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. 2020 Jun 14;26(22):3076-3086.
doi: 10.3748/wjg.v26.i22.3076.

Single-nucleotide polymorphisms based genetic risk score in the prediction of pancreatic cancer risk

Xiao-Yi Wang  1 , Hai-Tao Chen  2 , Rong Na  3 , De-Ke Jiang  2 , Xiao-Ling Lin  4 , Feng Yang  1 , Chen Jin  1 , De-Liang Fu  5 , Jian-Feng Xu  6
Affiliations

Single-nucleotide polymorphisms based genetic risk score in the prediction of pancreatic cancer risk

Xiao-Yi Wang et al. World J Gastroenterol. .

Abstract

Background: 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.

Aim: To evaluate the potential of GRS in the prediction of pancreatic cancer risk.

Methods: 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).

Results: 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).

Conclusion: GRS based on PDAC-associated SNPs could provide independent information on PDAC risk and may be used to predict a high risk PDAC population.

Keywords: Chinese population; Genetic risk score; Genome-wide association study; Pancreatic cancer; Single nucleotide polymorphisms.

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Conflict of interest statement

Conflict-of-interest statement: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

Figures

Figure 1
Figure 1
Increased risk of pancreatic ductal adenocarcinoma with increased genetic risk score in a univariate model. A: 1, 2 being genetic risk score cut-off value; B: Percentile as cut-off value. GRS: Genetic risk score.
Figure 2
Figure 2
Percentage of pancreatic ductal adenocarcinoma cases in different genetic risk score groups. PDAC: Pancreatic ductal adenocarcinoma; GRS: Genetic risk score.
Figure 3
Figure 3
Increased risk of pancreatic ductal adenocarcinoma with increased genetic risk score in multivariate model adjusted for age and sex. GRS: Genetic risk score.
See this image and copyright information in PMC

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