Uncovering roles of polyunsaturated fatty acids in pancreatic cancer etiology

揭示多不饱和脂肪酸在胰腺癌病因学中的作用

• 批准号: 9982226
• 负责人: Lang Wu
• 金额: $ 24.9万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9982226
• 关键词: Address; African American; Asians; Award; Basic Science; Biological; Blood; Cancer Biology; Cancer Etiology; Caucasians; Cohort Studies; Communities; Data; Development; Diagnosis; Diet; Dietary Fatty Acid; Dietary intake; Erythrocytes; Ethnic Origin; Ethnic group; Etiology; Fatty Acids; Foundations; Genes; Genetic; Genetic Variation; Genetic study; Habits; Human; Individual; Inflammatory; Intake; K-Series Research Career Programs; Knowledge; Latino; Lead; Logistics; Malignant neoplasm of pancreas; Measurement; Mentors; Metabolism; Methodology; Molecular; Molecular Epidemiology; Molecular Genetics; N-3 polyunsaturated fatty acid; Native Hawaiian; Nested Case-Control Study; Nutritional; Observational Study; Pattern; Phase; Play; Polyunsaturated Fatty Acids; Population; Predisposition; Prevention program; Prevention strategy; Prospective cohort study; Randomized; Regression Analysis; Research; Research Design; Research Personnel; Research Project Grants; Residual state; Resources; Role; Sample Size; Selection Bias; Series; Susceptibility Gene; United States; Variant; Woman; Women' s Health; absorption; cancer epidemiology; cancer prevention; cancer risk; career; case control; cohort; design; epidemiology study; experience; genetic epidemiology; genetic variant; genome wide association study; individualized prevention; interdisciplinary approach; interest; male health; mortality; nutritional epidemiology; pancreas development; personalized strategies; prospective; prospective test; skills

Basic research suggests that different polyunsaturated fatty acids (PUFA) (n-6 and n-3) may play differentiated roles in pancreatic cancer development. However, findings from human studies, which are conducted primarily among Caucasians, have been limited and inconsistent. Conventional studies suffer from several methodological limitations. The proposed project will apply a series of new studies to address the gap of understanding the role of PUFA in pancreatic cancer etiology. The exposure patterns of PUFA (amounts and/or ratio) differ across ethnicities, with African Americans (AAs) in the high end and Asians in the low end. In the K99 phase, Dr. Wu will evaluate the association between PUFA dietary intake and pancreatic cancer risk in Asians, AAs, Whites, Latinos, and Native Hawaiians using data from four prospective cohort studies (the Shanghai Women's Health Study (SWHS), the Shanghai Men's Health Study (SMHS), the Southern Community Cohort Study (SCCS), and the Multiethnic Cohort Study (MEC)). Using data from the Pancreatic Cancer Cohort Consortium (PanScan) and Pancreatic Cancer Case-Control Consortium (PanC4), Dr. Wu will also investigate the association between genetically-determined PUFA levels and pancreatic cancer risk primarily in Caucasians using a Mendelian randomization design with instrumental variable of genetic scores composed of fatty acids blood level associated variants. In the R00 phase, Dr. Wu will lead research to assess whether PUFA levels in pre-diagnosis red blood cells are associated with pancreatic cancer risk in the five ethnic groups using a nested case-control study design of the SWHS, SMHS, SCCS and MEC. These studies with complementary strengths will lead a better understanding of the role of PUFA in pancreatic cancer etiology. Furthermore, Dr. Wu will investigate whether the association of dietary intake of PUFA with PC risk is modified by genetic background of PUFA metabolizing genes and GWAS-identified PC susceptibility variants using resources from PanScan and PanC4. This will provide an in depth understanding of the interaction between PUFA dietary intake and genetic background in absorbing and metabolizing PUFA as well as host susceptibility on development of pancreatic cancer. The knowledge gained would eventually lead to a development of individualized pancreatic cancer prevention program. During this K99/R00 award Dr. Wu will gain additional skills and experience in nutritional and molecular epidemiology, which will propel him into a career as an independent investigator and leader in the field of cancer epidemiology. The findings from this research project will be used to develop and submit R01 level projects before the completion of the Career Development Award.

基础研究表明，不同的多不饱和脂肪酸（PUFA）（N-6和N-3）可能 在胰腺癌发展中发挥不同的作用。但是，人类的发现 主要在高加索人中进行的研究是有限且不一致的。 常规研究受到了几种方法上的局限性。拟议的项目将 应用一系列新研究来解决理解PUFA在 胰腺癌病因。 PUFA的曝光模式（金额和/或比率）在各个方面有所不同 种族，在高端的非裔美国人（AAS）和低端的亚洲人。在K99中 阶段，Wu博士将评估PUFA饮食摄入与胰腺癌之间的关联 使用来自四个潜在的数据，亚洲人，AAS，白人，拉丁裔和夏威夷人的风险 队列研究（上海妇女健康研究（SWHS），上海男子健康研究 （SMHS），南方社区队列研究（SCC）和多民族队列研究 （MEC））。使用来自胰腺癌队列联盟（Panscan）和胰腺的数据 癌症病例对照联盟（PANC4），Wu博士还将调查 遗传确定的PUFA水平和胰腺癌主要在高加索人中使用A Mendelian随机设计具有遗传评分的仪器变量，由脂肪组成 酸血液水平相关的变体。在R00阶段，Wu博士将领导研究以评估 诊断前红细胞中的PUFA水平是否与胰腺癌风险有关 在五个族裔中，使用SWHS，SMH，SCCS的嵌套案例对照研究设计 和MEC。这些具有互补优势的研究将使人们更好地理解 PUFA在胰腺癌病因中的作用。此外，吴博士将调查是否 PUFA的遗传背景改变了PUFA饮食摄入量与PC风险的关联 使用来自 Panscan和Panc4。这将深入了解 PUFA饮食摄入量和吸收和代谢PUFA的遗传背景以及 宿主对胰腺癌发展的敏感性。获得的知识将 最终导致了个性化胰腺癌预防计划的发展。 在此K99/R00奖期间，Wu博士将获得营养和营养方面的其他技能和经验 分子流行病学，这将使他成为独立研究者的职业， 癌症流行病学领域的领导者。该研究项目的发现将用于 在完成职业发展奖之前，开发和提交R01级项目。