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Potential functional variants in SMC2 and TP53 in the AURORA pathway genes and risk of pancreatic cancer.

Publication ,  Journal Article
Feng, Y; Liu, H; Duan, B; Liu, Z; Abbruzzese, J; Walsh, KM; Zhang, X; Wei, Q
Published in: Carcinogenesis
June 10, 2019

The AURORA pathway participates in mitosis and cell division, and alterations in mitosis and cell division can lead to carcinogenesis. Therefore, genetic variants in the AURORA pathway genes may be associated with susceptibility to pancreatic cancer. To test this hypothesis, we used three large publically available pancreatic cancer genome-wide association study (GWAS) datasets (PanScan I, II/III and PanC4) to assess the associations of 7168 single nucleotide polymorphisms (SNPs) in a set of 62 genes of this pathway with pancreatic cancer risk in 8477 cases and 6946 controls of European ancestry. We identify 15 significant pancreatic cancer risk-associated SNPs in three genes (SMC2, ARHGEF7 and TP53) after correction for multiple comparisons by a false discovery rate < 0.20. Through further linkage disequilibrium analysis, SNP functional prediction and stepwise logistic regression analysis, we focused on three SNPs: rs3818626 in SMC2, rs79447092 in ARHGEF7 and rs9895829 in TP53. We found that these three SNPs were associated with pancreatic cancer risk [odds ratio (OR) = 1.12, 95% confidence interval (CI) = 1.07-1.17 and P = 2.20E-06 for the rs3818626 C allele; OR = 0.76, CI = 0.66-0.88 and P = 1.46E-04 for the rs79447092 A allele and OR = 0.82, CI = 0.74-0.91 and P = 1.51E-04 for the rs9895829 G allele]. Their joint effect as the number of protective genotypes also showed a significant association with pancreatic cancer risk (trend test P ≤ 0.001). Finally, we performed an expression quantitative trait loci analysis and found that rs3818626 and rs9895829 were significantly associated with SMC2 and TP53 messenger RNA expression levels in 373 lymphoblastoid cell lines, respectively. In conclusion, these three representative SNPs may be potentially susceptibility loci for pancreatic cancer and warrant additional validation.

Duke Scholars

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Published In

Carcinogenesis

DOI

EISSN

1460-2180

Publication Date

June 10, 2019

Volume

40

Issue

4

Start / End Page

521 / 528

Location

England

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Risk
  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Pancreatic Neoplasms
  • Pancreas
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Linkage Disequilibrium
 

Citation

APA
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Feng, Y., Liu, H., Duan, B., Liu, Z., Abbruzzese, J., Walsh, K. M., … Wei, Q. (2019). Potential functional variants in SMC2 and TP53 in the AURORA pathway genes and risk of pancreatic cancer. Carcinogenesis, 40(4), 521–528. https://doi.org/10.1093/carcin/bgz029
Feng, Yun, Hongliang Liu, Bensong Duan, Zhensheng Liu, James Abbruzzese, Kyle M. Walsh, Xuefeng Zhang, and Qingyi Wei. “Potential functional variants in SMC2 and TP53 in the AURORA pathway genes and risk of pancreatic cancer.Carcinogenesis 40, no. 4 (June 10, 2019): 521–28. https://doi.org/10.1093/carcin/bgz029.
Feng Y, Liu H, Duan B, Liu Z, Abbruzzese J, Walsh KM, et al. Potential functional variants in SMC2 and TP53 in the AURORA pathway genes and risk of pancreatic cancer. Carcinogenesis. 2019 Jun 10;40(4):521–8.
Feng, Yun, et al. “Potential functional variants in SMC2 and TP53 in the AURORA pathway genes and risk of pancreatic cancer.Carcinogenesis, vol. 40, no. 4, June 2019, pp. 521–28. Pubmed, doi:10.1093/carcin/bgz029.
Feng Y, Liu H, Duan B, Liu Z, Abbruzzese J, Walsh KM, Zhang X, Wei Q. Potential functional variants in SMC2 and TP53 in the AURORA pathway genes and risk of pancreatic cancer. Carcinogenesis. 2019 Jun 10;40(4):521–528.
Journal cover image

Published In

Carcinogenesis

DOI

EISSN

1460-2180

Publication Date

June 10, 2019

Volume

40

Issue

4

Start / End Page

521 / 528

Location

England

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Risk
  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Pancreatic Neoplasms
  • Pancreas
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Linkage Disequilibrium