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Polygenic and multifactorial scores for pancreatic ductal adenocarcinoma risk prediction
- Source :
- Journal of medical genetics, 58(6), 369-377. BMJ Publishing Group, JOURNAL OF MEDICAL GENETICS
- Publication Year :
- 2020
-
Abstract
- BackgroundMost cases of pancreatic ductal adenocarcinoma (PDAC) are asymptomatic in early stages, and the disease is typically diagnosed in advanced phases, resulting in very high mortality. Tools to identify individuals at high risk of developing PDAC would be useful to improve chances of early detection.ObjectiveWe generated a polygenic risk score (PRS) for PDAC risk prediction, combining the effect of known risk SNPs, and carried out an exploratory analysis of a multifactorial score.MethodsWe tested the associations of the individual known risk SNPs on up to 2851 PDAC cases and 4810 controls of European origin from the PANcreatic Disease ReseArch (PANDoRA) consortium. Thirty risk SNPs were included in a PRS, which was computed on the subset of subjects that had 100% call rate, consisting of 839 cases and 2040 controls in PANDoRA and 6420 cases and 4889 controls from the previously published Pancreatic Cancer Cohort Consortium I–III and Pancreatic Cancer Case-Control Consortium genome-wide association studies. Additional exploratory multifactorial scores were constructed by complementing the genetic score with smoking and diabetes.ResultsThe scores were associated with increased PDAC risk and reached high statistical significance (OR=2.70, 95% CI 1.99 to 3.68, p=2.54×10−10 highest vs lowest quintile of the weighted PRS, and OR=14.37, 95% CI 5.57 to 37.09, p=3.64×10−8, highest vs lowest quintile of the weighted multifactorial score).ConclusionWe found a highly significant association between a PRS and PDAC risk, which explains more than individual SNPs and is a step forward in the direction of the construction of a tool for risk stratification in the population.
- Subjects :
- 0301 basic medicine
Oncology
Male
medicine.medical_specialty
Multifactorial Inheritance
Pancreatic disease
genetic epidemiology
Population
Single-nucleotide polymorphism
Disease
pancreas and biliary tract
Polymorphism, Single Nucleotide
Risk Assessment
ABO Blood-Group System
03 medical and health sciences
0302 clinical medicine
Gene Frequency
Pancreatic cancer
Internal medicine
Genetics
medicine
oncology
Humans
education
Genetics (clinical)
Alleles
Early Detection of Cancer
Genetic association
education.field_of_study
business.industry
medicine.disease
Pancreatic Neoplasms
030104 developmental biology
Genetic epidemiology
030220 oncology & carcinogenesis
Cohort
Female
business
Carcinoma, Pancreatic Ductal
Subjects
Details
- Language :
- English
- ISSN :
- 00222593
- Database :
- OpenAIRE
- Journal :
- Journal of medical genetics, 58(6), 369-377. BMJ Publishing Group, JOURNAL OF MEDICAL GENETICS
- Accession number :
- edsair.doi.dedup.....a267bd63e2a9e7418632e88a73d56f47