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Grant Details

Grant Number: 5R00CA218892-04 Interpret this number
Primary Investigator: Wu, Lang
Organization: University Of Hawaii At Manoa
Project Title: Uncovering Roles of Polyunsaturated Fatty Acids in Pancreatic Cancer Etiology
Fiscal Year: 2021


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.


Mendelian Randomization Analysis of n-6 Polyunsaturated Fatty Acid Levels and Pancreatic Cancer Risk.
Authors: Ghoneim D.H. , Zhu J. , Zheng W. , Long J. , Murff H.J. , Ye F. , Setiawan V.W. , Wilkens L.R. , Khankari N.K. , Haycock P. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2020 12; 29(12), p. 2735-2739.
EPub date: 2020-09-23.
PMID: 32967863
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A Transcriptome-Wide Association Study Identifies Candidate Susceptibility Genes for Pancreatic Cancer Risk.
Authors: Liu D. , Zhou D. , Sun Y. , Zhu J. , Ghoneim D. , Wu C. , Yao Q. , Gamazon E.R. , Cox N.J. , Wu L. .
Source: Cancer research, 2020-10-15; 80(20), p. 4346-4354.
EPub date: 2020-09-09.
PMID: 32907841
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Associations between Genetically Predicted Blood Protein Biomarkers and Pancreatic Cancer Risk.
Authors: Zhu J. , Shu X. , Guo X. , Liu D. , Bao J. , Milne R.L. , Giles G.G. , Wu C. , Du M. , White E. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2020 07; 29(7), p. 1501-1508.
EPub date: 2020-05-21.
PMID: 32439797
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Analysis of Over 140,000 European Descendants Identifies Genetically Predicted Blood Protein Biomarkers Associated with Prostate Cancer Risk.
Authors: Wu L. , Shu X. , Bao J. , Guo X. , Kote-Jarai Z. , Haiman C.A. , Eeles R.A. , Zheng W. , PRACTICAL, CRUK, BPC3, CAPS, PEGASUS Consortia .
Source: Cancer research, 2019-09-15; 79(18), p. 4592-4598.
EPub date: 2019-07-23.
PMID: 31337649
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Identification of Novel Susceptibility Loci and Genes for Prostate Cancer Risk: A Transcriptome-Wide Association Study in Over 140,000 European Descendants.
Authors: Wu L. , Wang J. , Cai Q. , Cavazos T.B. , Emami N.C. , Long J. , Shu X.O. , Lu Y. , Guo X. , Bauer J.A. , et al. .
Source: Cancer research, 2019-07-01; 79(13), p. 3192-3204.
EPub date: 2019-05-17.
PMID: 31101764
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A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer.
Authors: Wu L. , Shi W. , Long J. , Guo X. , Michailidou K. , Beesley J. , Bolla M.K. , Shu X.O. , Lu Y. , Cai Q. , et al. .
Source: Nature genetics, 2018 07; 50(7), p. 968-978.
EPub date: 2018-06-18.
PMID: 29915430
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