Genetic polymorphisms associated with pancreatic cancer survival: a genome‐wide association study

Abstract

Previous findings on the association of genetic factors and pancreatic cancer survival are limited and inconsistent. In a two-stage study, we analyzed the existing genome-wide association study dataset of 868 pancreatic cancer patients from MD Anderson Cancer Center in relation to overall survival using Cox regression. Top hits were selected for replication in another 820 patients from the same institution using the Taqman genotyping method. Functional annotation, pathway analysis, and gene expression analysis were conducted using existing software and databases. We discovered genome-wide significant associations of patient survival with three imputed SNPs which, in complete LD (r2=1), were intronic SNPs of the PAIP2B (rs113988120) and DYSF genes (rs112493246 and rs138529893) located on chromosome 2. The variant alleles were associated with a 3.06-fold higher risk of death (95% confidence interval [CI]=2.10-4.47, P = 6.4 × 10−9) after adjusting for clinical factors. Eleven SNPs were tested in the replication study and the association of rs113988120 with survival was confirmed (HR: 1.57, 95%CI: 1.13-2.20, P = 0.008). In silico analysis found rs1139988120 might lead to altered motif. This locus is in LD (D′=0.77) with 3 eQTL SNPs near or belong to the NAGK and MCEE genes. According to The Cancer Genome Atlas data and our previous RNA-sequencing data, the mRNA expression level of PAIP2B but not NAGK, MCEE or DYSF was significantly lower in pancreatic tumors than in normal adjacent tissues. Additional validation efforts and functional studies are warranted to demonstrate whether PAIP2B is a novel tumor suppressor gene and a potential therapeutic target for pancreatic cancer.

Expression of KLF9 in pancreatic cancer and its effects on the invasion, migration, apoptosis, cell cycle distribution, and proliferation of pancreatic cancer cell lines

“…The low expression of KLF9 was associated with poor progression and total survival in patients with pancreatic cancer, which was consistent with previous studies in cancers of other organs (29,30). Pancreatic cancer is a heterogeneous and complex disease since the development of pancreatic cancer involves a variety of genetic changes (31). Our research focused on the overexpression of KLF9 which inhibited the malignant behavior of pancreatic cancer in vitro, consistent with previous published studies (17,32).…”

Common variants in IL17F gene contributed to the risk of hip osteoarthritis susceptibility in Han Chinese population

“…as significantly associated with the risk of HOA based on a sample with Chinese Han ancestry. The effect direction of SNP rs763780 observed in our study was the same as the results reported by Vrgoc et al 10 The study conducted by Vrgoc 20 response to gemcitabine in pancreatic cancer and survival in pancreatic cancer, 21,22 and initial alcohol sensitivity. 23 However, the gene IL17F has not been reported as a susceptible locus for OA/ HOA in GWAS, although 16 GWAS studies for OA/HOA have been published.…”

Family Socioeconomic Position and Lung Cancer Risk: A Meta-analysis and a Mendelian Randomization Study

“…The analysis was conducted to estimate the effect of family SEP in childhood (X) on the risk of lung cancer (Y) using genetic variants (g), and the causal estimate is equal to Yg/Xg [54]. For the association between genetic variants and family SEP in childhood (Xg), summary data were utilized from published Genome-Wide Association Studies (GWASs), [55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70] Table 2). [62] We selected uncorrelated variants to construct the instrumental variables in the two-sample MR analysis.…”