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: 8072083
• 负责人: QI DAI
• 金额: $ 43.63万
• 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 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8072083
• 关键词: Accounting; Address; Adenomatous Polyps; 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; Dietary Magnesium; Dietary Practices; Enrollment; Epidemiologic Studies; Epidemiology; Equilibrium; Evaluation; Genes; Genetic; Genetic Polymorphism; Genotype; Haplotypes; Homeostasis; Hyperplastic Polyp; Individual; Intake; Link; Magnesium; Molecular; Nutrient; Nutritional; Pathway interactions; Penetrance; Phase; Physiological; Polyps; Population; Prevention strategy; Regulation; Research Design; Resources; Risk; Sampling; Staging; Tennessee; Testing; Variant; Vitamin D; absorption; adenoma; base; calcium intake; fortification; gene interaction; genetic variant; good diet; high risk; 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）：项目总结：关于钙和镁摄入对结直肠癌和腺瘤的保护作用的结果不一致。我们最近在田纳西州结直肠息肉研究（TCPS; P50 CA 95103）中发现，钙或镁摄入量与结直肠腺瘤和增生性息肉风险之间的关系可能因TRPM 7基因的常见Thr 1482 Ile多态性而不同，TRPM 7基因是一种参与钙和镁再吸收和稳态的基因。我们的发现可能部分解释了以前对钙和镁研究的不一致性。此外，我们发现，钙镁摄入量的比例显着相互作用的Thr 1482 Ile多态性有关腺瘤性和增生性息肉。作为对PAR-07-377的回应，我们提出了一项临床流行病学研究，基于我们有希望的数据，使用作为TCPS（一项正在进行的大肠腺瘤大型分子流行病学病例对照研究）的一部分收集的数据和生物样本来检验关于基因-营养相互作用的几种新假设。具体来说，我们将1）在一个独立的集合中证实我们的初步发现; 2）进行一项两阶段研究，以评估参与镁和钙（再）吸收、调节和平衡的14个候选基因中的其他多态性与结直肠腺瘤风险之间的关系;并研究钙镁摄入量或钙镁摄入比例与结直肠癌风险之间的关系，腺瘤的不同之处在于14个基因的基因型或单倍型。 该研究的第一阶段将包括1200例病例和2400例对照，以全面调查有希望的多态性及其与营养素的相互作用。所有有希望的变异将在800例病例和1600例对照的独立组中重新评估，以验证所确定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地解决潜在的假阳性结果（I型错误），这是关于低突变遗传因素关联研究的最严重问题之一，并将使我们能够提高评估基因-基因和基因-营养相互作用的统计能力。我们的研究结果将有助于识别结直肠腺瘤的高风险人群，并制定个性化的饮食改变或营养强化策略，以预防结直肠腺瘤的发生，从而预防结直肠癌。在一般美国人群中，每18个人中就有1人会在其一生中患上结直肠癌，40%的人会在诊断后5年内死亡，主要是由于晚期诊断。因此，制定结直肠癌的一级预防策略非常关键。我们的研究结果将有助于识别结直肠腺瘤的高风险人群，并制定个性化的策略来预防结直肠腺瘤的发生，从而通过饮食改变或营养强化来预防结直肠癌。

项目成果

Blood magnesium, and the interaction with calcium, on the risk of high-grade prostate cancer.

血液镁以及与钙的相互作用，面临着高级前列腺癌的风险。

• DOI: 10.1371/journal.pone.0018237
• 发表时间: 2011-04-25
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Dai Q;Motley SS;Smith JA Jr;Concepcion R;Barocas D;Byerly S;Fowke JH
• 通讯作者: Fowke JH

Magnesium, vitamin D status and mortality: results from US National Health and Nutrition Examination Survey (NHANES) 2001 to 2006 and NHANES III.

• DOI: 10.1186/1741-7015-11-187
• 发表时间: 2013-08-27
• 期刊: BMC medicine
• 影响因子: 9.3
• 作者: Deng X;Song Y;Manson JE;Signorello LB;Zhang SM;Shrubsole MJ;Ness RM;Seidner DL;Dai Q
• 通讯作者: Dai Q

Genetic variation in SLC7A2 interacts with calcium and magnesium intakes in modulating the risk of colorectal polyps.

SLC7A2 的遗传变异与钙和镁的摄入量相互作用，调节结直肠息肉的风险。

• DOI: 10.1016/j.jnutbio.2017.04.016
• 发表时间: 2017
• 期刊: The Journal of nutritional biochemistry
• 作者: Sun,Pin;Zhu,Xiangzhu;Shrubsole,MarthaJ;Ness,ReidM;Hibler,ElizabethA;Cai,Qiuyin;Long,Jirong;Chen,Zhi;Li,Guoliang;Hou,Lifang;Smalley,WalterE;Edwards,ToddL;Giovannucci,Edward;Zheng,Wei;Dai,Qi
• 通讯作者: Dai,Qi