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(PUFA)(n-6和n-3)可能 在胰腺癌的发生发展中发挥不同的作用。然而，来自人类的发现 主要在高加索人中进行的研究一直是有限的，而且不一致。 传统研究有几个方法论上的局限性。拟议的项目将 应用一系列新的研究来解决对多不饱和脂肪酸在 胰腺癌病因学。多不饱和脂肪酸的暴露模式(数量和/或比率)各不相同 种族，非洲裔美国人(AA)在高端，亚洲人在低端。在K99公路上 阶段，吴博士将评估多不饱和脂肪酸饮食摄入与胰腺癌的关系 亚洲人、亚洲人、白人、拉美人和夏威夷原住民的风险研究 队列研究(上海妇女健康研究(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)和胰腺癌的数据 癌症病例对照联盟(PanC4)，吴博士还将调查两者之间的联系 基因决定的多不饱和脂肪酸水平和胰腺癌风险，主要是在使用 以脂肪组成的遗传得分为工具变量的孟德尔随机设计 酸血浓度相关变种。在R00阶段，吴博士将领导研究评估 诊断前红细胞中多不饱和脂肪酸水平是否与胰腺癌风险相关 在五个民族中采用嵌套式病例对照研究设计的SWHS、SMHS、SCCS 和MEC。这些优势互补的研究将使我们更好地理解 多不饱和脂肪酸在胰腺癌病因中的作用此外，吴博士将调查是否 多不饱和脂肪酸的遗传背景改变了多不饱和脂肪酸的饮食摄入量与糖尿病风险的关系 新陈代谢基因和GWAS识别的PC易感变异体 PanScan和PanC4。这将使我们更深入地了解 多不饱和脂肪酸膳食摄入与多不饱和脂肪酸吸收代谢的遗传背景 宿主易感性在胰腺癌发生中的作用。所获得的知识将 最终导致制定个性化的胰腺癌预防方案。 在K99/R00奖项期间，吴博士将获得更多营养和营养方面的技能和经验 分子流行病学，这将推动他成为一名独立调查员和 癌症流行病学领域的领军人物。这项研究项目的成果将被用于 在职业发展奖结束前制定并提交R01级项目。

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.