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Colon Cancer Prevention Program Project Grant

结肠癌预防计划项目拨款

基本信息

批准号：
7683044
负责人：
M. Peter Lance
金额：
$ 423.65万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-03-01 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7683044
关键词：
Colon Cancer Prevention Program Project

项目摘要

Colorectal cancer is the second leading cause of cancer death in the U.S. The overall, long-term goal of our Program Project is to reduce the incidence, morbidity and mortality of colorectal cancer. To accomplish this goal, we seek to develop highly effective intervention strategies to prevent the recurrence of sporadic adenomatous polyps, and to define the fundamental epidemiologic, epigenetic and genetic mechanisms of polyp genesis and recurrence. Our Program Project consists of three highly interactive scientific research components as follows: 1. a phase III randomized, placebo-controlled, double-blind study of factorial design of the effect of celecoxib, a COX-2 inhibitor, and selenium, a nutritional supplement, and their combination on adenoma recurrence in 1600 participants. These agents were selected because of their different mechanistic effects on the colon carcinogenesis, well-documented activity in preclinical models, and safety profiles established in human studies. As secondary objectives, the influence of single nucleotide polymorphism variations will be analyzed in six genes for which there is evidence of genotypic effect modification of the celecoxib, aspirin or selenium interventions, or their toxicities 2. a pathologic, molecular, genetic and epidemiologic identification of a high risk colorectal adenoma phenotype, including an in-depth analysis of the serrated adenoma carcinogenesis pathway that ultimately will contribute to an improved comprehension of risk stratification, public health oriented screening, and chemoprevention strategies; and 3. an in-depth analysis of associations between diet and lifestyle factors that promote chronic hyperinsulinemia/insulin resistance (e.g. obesity, excess energy intake, glycemic index) and recurrent and high risk colorectal adenomas and carcinogenesis, including associations between candidate genotypes/haplotypes in genes involved in insulin production, clearance, and action as well as plasma biomarkers of insulin resistance. We will utilize frozen plasma, serum, peripheral blood leukocytes and archival polyp tissue obtained at multiple time points from more than 6,000 participants randomized into four colorectal polyp prevention trials (i.e., our Program Project's wheat bran fiber, ursodeoxycholic acid, and celecoxib/selenium trials and the NCI polyp prevention trial), as well as blood samples from over 2000 participants in the Colon Cancer Family Registry. To accomplish our goals, we have brought together a group of outstanding cancer researchers who have in most cases worked together for 10-15 years and have developed a highly integrated and interactive, hypothesis-driven research proposal with a strong likelihood of success that was crafted so that all Projects and Core Services within five large university medical centers and a research institute (Translational Genomics Research Institute - Phoenix) depend scientifically and operationally on each other.

结直肠癌是美国癌症死亡的第二大原因。我们项目的总体、长期目标是降低结直肠癌的发病率、发病率和死亡率。为了实现这一目标，我们寻求制定高效的干预策略来预防散发性腺瘤性息肉的复发，并确定息肉发生和复发的基本流行病学、表观遗传学和遗传机制。我们的项目包括以下三个高度互动的科研组成部分：1。一项III期随机、安慰剂对照、双盲研究，对1600名参与者进行了COX-2抑制剂塞来昔布和营养补充剂硒及其联合使用对腺瘤复发的影响进行了因子设计。选择这些药物是因为它们对结肠癌发生的不同机制作用，有充分证据的活性

项目成果

期刊论文数量（130）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A candidate gene study of folate-associated one carbon metabolism genes and colorectal cancer risk.

DOI：
10.1158/1055-9965.epi-10-0151
发表时间：
2010-07
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
0
作者：
Levine AJ;Figueiredo JC;Lee W;Conti DV;Kennedy K;Duggan DJ;Poynter JN;Campbell PT;Newcomb P;Martinez ME;Hopper JL;Le Marchand L;Baron JA;Limburg PJ;Ulrich CM;Haile RW
通讯作者：
Haile RW

Cyclooxygenase-2 expression and prostanoid biogenesis reflect clinical phenotype in human colorectal fibroblast strains.

Cyclooxygenase-2 表达和前列腺素生物合成反映了人结直肠成纤维细胞菌株的临床表型。

DOI：
发表时间：
2003
期刊：
Cancer research.
影响因子：
0
作者：
Zhu,Yingting;Hua,Ping;Lance,Peter
通讯作者：
Lance,Peter

Fecal bile acid concentrations in a subpopulation of the wheat bran fiber colon polyp trial.

麦麸纤维结肠息肉试验亚群的粪便胆汁酸浓度。

DOI：
发表时间：
2003
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
0
作者：
Alberts,DavidS;Einspahr,JanineG;Earnest,DavidL;Krutzsch,MaryF;Lin,Po;Hess,LisaM;Heddens,DavidK;Roe,DeniseJ;Martínez,MariaElena;Salen,Gerald;Batta,AK
通讯作者：
Batta,AK

Association between Cyclooxygenase expression and colorectal adenoma characteristics.

环加氧酶表达与结直肠腺瘤特征之间的关联。

DOI：
发表时间：
2003
期刊：
Cancer research.
影响因子：
0
作者：
Einspahr,JanineG;Krouse,RobertS;Yochim,JiMin;Danenberg,PeterV;Danenberg,KathleenD;Bhattacharyya,AchyutK;Martinez,MariaE;Alberts,DavidS
通讯作者：
Alberts,DavidS

Biomarker intermediate endpoints and cancer prevention.

生物标志物中间终点和癌症预防。