Approved research

Genetic and epidemiologic risk factors for Pancreatic Cancer

Lay summary

To identify variants that influence risk of pancreatic cancer, we have performed Genome Wide Association Studies (GWAS) of pancreatic cancer within the NCI cohort consortium (PanScan I-III). In collaboration with investigators from the Pancreatic Cancer Case Control (PanC4) and PANcreatic Disease ReseArch (PANDoRA) consortia, we have identified 18 loci in the genome that influence risk of pancreatic ductal adenocarcinoma. We are now performing additional GWAS phases with newly diagnosed cases and would like to include pancreatic cancer cases and control subjects from the UK Biobank in this work to increase statistical power. We also plan to perform GWAS for GxE interactions and for survival. We have performed studies on epidemiologic and lifestyle risk factors for pancreatic cancer and plan to add UK Biobank data to our datasets to confirm previous associations and potentially identify new ones. The research proposed in this application, i.e. to identify inherited factors for pancreatic cancer is in the public?s interest as it will aid in the quest for better understanding of this deadly disease and may help improve prevention, diagnosis and hopefully treatment of this cancer. Germline genetic information (variants from GWAS genotyping and imputation) from pancreatic cancer cases as well as matched control subjects from the UK Biobank will be used to perform association analyses for pancreatic cancer risk. We plan to perform analyses for cases diagnosed with pancreatic adenocarcinoma and islet cell cancer. Adjustments will be made for age, gender, smoking, BMI, T2D and a diagnosis of pancreatitis. We also plan to perform associations between various epidemiologic and lifestyle factors and pancreatic cancer risk and interaction analysis for genetic and epidemiologic factors. The full UK Biobank cohort is requested for this study. The analysis will focus on individuals diagnosed with pancreatic cancer and control subjects drawn from the remaining set of participants. Individuals diagnosed with pancreatic adenocarcinoma (PDAC) and pancreatic islet cell cancer will be included as well as control subjects not diagnosed with cancer.

Scope extension:

To identify variants that influence risk of pancreatic cancer, we have performed Genome Wide Association Studies (GWAS) of pancreatic cancer within the NCI cohort consortium (PanScan I-III). In collaboration with investigators from the Pancreatic Cancer Case Control (PanC4) and PANcreatic Disease ReseArch (PANDoRA) consortia, we have identified 18 loci in the genome that influence risk of pancreatic ductal adenocarcinoma. We are now performing additional GWAS phases with newly diagnosed cases and would like to include pancreatic cancer cases and control subjects from the UK Biobank in this work to increase statistical power. We also plan to perform GWAS for GxE interactions and for survival. We have performed studies on epidemiologic and lifestyle risk factors for pancreatic cancer and plan to add UK Biobank data to our datasets to confirm previous associations and potentially identify new ones.

Update March 14th 2019: In this new scope we plan to assess risk of pancreatic cancer for various biomarkers, gene x biomarker interactions and assess correlations between genotypes and biomarker levels to investigate the genetics and underlying biology of inherited variants for pancreatic cancer.

Update August 28th, 2021: In this new scope we plan to assess polygenic risk scores for pancreatic cancer and their effects on risk by lifestyle and high risk mutations that predispose to pancreatic cancer.