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Associations of novel variants in PIK3C3, INSR and MAP3K4 of the ATM pathway genes with pancreatic cancer risk.

Publication ,  Journal Article
Zhao, L-L; Liu, H-L; Luo, S; Walsh, KM; Li, W; Wei, Q
Published in: Am J Cancer Res
2020

The ATM serine/threonine kinase (ATM) pathway plays important roles in pancreatic cancer (PanC) development and progression, but the roles of genetic variants of the genes in this pathway in the etiology of PanC are unknown. In the present study, we assessed associations between 31,499 single nucleotide polymorphisms (SNPs) in 198 ATM pathway-related genes and PanC risk using genotyping data from two previously published PanC genome-wide association studies (GWASs) of 15,423 subjects of European ancestry. In multivariable logistic regression analysis, we identified three novel independent SNPs to be significantly associated with PanC risk [PIK3C3 rs76692125 G>A: odds ratio (OR)=1.26, 95% confidence interval (CI)=1.12-1.43 and P=2.07×10-4, INSR rs11668724 G>A: OR=0.89, 95% CI=0.84-0.94 and P=4.21×10-5 and MAP3K4 rs13207108 C>T: OR=0.83, 95% CI=0.75-0.92, P=2.26×10-4]. The combined analysis of these three SNPs exhibited an increased PanC risk in a dose-response manner as the number of unfavorable genotypes increased (P trend<0.0001). The risk-associated rs76692125 A allele was correlated with decreased PIK3C3 mRNA expression levels, while the protective-associated rs11668724 A allele was correlated with increased INSR mRNA expression levels, but additional mechanistic studies of these SNPs are warranted. Once validated, these SNPs may serve as biomarkers for PanC risk in populations of European ancestry.

Duke Scholars

Published In

Am J Cancer Res

ISSN

2156-6976

Publication Date

2020

Volume

10

Issue

7

Start / End Page

2128 / 2144

Location

United States

Related Subject Headings

  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis
 

Citation

APA
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MLA
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Zhao, L.-L., Liu, H.-L., Luo, S., Walsh, K. M., Li, W., & Wei, Q. (2020). Associations of novel variants in PIK3C3, INSR and MAP3K4 of the ATM pathway genes with pancreatic cancer risk. Am J Cancer Res, 10(7), 2128–2144.
Zhao, Ling-Ling, Hong-Liang Liu, Sheng Luo, Kyle M. Walsh, Wei Li, and Qingyi Wei. “Associations of novel variants in PIK3C3, INSR and MAP3K4 of the ATM pathway genes with pancreatic cancer risk.Am J Cancer Res 10, no. 7 (2020): 2128–44.
Zhao L-L, Liu H-L, Luo S, Walsh KM, Li W, Wei Q. Associations of novel variants in PIK3C3, INSR and MAP3K4 of the ATM pathway genes with pancreatic cancer risk. Am J Cancer Res. 2020;10(7):2128–44.
Zhao, Ling-Ling, et al. “Associations of novel variants in PIK3C3, INSR and MAP3K4 of the ATM pathway genes with pancreatic cancer risk.Am J Cancer Res, vol. 10, no. 7, 2020, pp. 2128–44.
Zhao L-L, Liu H-L, Luo S, Walsh KM, Li W, Wei Q. Associations of novel variants in PIK3C3, INSR and MAP3K4 of the ATM pathway genes with pancreatic cancer risk. Am J Cancer Res. 2020;10(7):2128–2144.

Published In

Am J Cancer Res

ISSN

2156-6976

Publication Date

2020

Volume

10

Issue

7

Start / End Page

2128 / 2144

Location

United States

Related Subject Headings

  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis