DIET, HORMONES, AND RISK OF COLORECTAL CANCER

饮食、激素和结直肠癌的风险

基本信息

  • 批准号:
    7630028
  • 负责人:
  • 金额:
    $ 82.22万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
  • 资助国家:
    美国
  • 起止时间:
  • 项目状态:
    未结题

项目摘要

Colorectal cancer is the second leading cause of cancer death in the United States. Without preventive actions, approximately 6% of Americans will develop this malignancy during their lifetime. In the past several decades, there have been major developments in our understanding of three pathogenic pathways for colorectal carcinogenesis: DNA methylation aberrations, which affect gene expression and genomic stability, insulin and insulin-like growth factor (IGF) signaling, which influences cell proliferation and apoptosis, and inflammation. Many of the proposed modifiable factors for colorectal cancer (low intakes of folate, vitamin B-6 and vitamin B-12, high alcohol intake, excess body weight, sedentary lifestyle, calcium intake and vitamin D levels, and non-use of aspirin) may operate through these pathways. We propose to examine prospectively and extensively how these modifiable factors may influence colorectal cancer risk operating through these three pathways. We will utilize data from the Nurses' Health Study, a large ongoing prospective study of women. We will study relevant exposures utilizing (1) multiple questionnaires accumulated over 30 years to assess the influence of long-term exposures including diet, (2) nutrient and hormonal biomarkers, and (3) genetic factors relevant to the pathways of interest. These exposures and genetic factors will be examined in relation to various endpoints including (1) total colorectal cancer incidence, (2) specific molecular alterations in colorectal cancer (including CpG island methylation, loss of expression of hMLHt, O6-methylguanine-DNA methyltransferase, p 16K and p27, and overexpression ofphospho-Akt and COX-2), and (3) survival from colorectal cancer following a curative resection of this cancer, after accounting for know prognostic factors for this disease. By better understanding underlying mechanisms, dose-response relations, inter-relations among factors acting in similar pathways (e.g. folate and vitamin B-6, insulin and IGF-1), variation in response due to genetic susceptibility, and specificity in associations to specific tumor markers which enhances the case for causality, we can solidify and refine recommendations aimed at reducing the incidence and mortality from this largely preventable cancer.
结直肠癌是美国癌症死亡的第二大原因。如果不采取预防措施, 大约6%的美国人在他们的一生中会发展这种恶性肿瘤。在过去的几十年里, 在我们对结直肠癌发生的三种致病途径的理解方面取得了重大进展:DNA 甲基化畸变,影响基因表达和基因组稳定性,胰岛素和胰岛素样生长因子(IGF) 信号传导,其影响细胞增殖和凋亡以及炎症。许多提议的可修改因素 对于结肠直肠癌(叶酸、维生素B-6和维生素B-12的低摄入,高酒精摄入,超重, 久坐不动的生活方式、钙摄入量和维生素D水平以及不使用阿司匹林)可能通过这些途径起作用。我们 我建议前瞻性地广泛研究这些可变因素如何影响结直肠癌风险 通过这三种途径。我们将利用护士健康研究的数据,这是一项正在进行的大型前瞻性研究 女人的研究。我们将利用(1)30年来积累的多份问卷调查来研究相关暴露, 评估长期暴露的影响,包括饮食,(2)营养和激素生物标志物,和(3)遗传因素 与感兴趣的途径相关。这些暴露和遗传因素将与各种终点相关 包括(1)总结直肠癌发病率,(2)结直肠癌中的特异性分子改变(包括CpG 岛甲基化,hMLHt、O 6-甲基鸟嘌呤-DNA甲基转移酶、p16 K和p27表达缺失,以及 磷酸化Akt和考克斯-2的过度表达),和(3)结肠直肠癌根治性切除后的存活率。 癌症,在考虑了这种疾病的已知预后因素后。通过更好地理解潜在的机制, 剂量-反应关系,在类似途径中起作用的因素之间的相互关系(例如叶酸和维生素B-6,胰岛素和 IGF-1),由于遗传易感性引起的反应变化,以及与特定肿瘤标志物相关的特异性, 加强因果关系的情况下,我们可以巩固和完善旨在降低发病率和死亡率的建议, 这种癌症在很大程度上是可以预防的。

项目成果

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EDWARD GIOVANNUCCI其他文献

EDWARD GIOVANNUCCI的其他文献

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{{ truncateString('EDWARD GIOVANNUCCI', 18)}}的其他基金

Decoding mechanisms underlying metabolic dysregulation in obesity and digestive cancer risk
肥胖和消化道癌症风险中代谢失调的解码机制
  • 批准号:
    10504203
  • 财政年份:
    2022
  • 资助金额:
    $ 82.22万
  • 项目类别:
Decoding mechanisms underlying metabolic dysregulation in obesity and digestive cancer risk
肥胖和消化道癌症风险中代谢失调的解码机制
  • 批准号:
    10707361
  • 财政年份:
    2022
  • 资助金额:
    $ 82.22万
  • 项目类别:
Association between pre-diagnosis hepatic fat infiltration and risk of liver metastasis and mortality in a large cohort of stage I-III colorectal cancer survivors
大量 I-III 期结直肠癌幸存者中诊断前肝脂肪浸润与肝转移风险和死亡率之间的关联
  • 批准号:
    10295142
  • 财政年份:
    2022
  • 资助金额:
    $ 82.22万
  • 项目类别:
Association between pre-diagnosis hepatic fat infiltration and risk of liver metastasis and mortality in a large cohort of stage I-III colorectal cancer survivors
大量 I-III 期结直肠癌幸存者中诊断前肝脂肪浸润与肝转移风险和死亡率之间的关联
  • 批准号:
    10709469
  • 财政年份:
    2022
  • 资助金额:
    $ 82.22万
  • 项目类别:
Impact of screening and diagnostic intensity on the study of prostate cancer epidemiology
筛查和诊断强度对前列腺癌流行病学研究的影响
  • 批准号:
    9811066
  • 财政年份:
    2019
  • 资助金额:
    $ 82.22万
  • 项目类别:
Colorectal Cancer
结直肠癌
  • 批准号:
    7786694
  • 财政年份:
    2010
  • 资助金额:
    $ 82.22万
  • 项目类别:
Energy Balance-Related Hormones & Prostate Cancer Incidence & Progression
能量平衡相关激素
  • 批准号:
    8138667
  • 财政年份:
    2008
  • 资助金额:
    $ 82.22万
  • 项目类别:
Energy Balance-Related Hormones & Prostate Cancer Incidence & Progression
能量平衡相关激素
  • 批准号:
    8301690
  • 财政年份:
    2008
  • 资助金额:
    $ 82.22万
  • 项目类别:
Energy Balance-Related Hormones & Prostate Cancer Incidence & Progression
能量平衡相关激素
  • 批准号:
    7693712
  • 财政年份:
    2008
  • 资助金额:
    $ 82.22万
  • 项目类别:
A Prospective Study of Diet and Prostate Cancer
饮食与前列腺癌的前瞻性研究
  • 批准号:
    7191213
  • 财政年份:
    2006
  • 资助金额:
    $ 82.22万
  • 项目类别:

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