Early Infant Feeding and Epigenetic Modification in Tumor Suppressor Genes

早期婴儿喂养和肿瘤抑制基因的表观遗传修饰

基本信息

批准号：
7943040
负责人：
ANNE MEREWOOD
金额：
$ 8.37万
依托单位：
BOSTON MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-29 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7943040
关键词：
Aberrant DNA Methylation Academy Acute Lymphocytic Leukemia Acute Myelocytic Leukemia Affect American Biological Birth Blood specimen Breast Feeding Candidate Disease Gene Child Childhood Childhood Acute Lymphocytic Leukemia Childhood Leukemia Cohort Studies DNA DNA Methylation Data Development Diet Dietary Component Dietary Intervention Enrollment Epigenetic Process Event Exclusive Breastfeeding Exposure to Food Funding Gene Expression Genes Goals Health Human Human Milk Immune system Individual Infant Infant formula Life Life Cycle Stages Link Malignant Childhood Neoplasm Malignant Neoplasms Mediating Methods Methylation Modification Molecular Newborn Infant Non-Human Protein Pathway interactions Pattern Pediatrics Peripheral Blood Lymphocyte Pharmaceutical Preparations Policy Making Population Pregnancy Prevention strategy Research Design Review Literature Risk Source Time Tumor Suppressor Genes United States Agency for Healthcare Research and Quality assault base cancer prevention cohort critical period design early childhood feeding genome wide association study genome-wide genome-wide analysis infancy infant nutrition nutrition prevent promoter public health relevance response

项目摘要

* DESCRIPTION (provided by applicant): Diet is known to impact DNA methylation, however, little is know about which dietary components are linked to cancer prevention. Human milk is the optimal and evolutionarily designed source of human infant nutrition; the American Academy of Pediatrics recommends that infants receive only human milk for the first 6 months of life. Breastfeeding is associated with reduced risk of childhood cancers including acute lymphoblastic leukemia. Levels of key dietary components known to affect methylation differ in human milk and infant formula, and accordingly, in infants fed human milk or formula. Goals: 1) To assess the effect of early feeding on aberrant methylation of 40 tumor suppressor genes in 100 infants (50 exclusively breastfed infants, and 50 exclusively formula fed infants) at 4 months. 2) To perform an exploratory genome-wide analysis of DNA from 10 infants who were exclusively breastfed for 4 months, compared with 10 exclusively formula fed infants, using methylation microarrays interrogating 18,000 gene promoters. Research Design and Methods: We will enroll 100 newborns and obtain blood samples at birth and 4 months, using infants already being enrolled in a funded cohort study. DNA from peripheral blood lymphocytes of infants who breastfeed exclusively for 4 months will be compared with those who formula feed only for 4 months. The primary analysis will be via methylation-specific real-time PCR for promoter methylation in 40 tumor suppressor genes associated with cancer, including childhood leukemia. Statistically significant differences in promoter methylation profiles will be assessed. The percent of tumor suppressor genes substantially methylated will be quantified in the two populations. Significance: Given that methylation is a potentially reversible DNA change, detecting a potential molecular link between early methylation changes, infant feeding, and childhood cancer development would have major implications for cancer prevention strategies. 1 PUBLIC HEALTH RELEVANCE: An association exists between breastfeeding and reduced risk of childhood leukemia, but no causal pathway has been determined. Levels of key dietary components known to affect methylation differ in human milk and infant formula. The present application will assess the effect of exclusive breastfeeding versus exclusive formula feeding on aberrant methylation of 40 tumor suppressor genes in 100, 4-month old infants, and will perform an exploratory genome-wide analysis of DNA from 20 infants using methylation microarrays interrogating 18,000 gene promoters. 1

* 描述（由申请人提供）：众所周知，饮食会影响DNA甲基化，但是，对哪些饮食成分与预防癌症有关。人牛奶是人类婴儿营养的最佳和进化设计的来源。美国儿科学会建议婴儿在生命的头六个月中仅接受人奶。母乳喂养与包括急性淋巴细胞白血病在内的儿童癌症风险降低有关。已知影响甲基化的关键饮食成分水平在人牛奶和婴儿配方奶粉中以及饲养人牛奶或配方奶粉的婴儿中有所不同。目标：1）评估100名婴儿（50只母乳喂养的婴儿和50个专门喂养婴儿）的早期进食对40个肿瘤抑制基因异常甲基化的影响。 2）使用甲基化微阵列询问18,000个基因启动子的甲基化微阵列，对10个专门母乳喂养的婴儿进行了4个月的10个婴儿的DNA进行探索性基因组分析。研究设计和方法：我们将使用已经在资助的队列研究中注册的婴儿在出生时和4个月的出生时和4个月接受血液样本。仅母乳喂养的婴儿外周血淋巴细胞的DNA将与仅喂养4个月的配方奶粉的婴儿进行比较。主要分析将通过甲基化特异性实时PCR进行，用于40种与癌症相关的肿瘤抑制基因（包括儿童白血病）的启动子甲基化。将评估启动子甲基化谱的统计学上显着差异。在两个种群中，将定量甲基化的肿瘤抑制基因百分比。意义：鉴于甲基化是一种可能可逆的DNA变化，检测到早期甲基化变化，婴儿喂养和儿童癌症发展之间的潜在分子联系将对癌症预防策略产生重大影响。 1 公共卫生相关性：母乳喂养与儿童白血病风险降低之间存在关联，但尚未确定因果途径。已知影响甲基化的关键饮食成分水平在人牛奶和婴儿配方中有所不同。本应用将评估排他性母乳喂养与排他性配方对100个4个月大婴儿40个肿瘤抑制基因异常的甲基化的影响，并将使用甲基化微阵列审查18,000个基因启动子对20个婴儿的DNA进行探索性基因组分析。 1