Genetic and Circulating Biomarker Data Improve Risk Prediction for Pancreatic Cancer in the General Population
- 1 May 2020
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Cancer Epidemiology, Biomarkers & Prevention
- Vol. 29 (5), 999-1008
- https://doi.org/10.1158/1055-9965.epi-19-1389
Abstract
Background: Pancreatic cancer is the third leading cause of cancer death in the United States, and 80% of patients present with advanced, incurable disease. Risk markers for pancreatic cancer have been characterized, but combined models are not used clinically to identify individuals at high risk for the disease. Methods: Within a nested case–control study of 500 pancreatic cancer cases diagnosed after blood collection and 1,091 matched controls enrolled in four U.S. prospective cohorts, we characterized absolute risk models that included clinical factors (e.g., body mass index, history of diabetes), germline genetic polymorphisms, and circulating biomarkers. Results: Model discrimination showed an area under ROC curve of 0.62 via cross-validation. Our final integrated model identified 3.7% of men and 2.6% of women who had at least 3 times greater than average risk in the ensuing 10 years. Individuals within the top risk percentile had a 4% risk of developing pancreatic cancer by age 80 years and 2% 10-year risk at age 70 years. Conclusions: Risk models that include established clinical, genetic, and circulating factors improved disease discrimination over models using clinical factors alone. Impact: Absolute risk models for pancreatic cancer may help identify individuals in the general population appropriate for disease interception.This publication has 53 references indexed in Scilit:
- An Absolute Risk Model to Identify Individuals at Elevated Risk for Pancreatic Cancer in the General PopulationPLOS ONE, 2013
- Inflammatory Plasma Markers and Pancreatic Cancer Risk: A Prospective Study of Five U.S. CohortsCancer Epidemiology, Biomarkers & Prevention, 2013
- International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancerGut, 2012
- Plasma 25-Hydroxyvitamin D and Risk of Pancreatic CancerCancer Epidemiology, Biomarkers & Prevention, 2012
- Family history of cancer and risk of pancreatic cancer: A pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan)International Journal of Cancer, 2010
- A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33Nature Genetics, 2010
- Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancerNature Genetics, 2009
- Cigarette Smoking and Pancreatic Cancer: A Pooled Analysis From the Pancreatic Cancer Cohort ConsortiumAmerican Journal of Epidemiology, 2009
- On criteria for evaluating models of absolute riskBiostatistics, 2005
- Final Report on the Aspirin Component of the Ongoing Physicians' Health StudyThe New England Journal of Medicine, 1989