Associations between genetic variants of KIF5B, FMN1, and MGAT3 in the cadherin pathway and pancreatic cancer risk

xloma.fota13 shared this article with you from Inoreader Associations between genetic variants of KIF5B, FMN1, and MGAT3 in the cadherin pathway and pancreatic cancer risk Via Cancer Medicine We assessed associations between genetic variants in 109 cadherin‐related genes and pancreatic cancer risk by using genotyping data from two available genome‐wide association study datasets for 8477 cases and 6946 controls of European ancestry. We identified three novel PanC risk‐associated SNPs, KIF5B rs211304 C > G, FMN1 rs117648907 C > T and MGAT3 rs34943118 T > C. We also demonstrated potential functions of these risk loci, especially for the SNP rs211304 and rs34943118, to be associated with mRNA expression levels of KIF5B and MGAT3, respectively. Abstract Because the cadherin‐mediated signaling pathway promotes cancer progression, we assessed associations between genetic variants in 109 cadherin‐related genes and risk of pancreatic cancer (PanC) by using genotyping data from publically available genome‐wide association studies (GWAS) datasets comprising 15,423 individuals of European ancestry. After initial single‐locus analyses and subsequent meta‐analysis with multiple testing correction for 29,963 single‐nucleotide polymorphisms (SNPs), 11 SNPs remained statistically significant (p < 0.05). In the stepwise logistic regression analysis, three independent PanC risk‐associated SNPs (KIF5B rs211304 C > G, FMN1 rs117648907 C > T, and MGAT3 rs34943118 T > C) remained statistically significant (p < 0.05), with odds ratios of 0.89 (95% confidence interval = 0.82–0.95 and p = 6.93 ×&nbs p;10−4), 1.33 (1.13–1.56 and 2.11 × 10−4), and 1.11 (1.05–1.17 and 8.10 × 10−5), respectively. Combined analysis of unfavorable genotypes of these three independent SNPs showed an upward trend in the genotype‐risk association (p trend < 0.001). Expression quantitative trait loci analyses indicated that the rs211304 G and rs34943118 C alleles were associated with increased mRNA expression levels of KIF5B and MGAT3, respectively (all p < 0.05). Additional bioinformatics prediction suggested that these three SNPs may affect enhancer histone marks that likely have an epigenetic effect on the genes. Our findings provide biological clues for these PanC risk‐associated SNPs in cadherin‐related genes in European ancestry populations, possibly by regulating the expression of the affected genes. However, our findings need to be validated in additional population, molecular and mechanistic investigations. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.