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.
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