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Genetic variants of the peroxisome proliferator-activated receptor (PPAR) signaling pathway genes and risk of pancreatic cancer.

Publication ,  Journal Article
Liu, X; Qian, D; Liu, H; Abbruzzese, JL; Luo, S; Walsh, KM; Wei, Q
Published in: Mol Carcinog
August 2020

Because the peroxisome proliferator-activated receptor (PPAR) signaling pathway is involved in development and progression of pancreatic cancer, we investigated associations between genetic variants of the PPAR pathway genes and pancreatic cancer risk by using three published genome-wide association study datasets including 8477 cases and 6946 controls of European ancestry. Expression quantitative trait loci (eQTL) analysis was also performed for correlations between genotypes of the identified genetic variants and messenger RNA (mRNA) expression levels of their genes by using available databases of the 1000 Genomes, TCGA, and GTEx projects. In the single-locus logistic regression analysis, we identified 1141 out of 17 532 significant single-nucleotide polymorphisms (SNPs) in 112 PPAR pathway genes. Further multivariate logistic regression analysis identified three independent, potentially functional loci (rs12947620 in MED1, rs11079651 in PRKCA, and rs34367566 in PRKCB) for pancreatic cancer risk (odds ratio [OR] = 1.11, 95% confidence interval [CI], [1.06-1.17], P = 5.46 × 10-5 ; OR = 1.10, 95% CI, [1.04-1.15], P = 1.99 × 10-4 ; and OR = 1.09, 95% CI, [1.04-1.14], P = 3.16 × 10-4 , respectively) among 65 SNPs that passed multiple comparison correction by false discovery rate (< 0.2). When risk genotypes of these three SNPs were combined, carriers with 2 to 3 unfavorable genotypes (NUGs) had a higher risk of pancreatic cancer than those with 0 to 1 NUGs. The eQTL analysis showed that rs34367566 A>AG was associated with decreased expression levels of PRKCB mRNA in 373 lymphoblastoid cell lines. Our findings indicate that genetic variants of the PPAR pathway genes, particularly MED1, PRKCA, and PRKCB, may contribute to susceptibility to pancreatic cancer.

Duke Scholars

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Published In

Mol Carcinog

DOI

EISSN

1098-2744

Publication Date

August 2020

Volume

59

Issue

8

Start / End Page

930 / 939

Location

United States

Related Subject Headings

  • Survival Rate
  • Quantitative Trait Loci
  • Protein Kinase C-alpha
  • Protein Kinase C beta
  • Prognosis
  • Polymorphism, Single Nucleotide
  • Peroxisome Proliferator-Activated Receptors
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • Middle Aged
 

Citation

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Liu, X., Qian, D., Liu, H., Abbruzzese, J. L., Luo, S., Walsh, K. M., & Wei, Q. (2020). Genetic variants of the peroxisome proliferator-activated receptor (PPAR) signaling pathway genes and risk of pancreatic cancer. Mol Carcinog, 59(8), 930–939. https://doi.org/10.1002/mc.23208
Liu, Xiaowen, Danwen Qian, Hongliang Liu, James L. Abbruzzese, Sheng Luo, Kyle M. Walsh, and Qingyi Wei. “Genetic variants of the peroxisome proliferator-activated receptor (PPAR) signaling pathway genes and risk of pancreatic cancer.Mol Carcinog 59, no. 8 (August 2020): 930–39. https://doi.org/10.1002/mc.23208.
Liu X, Qian D, Liu H, Abbruzzese JL, Luo S, Walsh KM, et al. Genetic variants of the peroxisome proliferator-activated receptor (PPAR) signaling pathway genes and risk of pancreatic cancer. Mol Carcinog. 2020 Aug;59(8):930–9.
Liu, Xiaowen, et al. “Genetic variants of the peroxisome proliferator-activated receptor (PPAR) signaling pathway genes and risk of pancreatic cancer.Mol Carcinog, vol. 59, no. 8, Aug. 2020, pp. 930–39. Pubmed, doi:10.1002/mc.23208.
Liu X, Qian D, Liu H, Abbruzzese JL, Luo S, Walsh KM, Wei Q. Genetic variants of the peroxisome proliferator-activated receptor (PPAR) signaling pathway genes and risk of pancreatic cancer. Mol Carcinog. 2020 Aug;59(8):930–939.
Journal cover image

Published In

Mol Carcinog

DOI

EISSN

1098-2744

Publication Date

August 2020

Volume

59

Issue

8

Start / End Page

930 / 939

Location

United States

Related Subject Headings

  • Survival Rate
  • Quantitative Trait Loci
  • Protein Kinase C-alpha
  • Protein Kinase C beta
  • Prognosis
  • Polymorphism, Single Nucleotide
  • Peroxisome Proliferator-Activated Receptors
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • Middle Aged