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

Publication ,  Journal Article
Duan, B; Hu, J; Liu, H; Wang, Y; Li, H; Liu, S; Xie, J; Owzar, K; Abbruzzese, J; Hurwitz, H; Gao, H; Wei, Q
Published in: Int J Cancer
April 1, 2018

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.

Duke Scholars

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Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

April 1, 2018

Volume

142

Issue

7

Start / End Page

1322 / 1331

Location

United States

Related Subject Headings

  • Quantitative Trait Loci
  • Proto-Oncogene Proteins c-sis
  • Polymorphism, Single Nucleotide
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Humans
  • Genotype
  • Genome-Wide Association Study
 

Citation

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Duan, B., Hu, J., Liu, H., Wang, Y., Li, H., Liu, S., … Wei, Q. (2018). Genetic variants in the platelet-derived growth factor subunit B gene associated with pancreatic cancer risk. Int J Cancer, 142(7), 1322–1331. https://doi.org/10.1002/ijc.31171
Duan, Bensong, Jiangfeng Hu, Hongliang Liu, Yanru Wang, Hongyu Li, Shun Liu, Jichun Xie, et al. “Genetic variants in the platelet-derived growth factor subunit B gene associated with pancreatic cancer risk.Int J Cancer 142, no. 7 (April 1, 2018): 1322–31. https://doi.org/10.1002/ijc.31171.
Duan B, Hu J, Liu H, Wang Y, Li H, Liu S, et al. Genetic variants in the platelet-derived growth factor subunit B gene associated with pancreatic cancer risk. Int J Cancer. 2018 Apr 1;142(7):1322–31.
Duan, Bensong, et al. “Genetic variants in the platelet-derived growth factor subunit B gene associated with pancreatic cancer risk.Int J Cancer, vol. 142, no. 7, Apr. 2018, pp. 1322–31. Pubmed, doi:10.1002/ijc.31171.
Duan B, Hu J, Liu H, Wang Y, Li H, Liu S, Xie J, Owzar K, Abbruzzese J, Hurwitz H, Gao H, Wei Q. Genetic variants in the platelet-derived growth factor subunit B gene associated with pancreatic cancer risk. Int J Cancer. 2018 Apr 1;142(7):1322–1331.
Journal cover image

Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

April 1, 2018

Volume

142

Issue

7

Start / End Page

1322 / 1331

Location

United States

Related Subject Headings

  • Quantitative Trait Loci
  • Proto-Oncogene Proteins c-sis
  • Polymorphism, Single Nucleotide
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Humans
  • Genotype
  • Genome-Wide Association Study