Influence of Dietary Pattern and Race on Metabolic and Epigenetic Alterations Associated with Cancer Development

饮食模式和种族对与癌症发展相关的代谢和表观遗传改变的影响

• 批准号: 10271245
• 负责人: Fayth Miles
• 金额: $ 12.04万
• 依托单位: LOMA LINDA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-25 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10271245
• 关键词: African; African American; Animal Feed; Animals; Anti-Inflammatory Agents; Behavior; Behavioral; Bioinformatics; Biological Markers; Biomarker of Dietary Intake; Blood specimen; Cancer Biology; Cancer Prevention Intervention; Carotenoids; Caucasians; Choline; Chronic; Code; Cohort Studies; Colorectal; Consumption; CpG Islands; DNA; Data; Development; Diet; Dietary Practices; Edible Plants; Educational workshop; Enzymes; Epidemiology; Epigenetic Process; Etiology; Experimental Nutrition; Familiarity; Folic Acid; Food; Fostering; Funding; Gastrointestinal tract structure; Genes; Genetic; Genome Stability; Genomics; Grant; Health; Hypermethylation; Incidence; Inflammation; Inflammatory; Inflammatory Response; Isoflavones; Lead; Link; Malignant Neoplasms; Malignant neoplasm of gastrointestinal tract; Measures; Mentors; Metabolic; Methionine; Methodology; Methylation; Molecular; Molecular Epidemiology; Nutrient; Omega-3 Fatty Acids; Participant; Pattern; Plants; Plasma; Play; Process; Production; Race; Reporting; Research; Resources; Risk; Role; Rural; Sampling; Scientist; Training; Training Activity; Tumor Suppressor Genes; Tumor Suppressor Proteins; Vegan Diet; Writing; anticancer research; base; cancer health disparity; caucasian American; cdc Genes; cohort; colorectal cancer risk; cytokine; dietary; effective intervention; enterolactone; epigenetic marker; experience; genome wide methylation; health disparity; in silico; inflammatory milieu; metabolome; metabolomics; methylation pattern; methylome; microbial; polyphenol; prevent; symposium; whole genome; working group

Abstract African Americans suffer disparities in risk of gastrointestinal cancers, which are etiologically linked with inflammation. Dietary and other behavioral factors, rather than genetic, likely play a dominant role in explaining the disparity, as incidence of gastrointestinal cancers is much lower in rural Africans. Vegetarians in the Adventist Health Study-2 (AHS-2) cohort were found to have decreased risk for colorectal and gastrointestinal cancers relative to omnivores. Additionally, vegetarians have lower concentrations of inflammatory cytokines, and higher levels of anti-inflammatory bioactive compounds. Thus, habitual vegetarian and omnivorous dietary patterns may differentially regulate inflammation. However, there is a need for identification of other diet- related metabolites and molecular processes that influence inflammation and consequently cancer. The metabolome and DNA methylome are profoundly altered in cancer and also impacted by select foods or dietary conditions. However, it is unclear how they are influenced by dietary patterns characterized by consumption of plant- or animal-based foods. African Americans, who tend to have poorer nutrient profiles and dietary behaviors, have different metabolic and epigenetic signatures from Caucasians. Thus, these differences could be partly explained by diet. Secondary polyphenol and other plant-derived metabolites may prevent inflammation, while oxidative and energy-related metabolites that accumulate with consumption of animal-based foods may promote chronic inflammation. These different metabolite profiles may be characterized by opposing global or gene-specific alterations in methylation that influence genome stability and expression of cancer-relevant genes. Methyl-donating metabolites (folate, choline, and methionine) associated with a wide variety of foods influence cancer, but findings have not been consistent. It is plausible that the precise methylation activity of methyl donor and other metabolites is largely dependent on inflammatory status, which itself has been found to regulate methylation, and is defined by dietary pattern. Using blood samples from vegetarians and omnivores in the AHS-2 cohort, specific aims will examine the independent influences of dietary pattern and race on plasma metabolites and gene methylation, and determine if the effect of dietary patterns on these biomarker profiles is different in African Americans relative to Caucasians. In addition, correlations between a priori candidate, diet-associated metabolites and genes relevant to inflammation and cancer will be examined. The proposed project will provide new training in molecular epidemiology, genomics, and health disparities research. Activities for training include workshops, conferences, short courses, and seminars, along with grant writing classes and working groups. Research will be facilitated by the expertise of mentors experienced in experimental nutrition and metabolomics, statistical methodology and epidemiology, and cancer biology and health disparities, in conjunction with collaborating scientists with additional expertise in bioinformatics and epigenetics.

摘要 非裔美国人患胃肠道癌症的风险存在差异，这在病因学上与 炎症饮食和其他行为因素，而不是遗传，可能在解释 这一差异是因为非洲农村地区的胃肠道癌症发病率要低得多。素食主义者在 基督复临健康研究-2（AHS-2）队列发现， 相对于杂食动物的癌症。此外，素食者的炎症细胞因子浓度较低， 和更高水平的抗炎生物活性化合物。因此，习惯性素食和杂食饮食 模式可能差异调节炎症。然而，需要确定其他饮食- 相关的代谢物和分子过程，影响炎症和癌症。 代谢组和DNA甲基化组在癌症中发生了深刻的改变，并且也受到选择的影响。 食物或饮食条件。然而，目前还不清楚它们是如何受到饮食模式的影响， 食用植物性或动物性食物。非洲裔美国人，他们往往有较差的营养状况， 饮食行为，具有与高加索人不同的代谢和表观遗传特征。因此这些 差异可以部分由饮食解释。次级多酚和其它植物衍生的代谢物可 预防炎症，而氧化和能量相关的代谢产物，随着消费积累， 动物性食物可能会促进慢性炎症。这些不同的代谢物谱可能是 其特征在于影响基因组稳定性的甲基化的相反的整体或基因特异性改变， 癌症相关基因的表达。甲基供体代谢产物（叶酸、胆碱和蛋氨酸）相关 各种各样的食物都会影响癌症，但研究结果并不一致。这是似是而非的 甲基供体和其它代谢物的精确甲基化活性很大程度上取决于炎症状态， 它本身被发现可以调节甲基化，并由饮食模式定义。 使用AHS-2队列中素食者和杂食者的血液样本，具体目标将检查 饮食模式和种族对血浆代谢物和基因甲基化的独立影响， 确定饮食模式对这些生物标志物谱的影响在非洲裔美国人中是否不同， 白人。此外，先验候选物、饮食相关代谢物和基因之间的相关性 与炎症和癌症有关的疾病。拟议的项目将提供新的培训， 分子流行病学、基因组学和健康差异研究。培训活动包括讲习班， 会议、短期课程和研讨会，沿着赠款写作班和工作组。研究将 由经验丰富的导师在实验营养学和代谢组学，统计， 方法学和流行病学，癌症生物学和健康差异，与合作 在生物信息学和表观遗传学方面具有额外专业知识的科学家。