 20 years. The
accompanying human toll should not be understated considering the mirroring rise of deaths due to eoCRC,
and the loss in quality of life given that most eoCRC are diagnosed at advanced stages. Despite urgent needs
to interrupt this trajectory, factors responsible for the rise of eoCRC are unknown, rendering the development
of effective cancer control strategies difficult. This study seeks to shed light on eoCRC risk factors that may
contribute to the rising incidence of this disease, directly addressing Provocative Question1 from RFA-CA-20-
004: “What are the underlying causes of the unexplained rising incidence in early-onset cancers?” Evidence
suggests that eoCRC may be a distinct disease subset with differential key risk factors from late-onset CRC.
To date, studies that investigated eoCRC etiology remain sparse, and they mostly focused on the role of
established risk factors for late-onset CRC, such as obesity, diet and physical activities. There has been a
general lack of studies that evaluate the role of alternative risk factors such as those that involve gut dysbiosis
and early life exposures in eoCRC etiology. To fill this critical gap, we will test novel hypotheses on the roles of
broad-spectrum antibiotic use and high birth weight in eoCRC etiology. Use of broad-spectrum antibiotics
results in intense and long-lasting gut dysbiosis, which is strongly implicated in CRC carcinogenesis. Further,
animal studies and recent epidemiologic evidence supports the role of broad-spectrum antibiotics as CRC
carcinogens. High birth weight, likely reflecting altered in-utero programming of key hormone pathways such as
the insulin-like growth factor system and higher number of stem cells at risk for carcinogenesis, has been
linked to risk of other young-onset cancers and late-onset CRC. Further, both broad-spectrum antibiotic use
and high birth weight have been on the rise for decades preceding the rise of eoCRC. We will use a
population-based, nested case-control study design, including ~1,100 eoCRC cases diagnosed between 2009-
2021 at Kaiser Permanente Southern California (KPSC) to carry out the following Specific Aims: (SA1) Test
the hypothesis that greater exposure to broad-spectrum antibiotics increases risk of eoCRC; and (SA2)
Test the hypothesis that high birth weight increases risk of eoCRC. KPSC's unique strengths include
large sample size, comprehensive electronic medical records, long-term membership retention, and great
racial/ethnic diversity. At the completion of these aims, we expect to (1) offer new insights into the
carcinogenesis of eoCRC; (2) facilitate the development of eoCRC risk prediction models; (3) inform targeted
early screening strategies; and (3) inform novel prevention strategies to amend this devastating epidemic.
项目摘要
50岁以下年轻人的结直肠癌发病率(称为早发性结直肠癌
[eoCRC])自20世纪90年代以来,在美国每年以惊人的2%的速度增长。更值得注意的是,A
从20岁开始,每5岁年龄组的eoCRC显著增加。的
考虑到eoCRC导致的死亡人数也相应上升,
以及生活质量的损失,因为大多数eoCRC是在晚期诊断的。尽管迫切需要
为了中断这一轨迹,导致eoCRC上升的因素尚不清楚,
有效的癌症控制策略是困难的。这项研究旨在阐明eoCRC的风险因素,
导致这种疾病的发病率上升,直接解决RFA-CA-20中的挑衅性疾病1-
004:“早发性癌症发病率不明原因上升的根本原因是什么?”证据
表明eoCRC可能是一个不同的疾病亚群,与晚发型CRC具有不同的关键风险因素。
迄今为止,研究eoCRC病因的研究仍然很少,他们主要集中在以下方面的作用:
晚发性CRC的既定风险因素,如肥胖、饮食和体育活动。出现了
普遍缺乏评估替代风险因素(如涉及肠道生态失调的风险因素)作用的研究
和生命早期暴露在eoCRC病因学中。为了填补这一关键空白,我们将测试新的假设的作用,
广谱抗生素的使用和高出生体重在eoCRC病因中的作用。使用广谱抗生素
导致强烈和持久的肠道生态失调,这与CRC致癌作用密切相关。此外,本发明还
动物研究和最近的流行病学证据支持广谱抗生素作为CRC的作用
致癌物质。高出生体重,可能反映了关键激素途径的宫内编程改变,例如
胰岛素样生长因子系统和更多有致癌风险的干细胞已经被发现
与其他初发性癌症和迟发性CRC的风险相关。此外,广谱抗生素的使用
在eoCRC兴起之前的几十年里,高出生体重一直在上升。我们将使用一个
基于人群的巢式病例对照研究设计,包括2009年至2010年期间诊断的约1,100例eoCRC病例。
2021年在凯撒医疗机构南加州(KPSC)进行以下具体目标:(SA 1)测试
假设更多地暴露于广谱抗生素会增加eoCRC的风险;以及(SA 2)
检验高出生体重增加eoCRC风险的假设。KPSC的独特优势包括
大样本量,全面的电子病历,长期的会员保留,
种族/民族多样性。在完成这些目标时,我们希望(1)提供新的见解,
(2)促进eoCRC风险预测模型的开发;(3)告知靶向
早期筛查策略;(3)为新的预防策略提供信息,以改变这种毁灭性的流行病。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Chun R. Chao其他文献
Trastuzumab therapy and new-onset hypertension in adolescents and young adults with breast cancer
- DOI:
10.1007/s10549-025-07760-0 - 发表时间:
2025-06-27 - 期刊:
- 影响因子:3.000
- 作者:
Renata Abrahão;Kathryn J. Ruddy;Cecile A. Laurent;Jessica Chubak;Eric C. Haupt;Ann M. Brunson;Erin E. Hahn;Chun R. Chao;Lisa M. Moy;Ted Wun;Lawrence H. Kushi;Theresa H. M. Keegan;Candice A. M. Sauder - 通讯作者:
Candice A. M. Sauder
A pragmatic randomized trial to compare strategies for implementing primary HPV testing for routine cervical cancer screening in a large healthcare system
一项实用的随机试验,比较在大型医疗保健系统中实施常规宫颈癌筛查的初级 HPV 检测策略
- DOI:
10.1186/s13012-025-01432-9 - 发表时间:
2025-05-12 - 期刊:
- 影响因子:13.400
- 作者:
Chun R. Chao;Nancy Cannizzaro;Erin E. Hahn;Ernest Shen;Chunyi Hsu;Quyen Ngo-Metzger;Michael K. Gould;Corrine E. Munoz-Plaza;Michael H. Kanter;Patricia Wride;Lena H. Ajamian;Melissa Hodeib;Benjamin I. Broder;Ivette T. Curiel;Alicia Castaneda;Stephanie K. Ong;Krishnansu Tewari;Ramez N. Eskander;Devansu Tewari;Brian S. Mittman - 通讯作者:
Brian S. Mittman
History of Type 2 Diabetes and Risk of Non-Hodgkin Lymphoma and Multiple Myeloma: A Pooled Prospective Analysis
- DOI:
10.1182/blood-2024-199150 - 发表时间:
2024-11-05 - 期刊:
- 影响因子:
- 作者:
Andres Ardisson Korat;Emily L. Deubler;Kimberly A. Bertrand;Lauren R Teras;James V. Lacey;Alpa V. Patel;Bernard A. Rosner;Yu-Hsiang Shu;Charlie Zhong;Sophia S. Wang;Brenda M. Birmann;Chun R. Chao - 通讯作者:
Chun R. Chao
Characterization of the Tumor Microenvironment of Diagnostic Bone Marrow Core Biopsies from African American Multiple Myeloma Patients Using Imaging Mass Cytometry
- DOI:
10.1182/blood-2024-208818 - 发表时间:
2024-11-05 - 期刊:
- 影响因子:
- 作者:
Anthony Colombo;Esther Lam;Ben Falk;Anton Luis Villamejor;Amie Hwang;Jose Aparicio;Jia Yin Wan;Chun R. Chao;Mallory Bernstein;Ravi Vij;Mark Fiala;Pei Lin;Robert Z. Orlowski;Imran Siddiqi;David Conti;Akil Merchant;Wendy Cozen - 通讯作者:
Wendy Cozen
Survival Disparities Among Overweight and Obese Adolescent and Young Adult Patients with Acute Lymphoblastic Leukemia in a Large Integrated Healthcare System
- DOI:
10.1182/blood-2024-194050 - 发表时间:
2024-11-05 - 期刊:
- 影响因子:
- 作者:
Matthew Newman;Zimin Zhuang;Chun R. Chao;Robert Cooper - 通讯作者:
Robert Cooper
Chun R. Chao的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Chun R. Chao', 18)}}的其他基金
Effectiveness and Mechanisms of Multilevel Implementation Strategies to Improve Provider Recommendation and Advance HPV Vaccination: a Cluster Randomized Trial
改善提供者推荐和推进 HPV 疫苗接种的多层次实施策略的有效性和机制:整群随机试验
- 批准号:
10450821 - 财政年份:2021
- 资助金额:
$ 36.05万 - 项目类别:
Effectiveness and Mechanisms of Multilevel Implementation Strategies to Improve Provider Recommendation and Advance HPV Vaccination: a Cluster Randomized Trial
改善提供者推荐和推进 HPV 疫苗接种的多层次实施策略的有效性和机制:整群随机试验
- 批准号:
10650395 - 财政年份:2021
- 资助金额:
$ 36.05万 - 项目类别:
Effectiveness and Mechanisms of Multilevel Implementation Strategies to Improve Provider Recommendation and Advance HPV Vaccination: a Cluster Randomized Trial
改善提供者推荐和推进 HPV 疫苗接种的多层次实施策略的有效性和机制:整群随机试验
- 批准号:
10296607 - 财政年份:2021
- 资助金额:
$ 36.05万 - 项目类别:
A Case-Control Study to Evaluate Broad-Spectrum Antibiotic use and High Birth Weight as Potential Risk Factors for Early-Onset Colorectal Cancer
一项病例对照研究,评估广谱抗生素的使用和高出生体重作为早发性结直肠癌的潜在危险因素
- 批准号:
10304590 - 财政年份:2021
- 资助金额:
$ 36.05万 - 项目类别:
Follow-up care and preventive service use among survivors of adolescent and young adult cancer.
青少年和青年癌症幸存者的后续护理和预防服务使用。
- 批准号:
9178444 - 财政年份:2016
- 资助金额:
$ 36.05万 - 项目类别:
Prognostic Markers for HIV-Postive Diffuse Large B-Cell Lymphoma
HIV 阳性弥漫性大 B 细胞淋巴瘤的预后标志物
- 批准号:
7691293 - 财政年份:2008
- 资助金额:
$ 36.05万 - 项目类别:
Prognostic Markers for HIV-Postive Diffuse Large B-Cell Lymphoma
HIV 阳性弥漫性大 B 细胞淋巴瘤的预后标志物
- 批准号:
8120890 - 财政年份:2008
- 资助金额:
$ 36.05万 - 项目类别:
相似海外基金
Unraveling the Dynamics of International Accounting: Exploring the Impact of IFRS Adoption on Firms' Financial Reporting and Business Strategies
揭示国际会计的动态:探索采用 IFRS 对公司财务报告和业务战略的影响
- 批准号:
24K16488 - 财政年份:2024
- 资助金额:
$ 36.05万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Mighty Accounting - Accountancy Automation for 1-person limited companies.
Mighty Accounting - 1 人有限公司的会计自动化。
- 批准号:
10100360 - 财政年份:2024
- 资助金额:
$ 36.05万 - 项目类别:
Collaborative R&D
Accounting for the Fall of Silver? Western exchange banking practice, 1870-1910
白银下跌的原因是什么?
- 批准号:
24K04974 - 财政年份:2024
- 资助金额:
$ 36.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
A New Direction in Accounting Education for IT Human Resources
IT人力资源会计教育的新方向
- 批准号:
23K01686 - 财政年份:2023
- 资助金额:
$ 36.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
An empirical and theoretical study of the double-accounting system in 19th-century American and British public utility companies
19世纪美国和英国公用事业公司双重会计制度的实证和理论研究
- 批准号:
23K01692 - 财政年份:2023
- 资助金额:
$ 36.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
An Empirical Analysis of the Value Effect: An Accounting Viewpoint
价值效应的实证分析:会计观点
- 批准号:
23K01695 - 财政年份:2023
- 资助金额:
$ 36.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Accounting model for improving performance on the health and productivity management
提高健康和生产力管理绩效的会计模型
- 批准号:
23K01713 - 财政年份:2023
- 资助金额:
$ 36.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
CPS: Medium: Making Every Drop Count: Accounting for Spatiotemporal Variability of Water Needs for Proactive Scheduling of Variable Rate Irrigation Systems
CPS:中:让每一滴水都发挥作用:考虑用水需求的时空变化,主动调度可变速率灌溉系统
- 批准号:
2312319 - 财政年份:2023
- 资助金额:
$ 36.05万 - 项目类别:
Standard Grant
New Role of Not-for-Profit Entities and Their Accounting Standards to Be Unified
非营利实体的新角色及其会计准则将统一
- 批准号:
23K01715 - 财政年份:2023
- 资助金额:
$ 36.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Improving Age- and Cause-Specific Under-Five Mortality Rates (ACSU5MR) by Systematically Accounting Measurement Errors to Inform Child Survival Decision Making in Low Income Countries
通过系统地核算测量误差来改善特定年龄和特定原因的五岁以下死亡率 (ACSU5MR),为低收入国家的儿童生存决策提供信息
- 批准号:
10585388 - 财政年份:2023
- 资助金额:
$ 36.05万 - 项目类别: