Nutritional and Genetic Markers of Breast Cancer
乳腺癌的营养和遗传标志物
基本信息
- 批准号:7463655
- 负责人:
- 金额:$ 28.26万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2005
- 资助国家:美国
- 起止时间:2005-09-28 至 2011-07-31
- 项目状态:已结题
- 来源:
- 关键词:14q32.317p11.218p11.3219q13.21p221p36.31q4321q22.322q11.216p127q36.1AffectAlcohol consumptionAlcoholsAmino AcidsAnabolismAntioxidantsArchivesArtsAspirinBase Excision RepairsBiological AssayBiological MarkersBloodBlood specimenCandidate Disease GeneCarbonCardiovascular DiseasesCase-Control StudiesCatalytic DomainCatechol EstrogensCatechol O-MethyltransferaseClassCollectionComplementComplement component C1CysteineDNADNA Double Strand BreakDNA MethylationDNA RepairDNA Repair GeneDNA biosynthesisDNA chemical synthesisDataDevelopmentDocumentationEnzymesEtiologyExcision RepairFolateFolch-Pi apoproteinFolic Acid DeficiencyFundingGAG GeneGCLC geneGCLM geneGenesGeneticGenetic MarkersGenetic PolymorphismGenetic VariationGenotypeGlutamate-Cysteine LigaseGlutathioneGlycine HydroxymethyltransferaseHaplotypesHeartHomocysteineHomocystineIndividualInstitutesIntakeInvestigationLengthLife StyleLungMTHFR geneMalignant NeoplasmsMedicalMetabolismMethionineMethylationMethylenetetrahydrofolate reductase (NADPH)Methyltransferase GeneMyelin Proteolipid ProteinNational Cancer InstituteNumbersNutrientNutritionalParticipantPathway interactionsPlasmaPrevention strategyPrimary PreventionProspective StudiesPublic HealthPublishingPyridoxal PhosphateRateRecommendationResearch PersonnelResourcesRiskRoentgen RaysRoleSLC19A1 geneSample SizeStatistical MethodsStructureSupplementationTYMS geneTandem Repeat SequencesThymidylate SynthaseUntranslated RegionsVariantVitamin B 12Vitamin B ComplexVitamin B6Vitamin EVitaminsWomanWomen&aposs HealthXRCC1 geneXRCC2 geneXRCC3 genebasecancer riskchromosome 5q losscohortcostdesignfollow-upgenotyping technologyhomologous recombinationmalignant breast neoplasmmethionine synthase reductasemethyl groupnovelnutrient blood levelpreventprogramsprospectiverecombinational repairrepaired
项目摘要
We propose to conduct a prospective study of nutritional biomarkers and corresponding gene variants
involved in one-carbon metabolism¿and their interactive effects¿on breast cancer risk in the Women's
Health Study (WHS). A total of 1,100 incident cases of breast cancer will be identified and confirmed
among 28,345 participants with archived baseline blood specimens. We will assay five nutritional
biomarkers (i.e. plasma folate, vitamins B6 and B12, cysteine, and homocysteine). Applying state-of-the-
art genotyping technology and statistical methods, we will evaluate functional variants and determine
the structure ofhaplotypes in twelve relevant candidate genes. These genes will include glutamate-
cysteine ligase (GCLC [catalytic subunit] and GCLM[regulatory subunif]), folate-metabolizing genes
(reducedfolate carrier-1[RFC], 5,10-methylene-tetrahydrofolate reductase [MTHFR], methionine
synthase [MTR], methionine synthase reductase [MTRR], serine hydroxymethyltransferase [SHMT1],
and thymidylate synthase [TYMS]), catechol-O-methyltransferase (COMT), and DNA repair genes (X-
ray repair cross complementing [XRCC]-1, 2, and 3). There are at least three interrelated pathways by
which these markers may be associated with breast cancer risk. First, folate and vitamin B12 affect
methyl group availability and may thus prevent abnormal DNA methylation. Second, folate and vitamins
B6 and B12 influence DNA synthesis and repair. Third, cysteine is the key amino acid in the synthesis of
glutathione (GSH), an important intracellular antioxidant and detoxifying agent. GCLC and GCLM genes
encode a rate-limiting enzyme for GSH biosynthesis from cysteine. Available data also suggest that
folate interacts with alcohol intake to affect breast cancer risk. However, no published data have
evaluated whether GCLC, GCLM, RFC, MTR, MTRR, SHMT1, and TYMS polymorphisms affect breast
cancer risk. Findings from this study will help provide a basis for public health recommendations
regarding optimal levels of folate and B vitamin intakes, suggest new prevention strategies, and identify
high-risk individuals. Several unique features of the WHS, including its prospective design, large sample
size, long duration, high follow-up rates, availability of stored blood specimens, comprehensive
covariate information, and cost efficiency, make this cohort a valuable and exceptional resource for the
etiologic investigation of breast cancer.
我们建议对营养生物标记物和相应的基因变异进行前瞻性研究。
参与单碳代谢及其交互作用对女性乳腺癌风险的影响
健康研究(WHS)。将确定和确认总共1100例乳腺癌病例
在28345名有存档的基线血液样本的参与者中。我们将分析五种营养成分
生物标志物(即血浆叶酸、维生素B6和B12、半胱氨酸和同型半胱氨酸)。应用最新情况-
ART基因分型技术和统计方法,我们将评估功能变异并确定
12个相关候选基因的单倍型结构。这些基因将包括谷氨酸-
半胱氨酸连接酶(GCLC[催化亚基]和GCLM[调节亚单位]),叶酸代谢基因
(还原叶酸载体-1[RFC],5,10-亚甲基四氢叶酸还原酶[MTHFR],蛋氨酸
合酶[MTR]、蛋氨酸合成酶还原酶[MTRR]、丝氨酸羟甲基转移酶[SHMT1]、
和胸苷合成酶[TYMS])、儿茶酚-O-甲基转移酶(COMT)和DNA修复基因(X-
射线修复交叉互补[XRCC]-1、2和3)。至少有三条相互关联的路径
这些标记物可能与乳腺癌风险有关。首先,叶酸和维生素B12会影响
甲基的可用性,因此可以防止异常的DNA甲基化。第二,叶酸和维生素
B6和B12影响DNA的合成和修复。第三,半胱氨酸是合成半胱氨酸的关键氨基酸
谷胱甘肽(GSH),重要的细胞内抗氧化剂和解毒剂。Gclc和Gclm基因
编码半胱氨酸生物合成谷胱甘肽的限速酶。现有数据还表明,
叶酸与酒精摄入量相互作用,影响患乳腺癌的风险。然而,没有已发布的数据显示
评估GCLC、GCLM、RFC、MTR、MTRR、SHMT1和TYMS基因多态是否影响乳房
癌症风险。这项研究的发现将有助于为公共卫生建议提供基础
关于叶酸和维生素B的最佳摄入量,建议新的预防策略,并确定
高危人群。WHS的几个独特特征,包括其前瞻性设计、大样本
大小、持续时间长、随访率高、可获得储存的血液样本、全面
协变量信息和成本效率,使该队列成为
乳腺癌的病因学调查。
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)
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SHUMIN ZHANG其他文献
SHUMIN ZHANG的其他文献
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{{ truncateString('SHUMIN ZHANG', 18)}}的其他基金
Estrogen and Progesterone-related Gene Variants and Colorectal Cancer Risk
雌激素和孕激素相关基因变异与结直肠癌风险
- 批准号:
7136486 - 财政年份:2006
- 资助金额:
$ 28.26万 - 项目类别:
Estrogen and Progesterone-related Gene Variants and Colorectal Cancer Risk
雌激素和孕激素相关基因变异与结直肠癌风险
- 批准号:
7275969 - 财政年份:2006
- 资助金额:
$ 28.26万 - 项目类别:
Estrogen and Progesterone-related Gene Variants and Colorectal Cancer Risk
雌激素和孕激素相关基因变异与结直肠癌风险
- 批准号:
7666841 - 财政年份:2006
- 资助金额:
$ 28.26万 - 项目类别:
Estrogen and Progesterone-related Gene Variants and Colorectal Cancer Risk
雌激素和孕激素相关基因变异与结直肠癌风险
- 批准号:
7488912 - 财政年份:2006
- 资助金额:
$ 28.26万 - 项目类别:
Nutritional and Genetic Markers of Breast Cancer
乳腺癌的营养和遗传标志物
- 批准号:
7126513 - 财政年份:2005
- 资助金额:
$ 28.26万 - 项目类别:
Nutritional and Genetic Markers of Breast Cancer
乳腺癌的营养和遗传标志物
- 批准号:
6985866 - 财政年份:2005
- 资助金额:
$ 28.26万 - 项目类别:
Nutritional and Genetic Markers of Breast Cancer
乳腺癌的营养和遗传标志物
- 批准号:
7250218 - 财政年份:2005
- 资助金额:
$ 28.26万 - 项目类别:
Diet, Hormone Replacement Therapy and Breast Cancer
饮食、激素替代疗法和乳腺癌
- 批准号:
7114382 - 财政年份:2003
- 资助金额:
$ 28.26万 - 项目类别:
Diet, Hormone Replacement Therapy and Breast Cancer
饮食、激素替代疗法和乳腺癌
- 批准号:
6790035 - 财政年份:2003
- 资助金额:
$ 28.26万 - 项目类别:
Diet, Hormone Replacement Therapy and Breast Cancer
饮食、激素替代疗法和乳腺癌
- 批准号:
6611980 - 财政年份:2003
- 资助金额:
$ 28.26万 - 项目类别:
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