Analysis of Pancreatic Cancer Genetic Risk Factors in a Multi-Ethnic Population Sample

Background: Pancreatic cancer (PC) has one of the highest mortality to incidence ratio of all cancers. Early identification of at-risk individuals should permit early diagnosis. Genome-wide association studies showed the association of several genetic variants with PC risk in multi-ethnic populations. Our objective was to examine the association of these genetic variants with PC in a population sample from Kuwait. Methods: DNA samples from 103 pancreatic ductal adenocarcinoma (PDAC) specimens and 132 healthy controls were used for genotyping ABO rs505922, BCAR1 rs7190458, LINC-PINT rs6971499, HNF1B rs4795218, VDR rs2228570 rs731236, and PRSS1 rs111033565 rs111033568 rs387906698 and rs267606982 using TaqMan genotyping assays, and VDR expression was performed by immunocytochemistry. Results: ABO rs505922C and VDR rs2228570A were associated with PDAC risk (odds ratio (OR): 1.55, 95% confidence interval (CI): 1.07 - 2.24, P = 0.027; OR: 1.64, 95% CI: 1.09 - 2.48, P = 0.024; respectively). An unweighted polygenic risk score (ABO rs505922, BCAR1 rs7190458, LINC-PINT rs6971499, and HNF1B rs4795218) was significantly associated with PDAC risk (beta: -0.11, 95% CI: -0.15 to -0.05, P < 0.001). VDR expression was downregulated or absent in most PDAC specimens regardless of VDR haplotype. Conclusion: ABO rs505922C and VDR rs2228570A are PDAC genetic risk factors in our population. Ethnicity influences the association of reported genetic PDAC risk factors and should be adjusted for when performing PDAC genetic risk estimations. Investigation of these genetic risk factors in other ethnic populations is a necessity to evaluate their PDAC risk prediction potential.