(Learn more about this study)
Initial CDAS Request Approval
Jan 27, 2020
Uncovering roles of polyunsaturated fatty acids (PUFA) in pancreatic cancer etiology: a gene-diet interaction study
Chronic inflammation is one of the very few established risk factors for pancreatic cancer. Research has shown that polyunsaturated fatty acids (PUFA) can influence inflammatory activities and insulin resistance; thus, they may be related to pancreatic cancer risk. Specifically, basic mechanism studies demonstrate that n-6 PUFA can potentially promote pancreatic cancer development through inducing inflammatory activities, while n-3 PUFA may impede pancreatic cancer development through competitively inhibiting the inflammatory effects of n-6 PUFA and improving insulin resistance. However, epidemiological studies assessing the association between PUFA and pancreatic cancer risk in humans have yielded inconsistent results. It is possible that genetics may play a role in the association of dietary PUFA intake and pancreatic cancer risk via influencing PUFA metabolism, as well as individual’s underlying susceptibility to pancreatic cancer. Failure to take genetic factors into consideration in prior epidemiological studies may have contributed to inconsistent findings. Therefore, a well-designed, adequately statistical powered study is needed to evaluate potential interaction between dietary PUFA intake and genetic factors on pancreatic cancer risk. PanScan and PanC4, with the large sample size and availability of both GWAS data and dietary information, provides an unparalleled opportunity to investigate these study hypotheses.
We hypothesize that functional variants in PUFA metabolizing genes and GWAS-identified pancreatic cancer susceptibility variants modify the association between dietary intake of PUFA and pancreatic cancer risk. In this study we will be using the pooled data from studies of PanScan and PanC4 which agreed to participate our project and we will need additional dietary data besides genetic and other covariate data.
1. To evaluate whether the dietary intake of PUFA interacts with relevant metabolizing gene variants in influencing risk of pancreatic cancer;
2. To evaluate whether the dietary intake of PUFA interacts with GWAS-identified pancreatic cancer susceptibility variants in influencing risk of pancreatic cancer.
Rachael Stolzenberg-Solomon, National Cancer Institute
Xiao-Ou Shu, Vanderbilt University Medical Center