Published online Jun 14, 2020. doi: 10.3748/wjg.v26.i22.3076
Peer-review started: December 30, 2019
First decision: January 11, 2020
Revised: April 29, 2020
Accepted: May 13, 2020
Article in press: May 13, 2020
Published online: June 14, 2020
Disease-related single nucleotide polymorphisms (SNPs) based genetic risk score (GRS) has been proven to provide independent inherited risk other than family history in multiple cancer types.
To evaluate the potential of GRS in the prediction of pancreatic cancer risk.
In this case-control study (254 cases and 1200 controls), we aimed to evaluate the association between GRS and pancreatic ductal adenocarcinoma (PDAC) risk in the Chinese population. The GRS was calculated based on the genotype information of 18 PDAC-related SNPs for each study subject (personal genotyping information of the SNPs) and was weighted by external odd ratios (ORs).
GRS was significantly different in cases and controls (1.96 ± 3.84 in PDACs vs 1.09 ± 0.94 in controls, P < 0.0001). Logistic regression revealed GRS to be associated with PDAC risk [OR = 1.23, 95% confidence interval (CI): 1.13-1.34, P < 0.0001]. GRS remained significantly associated with PDAC (OR = 1.36, 95%CI: 1.06-1.74, P = 0.015) after adjusting for age and sex. Further analysis revealed an association of increased risk for PDAC with higher GRS. Compared with low GRS (< 1.0), subjects with high GRS (2.0) were 99% more likely to have PDAC (OR: 1.99, 95%CI: 1.30-3.04, P = 0.002). Participants with intermediate GRS (1.0-1.9) were 39% more likely to have PDAC (OR: 1.39, 95%CI: 1.03-1.84, P = 0.031). A positive trend was observed (P trend = 0.0006).
GRS based on PDAC-associated SNPs could provide independent information on PDAC risk and may be used to predict a high risk PDAC population.
Core tip: Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with no effective method for early diagnosis and high-risk population screening. In this pioneer study, we evaluated single nucleotide polymorphisms based genetic risk score (GRS) in the prediction of PDAC risk. Our results revealed that GRS was significantly associated with PDAC. Compared with low GRS (< 1.0), subjects with high GRS (2.0) were 99% more likely to be PDAC. Although further verification is needed, our study suggested that GRS was an independent risk factor for PDAC.