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

• Published in: World journal of gastroenterology : WJG Vol. 26; no. 22; pp. 3076 - 3086
• Main Authors: Wang, Xiao-Yi, Chen, Hai-Tao, Jiang, De-Ke, Lin, Xiao-Ling, Yang, Feng, Jin, Chen, Fu, De-Liang, Xu, Jian-Feng
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Inc 14.06.2020
• Subjects: Case Control Study; Case-Control Studies; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Humans; Nucleotides; Pancreatic Neoplasms - epidemiology; Pancreatic Neoplasms - genetics; Polymorphism, Single Nucleotide; Risk Factors; Chinese population; Single nucleotide polymorphisms; Genome-wide association study; Genetic risk score; Pancreatic cancer
• ISSN: 1007-9327; 2219-2840; 2219-2840
• DOI: 10.3748/wjg.v26.i22.3076

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 1.09 ± 0.94 in controls, < 0.0001). Logistic regression revealed GRS to be associated with PDAC risk [OR = 1.23, 95% confidence interval (CI): 1.13-1.34, < 0.0001]. GRS remained significantly associated with PDAC (OR = 1.36, 95%CI: 1.06-1.74, = 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, = 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, = 0.031). A positive trend was observed ( 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.