Potential Functional Variants in SMC2 and TP53 in the AURORA Pathway Genes and Risk of Pancreatic Cancer.
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The AURORA pathway participates in mitosis and cell division, and alterations in mitosis and cell division can lead to carcinogenesis. Therefore, genetic variants in the AURORA pathway genes may be associated with susceptibility to pancreatic cancer. To test this hypothesis, we used three large, publically available pancreatic cancer genome-wide association studies (GWASs) datasets (PanScan I, II/III and PanC4) to assess the associations of 7,168 single nucleotide polymorphisms (SNPs) in a set of 62 genes of this pathway with pancreatic cancer risk (8,477 cases and 6,946 controls of European ancestry). We identify 15 significant pancreatic cancer risk-associated SNPs in three genes (SMC2, ARHGEF7 and TP53) after correction for multiple comparisons by a false discovery rate (FDR) < 0.20. Through further linkage disequilibrium analysis, SNP functional prediction and stepwise logistic regression analysis, we focused on three SNPs: rs3818626 in SMC2, rs79447092 in ARHGEF7 and rs9895829 in TP53. We found that these three SNPs were associated with pancreatic cancer risk [odds ratio (OR) = 1.12, 95% confidence interval (CI) = 1.07-1.17 and P = 2.20E-06 for the rs3818626 C allele; OR = 0.76, CI = 0.66-0.88 and P = 1.46E-04 for the rs79447092 A allele; and OR = 0.82, CI = 0.74-0.91 and P = 1.51E-04 for the rs9895829 G allele]. Their joint effect as the number of protective genotypes (NPGs) also showed a significant association with pancreatic cancer risk (trend test P ≤ 0.001). Finally, we performed an eQTL analysis and found that rs3818626 and rs9895829 were significantly associated with SMC2 and TP53 mRNA expression levels in 373 lymphoblastoid cell lines, respectively. In conclusion, these three representative SNPs may be potentially susceptibility loci for pancreatic cancer and warrant additional validation.
Published Version (Please cite this version)10.1093/carcin/bgz029
Publication InfoAbbruzzese, James; Walsh, Kyle; Wei, Qingyi; Feng, Yun; Liu, Hongliang; Duan, Bensong; ... Zhang, Xuefeng (2019). Potential Functional Variants in SMC2 and TP53 in the AURORA Pathway Genes and Risk of Pancreatic Cancer. Carcinogenesis. 10.1093/carcin/bgz029. Retrieved from https://hdl.handle.net/10161/18494.
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D. C. I. Professor of Medical Oncology
My research interests include the clinical study and treatment of pancreatic cancer.
Associate Professor of Neurosurgery
Dr. Walsh’s research program focuses on genetic and epigenetic factors contributing to cancer predisposition in children and adults, with a special interest in brain tumors. This research is informed by both epidemiology and anthropological genetics, with computational work stressing statistical methodologies for “gene hunting” (e.g. GWAS, fine-mapping, admixture mapping, whole-genome sequencing). The laboratory engages in functional genomics research, investigating the biologi
Professor in Population Health Sciences
Qingyi Wei, MD, PhD, Professor in the Department of Medicine, is Associate Director for Cancer Control and Population Sciences, Co-leader of CCPS and Co-leader of Epidemiology and Population Genomics (Focus Area 1). He is a professor of Medicine and an internationally recognized epidemiologist focused on the molecular and genetic epidemiology of head and neck cancers, lung cancer, and melanoma. His research focuses on biomarkers and genetic determinants for the DNA repair deficient phenotype and
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