Pancreatic cancer is a rapidly fatal tumor that causes a substantial public health burden worldwide. In the U.S., it is among the few malignancies with increasing incidence.
Because the pancreas is a metabolically important organ, many dietary and metabolic hypotheses have been posited for this cancer. Epidemiologic studies are challenging, both because of concerns about reverse causality related to latent disease and because most cohort studies lack substantial case numbers. In order to evaluate risk factors for this cancer, DCEG investigators have taken advantage of prospective data from DCEG cohorts and pooled consortia to study both modifiable risk factors and inherited causes of pancreatic cancer.
Rachael Stolzenberg-Solomon, senior investigator in the Metabolic Epidemiology Branch, conducts research to understand the etiology of pancreatic cancer. She seeks to identify modifiable risk factors, evaluate genetic susceptibility using agnostic and pathway approaches using GWAS data, and interrogate potential mechanisms that underlie associations using biomarker studies.
Temporal trends over the past 40 years by demographics and histologic types using data from the Surveillance, Epidemiology and End Results registries suggest increases in the incidence rate of pancreatic ductal adenocarcinoma (PDAC) across all ethnic groups since the mid-1990s. This increase parallels the changing prevalence of obesity and diabetes which are risk factors for pancreatic cancer.
Positive associations have been observed within prospective cohort studies for childhood and early adulthood BMI, overweight and obesity in older adults, and longer duration and cumulative overweight and obesity across a lifetime.
The diabetes associated with PDAC may be more heterogeneous than previously appreciated. In addition to Type 2 diabetes related to insulin resistance and adiposity, diabetes related to pancreatogenic disease and common single nucleotide polymorphisms in genes related to maturity onset diabetes of the young contributes to the association between diabetes and pancreatic cancer.
Inherited Causes of Pancreatic Cancer
Most susceptibility loci identified through GWAS, including those for pancreatic cancer identified by PanScan investigators and collaborative efforts, include multiple highly correlated variants that map to noncoding regions of the genome. Therefore, much of the efforts to understand the underlying biology of risk loci focuses on assessing allele-specific effects on noncoding gene regulatory elements and gene expression.
The Laboratory of Laufey Amundadottir focuses on discovering and characterizing inherited causes of pancreatic cancer. The overall aims of her research projects are to map susceptibility alleles for pancreatic cancer, identify functional variants and target genes underlying GWAS signals, investigate genetic regulation of gene expression and chromatin function, and the mechanisms by which they influence risk through genetic, genomic as well as molecular and cell biology approaches.
Learn more about the PanScan Study.