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Potentially functional genetic variants in PLIN2, SULT2A1 and UGT1A9 genes of the ketone pathway and survival of nonsmall cell lung cancer.

Publication ,  Journal Article
Tang, D; Zhao, YC; Liu, H; Luo, S; Clarke, JM; Glass, C; Su, L; Shen, S; Christiani, DC; Gao, W; Wei, Q
Published in: Int J Cancer
September 15, 2020

The ketone metabolism pathway is a principle procedure in physiological homeostasis and induces cancer cells to switch between glycolysis and oxidative phosphorylation for energy production. We conducted a two-phase analysis for associations between genetic variants in the ketone metabolism pathway genes and survival of nonsmall cell lung cancer (NSCLC) by analyzing genotyping data from two published genome-wide association studies (GWASs). In the discovery, we used a genotyping dataset from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial in the multivariable Cox proportional hazards regression analysis. We used Bayesian false discovery probability (≤0.80) for multiple testing correction to evaluate associations between 25,819 (2,176 genotyped and 23,643 imputed) single-nucleotide polymorphisms (SNPs) in 162 genes and survival of 1,185 NSCLC patients. Subsequently, we validated the identified significant SNPs with an additional 984 NSCLC patients from the Harvard Lung Cancer Susceptibility GWAS study. Finally, we found that three independent and potentially functional SNPs in three different genes (i.e., PLIN2 rs7867814 G>A, SULT2A1 rs2547235 C>T and UGT1A9 rs2011404 C>T) were independently associated with risk of death from NSCLC, with a combined hazards ratio of 1.22 [95% confidence interval = 1.09-1.36 and p = 0.0003], 0.82 (0.74-0.91 and p = 0.0002) and 1.21 (1.10-1.33 and p = 0.0001), respectively. Additional expression quantitative trait loci analysis found that the survival-associated PLIN2 rs7867814 GA + AA genotypes, but not the genotypes of other two SNPs, were significantly associated with increased mRNA expression levels (p = 0.005). These results indicated that PLIN2 variants may be potential predictors of NSCLC survival through regulating the PLIN2 expression.

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Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

September 15, 2020

Volume

147

Issue

6

Start / End Page

1559 / 1570

Location

United States

Related Subject Headings

  • UDP-Glucuronosyltransferase 1A9
  • Survival Analysis
  • Sulfotransferases
  • RNA, Messenger
  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Perilipin-2
  • Oncology & Carcinogenesis
  • Models, Genetic
  • Middle Aged
 

Citation

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Tang, D., Zhao, Y. C., Liu, H., Luo, S., Clarke, J. M., Glass, C., … Wei, Q. (2020). Potentially functional genetic variants in PLIN2, SULT2A1 and UGT1A9 genes of the ketone pathway and survival of nonsmall cell lung cancer. Int J Cancer, 147(6), 1559–1570. https://doi.org/10.1002/ijc.32932
Tang, Dongfang, Yu C. Zhao, Hongliang Liu, Sheng Luo, Jeffrey M. Clarke, Carolyn Glass, Li Su, et al. “Potentially functional genetic variants in PLIN2, SULT2A1 and UGT1A9 genes of the ketone pathway and survival of nonsmall cell lung cancer.Int J Cancer 147, no. 6 (September 15, 2020): 1559–70. https://doi.org/10.1002/ijc.32932.
Tang D, Zhao YC, Liu H, Luo S, Clarke JM, Glass C, et al. Potentially functional genetic variants in PLIN2, SULT2A1 and UGT1A9 genes of the ketone pathway and survival of nonsmall cell lung cancer. Int J Cancer. 2020 Sep 15;147(6):1559–70.
Tang, Dongfang, et al. “Potentially functional genetic variants in PLIN2, SULT2A1 and UGT1A9 genes of the ketone pathway and survival of nonsmall cell lung cancer.Int J Cancer, vol. 147, no. 6, Sept. 2020, pp. 1559–70. Pubmed, doi:10.1002/ijc.32932.
Tang D, Zhao YC, Liu H, Luo S, Clarke JM, Glass C, Su L, Shen S, Christiani DC, Gao W, Wei Q. Potentially functional genetic variants in PLIN2, SULT2A1 and UGT1A9 genes of the ketone pathway and survival of nonsmall cell lung cancer. Int J Cancer. 2020 Sep 15;147(6):1559–1570.
Journal cover image

Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

September 15, 2020

Volume

147

Issue

6

Start / End Page

1559 / 1570

Location

United States

Related Subject Headings

  • UDP-Glucuronosyltransferase 1A9
  • Survival Analysis
  • Sulfotransferases
  • RNA, Messenger
  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Perilipin-2
  • Oncology & Carcinogenesis
  • Models, Genetic
  • Middle Aged