||1U01CA247283-01 Interpret this number
||Johns Hopkins University
||Multi-Ancestry Mapping of Pancreatic Cancer Susceptibility Loci
The goal of this application is to improve our understanding of the genetic basis of pancreatic cancer.
Pancreatic cancer is currently the 3rd leading cause of cancer death in the United States and it is projected
there will be 56,770 new pancreatic cancer diagnosed in the United States in 2019. Over the past decade the
incidence of pancreatic cancer has been steadily increasing. Despite the fact that pancreatic cancer incidence
rates are higher among African Americans compared to the US White population there have been no large-
scale genetic studies of pancreatic cancer in African Americans conducted to date. Furthermore, the relative
rarity of pancreatic ductal adenocarcinoma cancer (PDAC) and the rapidly fatal disease course has resulted in
limited samples sizes for all prior genome-wide association studies regardless of ancestral population. As
such many common PDAC loci have yet to be identified due to limited statistical power. Large-scale, diverse
collaborative studies of PDAC, are needed to dramatically increase our understanding of the inherited basis of
this deadly disease. Our proposal is designed to specifically address this need. First, we will conduct the first
genetic study of pancreatic cancer risk specifically focused on African Americans through whole genome
sequencing. As part of this study we are bringing together African American pancreatic cancer patients and
controls from our two, large established, successful pancreatic cancer consortiums, the Pancreatic Cancer
Cohort Consortium and the Pancreatic Cancer Case Control Consortium (PanC4). Secondly, we also expand
our power to detect pancreatic cancer association across all ethnic groups by doubling the size of prior GWAS
studies and conducting the first multi-ethnic genetic study of pancreatic cancer risk. We will conduct both
ancestry stratified and ancestry-informed analysis including both single variant and gene-based tests of
association of pancreatic cancer patients and controls. In addition, we will conduct gene x environment
interaction analysis with known risk factors of smoking, BMI, diabetes, and alcohol intake. The specific aims of
the project are to: Aim 1: To identify pancreatic cancer susceptibility loci in the African American population,
Aim 2: To identify novel pancreatic cancer loci through multi-ethnic GWAS analyses; Aim 3: To fine-map
regions associated with pancreatic cancer risk. In summary, this application seeks to identify novel pancreatic
cancer loci, conduct the first genetic analysis of pancreatic cancer in individuals of African Ancestry, and
leverage cross population genetic diversity to fine-map known pancreatic cancer susceptibility loci.
Smoking modifies pancreatic cancer risk loci on 2q21.3.
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Cancer research, 2021-02-11; , .