Uncovering roles of polyunsaturated fatty acids in pancreatic cancer etiology

基础研究表明，不同的多不饱和脂肪酸（n-6和n-3）可能 在胰腺癌的发展中起着不同的作用。然而，人类的研究结果 主要在高加索人中进行的研究有限且不一致。 传统的研究受到一些方法上的限制。拟议项目将 应用一系列新的研究来解决理解PUFA在以下方面作用的差距： 胰腺癌的病因多不饱和脂肪酸的暴露模式（数量和/或比例）在不同地区不同。 种族，非洲裔美国人（AAs）在高端，亚洲人在低端。在K99 吴博士将评估PUFA饮食摄入与胰腺癌之间的关系 亚洲人，AAs，白人，拉丁美洲人和夏威夷原住民的风险，使用四个前瞻性数据 队列研究（上海女性健康研究（SWHS），上海男性健康研究 （SMHS），南方社区队列研究（SCCS）和多种族队列研究 （MEC））。使用来自胰腺癌队列联盟（PanScan）和胰腺癌 癌症病例控制联盟（PanC 4），吴博士还将研究之间的关联 基因决定的PUFA水平和胰腺癌风险主要在高加索人中使用， 以脂肪酸组成的遗传评分为工具变量的孟德尔随机设计 酸血水平相关的变异。在R 00阶段，吴博士将领导研究， 诊断前红细胞中的PUFA水平是否与胰腺癌风险相关 采用SWHS、SMHS、SCCS的巢式病例对照研究设计， 和MEC。这些优势互补的研究将有助于更好地了解 PUFA在胰腺癌病因学中的作用。此外，吴博士将调查是否 PUFA的遗传背景改变了膳食摄入PUFA与PC风险的关联 代谢基因和GWAS鉴定的PC易感性变体， PanScan和PanC 4。这将有助于深入了解 PUFA膳食摄入量和吸收和代谢PUFA的遗传背景以及 宿主易感性对胰腺癌发生影响所获得的知识将 最终导致个体化胰腺癌预防计划的发展。 在此K99/R 00奖励期间，吴博士将获得营养和营养方面的额外技能和经验， 分子流行病学，这将推动他成为一名独立的研究人员， 癌症流行病学领域的领导者。该研究项目的成果将用于 在完成职业发展奖之前，开发并提交R 01级别的项目。

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.