Genetic variants in the platelet‐derived growth factor subunit B gene associated with pancreatic cancer risk

• Published in: International journal of cancer 2018-04, Vol.142 (7), p.1322-1331
• Main Authors: Duan, Bensong, Hu, Jiangfeng, Liu, Hongliang, Wang, Yanru, Li, Hongyu, Liu, Shun, Xie, Jichun, Owzar, Kouros, Abbruzzese, James, Hurwitz, Herbert, Gao, Hengjun, Wei, Qingyi
• Format: Article
• Language: English
• Subjects: Aged; Alleles; Cancer; Case-Control Studies; Crk-Associated Substrate Protein - genetics; Female; Gene expression; Genes; Genetic diversity; Genetic Predisposition to Disease - genetics; Genetic variance; Genetic Variation; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genotype; Genotype & phenotype; Genotypes; Growth factors; Haplotypes; Health risks; Humans; Lymphoblastoid cell lines; Male; Males; Medical research; Middle Aged; Pancreatic cancer; pancreatic cancer susceptibility; Pancreatic Neoplasms - genetics; pathway analysis; Platelet-derived growth factor; Polymorphism, Single Nucleotide; Proto-Oncogene Proteins c-sis - genetics; Quantitative Trait Loci; Risk factors; Signal transduction; single nucleotide polymorphism; Tissues; Tumor cell lines; Tumors
• ISSN: 0020-7136; 1097-0215; 1097-0215
• DOI: 10.1002/ijc.31171

The platelet‐derived growth factor (PDGF) signaling pathway plays important roles in development and progression of human cancers. In our study, we aimed to identify genetic variants of the PDGF pathway genes associated with pancreatic cancer (PC) risk in European populations using three published genome‐wide association study datasets, which consisted of 9,381 cases and 7,719 controls. The expression quantitative trait loci (eQTL) analysis was also performed using data from the 1000 Genomes, TCGA and GTEx projects. As a result, we identified two potential susceptibility loci (rs5757573 and rs6001516) of PDGFB associated with PC risk [odds ratio (OR) = 1.10, 95% confidence interval (CI) = 1.05–1.16, and p = 4.70 × 10−5 for the rs5757573 C allele and 1.21, 1.11–1.32, and 2.01 × 10−5 for the rs6001516 T allele]. Haplotype analysis revealed that the C‐T haplotype carriers had a significantly increased risk of PC than those carrying the T‐C haplotype (OR = 1.23, 95% CI = 1.12–1.34, p =5.00 × 10−6). The multivariate regression model incorporating the number of unfavorable genotypes (NUGs) with age and sex showed that carriers with 1–2 NUGs, particularly among 60–70 age group or males, had an increased risk of PC, compared to those without NUG. Furthermore, the eQTL analysis revealed that both loci were correlated with a decreased mRNA expression level of PDGFB in lymphoblastoid cell lines and pancreatic tumor tissues (p = 0.015 and 0.071, respectively). Our results suggest that genetic variants in PDGFB may play a role in susceptibility to PC. Further population and functional validations of our findings are warranted. What's new? There have been so many genetic variants that are likely to be associated with pancreatic cancer (PC) risk. In this analysis, the authors chose to focus on those variants in genes involved in the platelet‐derived growth factor (PDGF)‐signaling pathway, which has been implicated in many other cancers. Using datasets from genome‐wide association studies, they identified two loci in the PDGF subunit B (PDGFB) gene that were correlated with increased PC risk and possibly also with decreased expression of PDGFB mRNA in PC tumors. These results suggest that genetic variants in PDGFB may thus play a role in PC susceptibility.