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: 10385777
• 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 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10385777
• 关键词: African; African American population; 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; Health Disparities Research; 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.

抽象的 非裔美国人患胃肠道癌症的风险存在差异，其病因与 炎。饮食和其他行为因素，而不是遗传，可能在解释中起主导作用。 差异，因为非洲农村地区胃肠道癌症的发病率要低得多。素食者在 Adventist Health Study-2 (AHS-2) 队列被发现结直肠和胃肠道疾病的风险降低 癌症与杂食动物有关。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，习惯性的素食和杂食饮食 模式可能会差异性地调节炎症。然而，需要确定其他饮食 影响炎症并进而影响癌症的相关代谢物和分子过程。 代谢组和 DNA 甲基化组在癌症中发生了深刻的改变，并且还受到选择的影响 食物或饮食条件。然而，目前尚不清楚它们如何受到饮食模式的影响，其特征是 食用植物或动物性食物。非裔美国人的营养成分往往较差 饮食行为与白种人具有不同的代谢和表观遗传特征。因此，这些 饮食差异可以部分解释。次级多酚和其他植物来源的代谢物可能 预防炎症，同时随着消耗而积累的氧化和能量相关代谢物 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 其特点是反对影响基因组稳定性的全局或基因特异性甲基化改变， 癌症相关基因的表达。相关的甲基供给代谢物（叶酸、胆碱和蛋氨酸） 多种食物都会影响癌症，但研究结果并不一致。似乎有道理的是 甲基供体和其他代谢物的精确甲基化活性很大程度上取决于炎症状态， 人们发现它本身可以调节甲基化，并且由饮食模式决定。 使用 AHS-2 队列中素食者和杂食动物的血液样本，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，以及 确定饮食模式对这些生物标志物谱的影响在非裔美国人相对中是否不同 对白人来说。此外，先验候选物、饮食相关代谢物和基因之间的相关性 将检查与炎症和癌症相关的问题。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。培训活动包括研讨会、 会议、短期课程和研讨会，以及拨款写作课程和工作组。研究将 得到在实验营养和代谢组学、统计方面经验丰富的导师的专业知识的帮助 方法论和流行病学、癌症生物学和健康差异，以及合作 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。

项目成果

Plasma metabolomics profiles in Black and White participants of the Adventist Health Study-2 cohort.

• DOI: 10.1186/s12916-023-03101-4
• 发表时间: 2023-10-31
• 期刊: BMC MEDICINE
• 影响因子: 9.3
• 作者: Butler, Fayth M.;Utt, Jason;Mathew, Roy O.;Casiano, Carlos A.;Montgomery, Suzanne;Wiafe, Seth A.;Lampe, Johanna W.;Fraser, Gary E.
• 通讯作者: Fraser, Gary E.

The Biology of Veganism: Plasma Metabolomics Analysis Reveals Distinct Profiles of Vegans and Non-Vegetarians in the Adventist Health Study-2 Cohort.

• DOI: 10.3390/nu14030709
• 发表时间: 2022-02-08
• 期刊: Nutrients
• 影响因子: 5.9
• 作者: Miles FL;Orlich MJ;Mashchak A;Chandler PD;Lampe JW;Duerksen-Hughes P;Fraser GE
• 通讯作者: Fraser GE

DNA Methylation Profiles of Vegans and Non-Vegetarians in the Adventist Health Study-2 Cohort.

• DOI: 10.3390/nu12123697
• 发表时间: 2020-11-30
• 期刊: Nutrients
• 影响因子: 5.9
• 作者: Miles FL;Mashchak A;Filippov V;Orlich MJ;Duerksen-Hughes P;Chen X;Wang C;Siegmund K;Fraser GE
• 通讯作者: Fraser GE