Dietary Calcium and Magnesium, Genetics, and Colorectal Adenoma

膳食钙和镁、遗传学和结直肠腺瘤

• 批准号: 7486129
• 负责人: QI DAI
• 金额: $ 56.21万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7486129
• 关键词: Accounting; Address; Applications Grants; Biological; Calcium; Cancer Etiology; Candidate Disease Gene; Case-Control Studies; Cessation of life; Clinical; Clinical Trials; Colonoscopy; Colorectal Adenoma; Colorectal Cancer; Colorectal Polyp; Data; Development; Diagnosis; Dietary Calcium; Enrollment; Epidemiologic Studies; Equilibrium; Evaluation; Genes; Genetic; Genetic Polymorphism; Genotype; Haplotypes; Homeostasis; Hyperplastic Polyp; Individual; Intake; Link; Magnesium; Molecular; N-(3,4,5-trichlorophenyl)succinimide; Nutrient; Nutritional; Pathway interactions; Pattern; Penetrance; Personal Satisfaction; Phase; Physiological; Polyps; Population; Prevention strategy; Regulation; Research Design; Resources; Risk; Sampling; Staging; Tennessee; Testing; Variant; Vitamin D; absorption; adenoma; base; fortification; gene interaction; genetic variant; good diet; novel; nutrition; prevent; protective effect; response

DESCRIPTION (provided by applicant): Project Summary: Results have been inconsistent on the protective effect of calcium and magensium intake on colorectal cancer and adenoma. We found very recently in the Tennessee Colorectal Polyp Study (TCPS; P50CA95103) that the associations between intake of calcium or magnesium and risk of colorectal adenoma and hyperplastic polyps may differ by the common Thr1482Ile polymorphism of the TRPM7 gene, a gene involved in calcium and magnesium re(absorption) and homeostasis. Our finding may partially explain the inconsistency in previous studies on calcium and magnesium. In addition, we found that the ratio of calcium to magnesium intake significantly interacted with the Thr1482Ile polymorphism in relation to both adenomatous and hyperplastic polyps. In response to PAR-07-377, we propose a clinical epidemiologic study, based on our promising data, to test several novel hypotheses regarding gene-nutrition interactions using data and biological samples collected as part of the TCPS, a large on-going molecular epidemiologic case-control study of colorectal adenoma. Specifically, we will 1) confirm our pilot finding in an independent set; and 2) conduct a two-phase study to evaluate the relationships between other polymorphisms in 14 candidate genes involved in magnesium and calcium (re)absorption, regulation and balance and risk of colorectal adenoma; and investigate whether the associations between intake of calcium and magnesium or the ratio of calcium to magnesium intake and risk of colorectal adenoma differs by the genotypes or haplotypes in the 14 genes. The first phase of the study will include 1200 cases and 2400 controls to comprehensively investigate promising polymorphisms and their interactions with nutrients. All promising variants will be re-evaluated in an independent set of 800 cases and 1600 controls to validate the identified associations or nutrient-gene interactions. The proposed two-phase study design will allow us to effectively address potential false positive findings (Type I error), one of the most serious concerns regarding association studies of low-penetrance genetic factors and will allow us to enhance the statistical power for evaluation of gene-gene and gene-nutrition interactions. The results from our study will help to identify people at a high risk of colorectal adenoma and to develop personalized strategies of dietary changes or nutritional fortication to prevent occurrence of colorectal adenoma, and, thus, colorectal cancer. In the general US population, 1 in 18 individuals will develop colorectal cancer over their lifetime and forty percent will die within five years of diagnosis, mainly due to diagnosis at a late stage. Therefore, development of primary preventive strategies for colorectal cancer is very critical. The results from our study will help to identify people at a high risk of colorectal adenoma and to develop personalized strategies to prevent occurrence of colorectal adenoma, and, thus, colorectal cancer through dietary changes or nutritional fortification.

描述（由申请人提供）：项目摘要：结果对钙和Magensium摄入对结直肠癌和腺瘤的保护作用不一致。我们最近在田纳西州结直息息肉研究（TCP; p50ca95103）中发现，钙或镁的摄入量与大肠腺瘤的风险与大植物腺瘤的风险与增生息肉之间的关联可能因TRPM7基因的常见Thr1482ile多态性而有所不同。镁RE（吸收）和稳态。我们的发现可能部分解释了先前关于钙和镁的研究的不一致。此外，我们发现，钙与镁摄入量的比率与腺瘤和增生性息肉相关的THR1482IL多态性显着相互作用。为了响应PAR-07-377，我们根据我们有希望的数据提出了一项临床流行病学研究，以使用TCP的一部分收集的数据和生物样品来检验几种有关基因 - 氮相互作用的新型假设，这是一个大型分子的一部分大肠腺瘤的流行病学病例对照研究。具体来说，我们将在独立组中确认我们的试点发现；和2）进行两阶段研究，以评估14个参与镁和钙（RE）吸收，调节以及结构性腺瘤的风险和风险的14个候选基因中其他多态性之间的关系；并研究钙与镁的摄入量或钙与镁摄入量的比率和结直肠腺瘤的风险是14个基因中的基因型或单倍型的不同。 该研究的第一阶段将包括1200例病例和2400例对照，以全面研究有希望的多态性及其与养分的相互作用。在独立的800例和1600个对照组中，将重新评估所有有希望的变体，以验证已识别的关联或营养基因相互作用。拟议的两阶段研究设计将使我们能够有效解决潜在的假阳性发现（I型错误），这是有关低渗透率遗传因素的关联研究的最严重关注之一，并使我们能够增强评估评估的统计能力基因 - 基因和基因 - 互动相互作用。我们研究的结果将有助于识别有结直肠腺瘤的高风险的人，并制定个性化的饮食变化或营养固化策略，以防止发生结直肠腺瘤的发生，从而导致结直肠癌。在美国普通人群中，十分之一的人将在其一生中患上大肠癌，而四十％的人将在诊断后的五年内死亡，这主要是由于晚期诊断。因此，制定大肠癌的主要预防策略非常关键。我们研究的结果将有助于鉴定有结直肠腺瘤的高风险的人，并制定个性化策略，以防止发生结直肠腺瘤的发生，从而通过饮食上的改变或营养强化来确定结直肠癌。