Generic placeholder image

Current Molecular Medicine


ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Research Article

Association of ATG7 Polymorphisms and Clear Cell Renal Cell Carcinoma Risk

Author(s): Zhenlong Wang, Lei Tao, Yuquan Xue, Li Xue, Ziming Wang* and Tie Chong*

Volume 19 , Issue 1 , 2019

Page: [40 - 47] Pages: 8

DOI: 10.2174/1566524019666190227202003

Price: $65


Background: Kidney cancer is one of the most common cancers worldwide. Recent studies have suggested that single nucleotide polymorphisms (SNPs) in autophagy-related gene are associated with the risk of kidney cancer.

Objective: This study was undertaken to investigate the association of autophagyrelated gene 7 (ATG7) polymorphisms with the risk of clear cell renal cell carcinoma (ccRCC) in the Chinese Han population.

Methods: Blood samples were collected from 293 ccRCC patients and 297 healthy controls. Three ATG7 polymorphisms (rs1375206, rs2606736 and rs6442260) were genotyped by Agena MassARRAY. The association was estimated by genetic models and stratification analyses.

Results: A significant association was observed between allele A of rs6442260 and ccRCC risk (OR = 0.76, 95% CI: 0.58-0.99, p = 0.039). Genetic model analysis revealed that rs2606736 (OR = 0.57, 95% CI: 0.34-0.95, p = 0.031) and rs6442260 (OR = 0.44, 95% CI: 0.22-0.90, p = 0.021) were associated with decreased risk of ccRCC under recessive model. Age stratification analysis showed that rs2606736 (OR = 0.67, 95% CI: 0.46-0.98, p = 0.036) and rs6442260 (OR = 0.26, 95% CI: 0.07-0.89, p = 0.014) were significantly decreased risk of ccRCC under the log-additive model in age > 55 years old and ≤ 55 years old, respectively.

Conclusions: This study indicated that ATG7 polymorphisms (rs2606736 and rs6442260) have a protective role for ccRCC risk. Further large sample size and functional assays are needed to confirm our findings and reveal the role of ATG7 polymorphisms in ccRCC carcinogenesis.

Keywords: ATG7, Polymorphisms, Clear cell renal cell carcinoma, Chinese Han, Case-control, SNPs.

Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017 [J]. CA Cancer J Clin 2017; 67(1): 7-30.
Ljungberg B, Campbell SC, Choi HY, et al. The epidemiology of renal cell carcinoma [J]. Eur Urol 2011; 60(4): 615-21.
Hsieh JJ, Purdue MP, Signoretti S, et al. Renal cell carcinoma [J]. Nat Rev Dis Primers 2017; 3: 17009.
Mclaughlin JK, Lipworth L, Tarone RE. Epidemiologic aspects of renal cell carcinoma [J]. Semin Oncol 2006; 33(5): 527-33.
Chow WH, Dong LM, Devesa SS. Epidemiology and risk factors for kidney cancer [J]. Nat Rev Urol 2010; 7(5): 245-57.
Tizaoui K, Hamzaoui K, Hamzaoui A. Update on Asthma Genetics: Results From Meta-Analyses of Candidate Gene Association Studies [J]. Curr Mol Med 2017; 17(10): 647-67.
Huang XF, Chi W, Lin D, et al. Association of IL33 and IL1RAP Polymorphisms With Acute Anterior Uveitis [J]. Curr Mol Med 2018; 17(7): 471-7.
Pan X, Zheng M, Zou T, et al. The LEPR K109R and Q223R Might Contribute to the Risk of NAFLD: A Meta-Analysis [J]. Curr Mol Med 2018; 18(2): 91-9.
Liu XD, Yao J, Tripathi DN, et al. Autophagy mediates HIF2alpha degradation and suppresses renal tumorigenesis [J]. Oncogene 2015; 34(19): 2450-60.
Yu Z, Ma J, Li X, et al. Autophagy defects and related genetic variations in renal cell carcinoma with eosinophilic cytoplasmic inclusions [J]. Sci Rep 2018; 8(1): 9972.
Tanida I, Mizushima N, Kiyooka M, et al. Apg7p/Cvt2p: A novel protein-activating enzyme essential for autophagy [J]. Mol Biol Cell 1999; 10(5): 1367-79.
Komatsu M, Wang QJ, Holstein GR, et al. Essential role for autophagy protein Atg7 in the maintenance of axonal homeostasis and the prevention of axonal degeneration [J]. Proc Natl Acad Sci USA 2007; 104(36): 14489-94.
Mortensen M, Simon AK. Nonredundant role of Atg7 in mitochondrial clearance during erythroid development [J]. Autophagy 2010; 6(3): 423-5.
Zhang Y, Goldman S, Baerga R, et al. Adipose-specific deletion of autophagy-related gene 7 (atg7) in mice reveals a role in adipogenesis [J]. Proc Natl Acad Sci USA 2009; 106(47): 19860-5.
Mortensen M, Soilleux EJ, Djordjevic G, et al. The autophagy protein Atg7 is essential for hematopoietic stem cell maintenance [J]. J Exp Med 2011; 208(3): 455-67.
Turcotte S, Chan DA, Sutphin PD, et al. A molecule targeting VHL-deficient renal cell carcinoma that induces autophagy [J]. Cancer Cell 2008; 14(1): 90-102.
Liu XD, Yao J, Tripathi DN, et al. Autophagy mediates HIF2α degradation and suppresses renal tumorigenesis [J]. Oncogene 2015; 34(19): 2450-60.
Sole X, Guino E, Valls J, et al. SNPStats: a web tool for the analysis of association studies [J]. Bioinformatics 2006; 22(15): 1928-9.
Chandrashekar DS, Bashel B. Balasubramanya SaH, UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses [J]. Neoplasia 2017; 19(8): 649-58.
Tang Z, Li C, Kang B, et al. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses [J]. Nucleic Acids Res 2017; 45(W1): W98-W102.
Mizushima N. Autophagy: process and function [J]. Genes Dev 2007; 21(22): 2861-73.
Brest P, Corcelle EA, Cesaro A, et al. Autophagy and Crohn’s disease: at the crossroads of infection, inflammation, immunity, and cancer [J]. Curr Mol Med 2010; 10(5): 486-502.
Zhao X, Gao S, Ren H, et al. Inhibition of autophagy strengthens celastrol-induced apoptosis in human pancreatic cancer in vitro and in vivo models [J]. Curr Mol Med 2014; 14(4): 555-63.
Amaravadi R, Kimmelman AC, White E. Recent insights into the function of autophagy in cancer [J]. Genes Dev 2016; 30(17): 1913-30.
Eskelinen EL. The dual role of autophagy in cancer [J]. Curr Opin Pharmacol 2011; 11(4): 294-300.
Yun CW, Lee SH. The Roles of Autophagy in Cancer [J]. Int J Mol Sci 2018; 19(11)
Sandra T, Chan DA, Sutphin PD, et al. A molecule targeting VHL-deficient renal cell carcinoma that induces autophagy [J]. Cancer Cell 2008; 14(1): 90-102.
Singla M, Bhattacharyya S. Autophagy as a potential therapeutic target during epithelial to mesenchymal transition in renal cell carcinoma: An in vitro study [J]. Biomed Pharmacother 2017; 94: 332-40.
Tanida I, Tanida-Miyake E, Ueno T, et al. The human homolog of Saccharomyces cerevisiae Apg7p is a Protein-activating enzyme for multiple substrates including human Apg12p, GATE-16, GABARAP, and MAP-LC3 [J]. J Biol Chem 2001; 276(3): 1701-6.
Noda NN, Inagaki F. Mechanisms of Autophagy [J]. Annu Rev Biophys 2015; 44: 101-22.
Sun S, Wang Z, Tang F, et al. ATG7 promotes the tumorigenesis of lung cancer but might be dispensable for prognosis predication: a clinicopathologic study [J]. OncoTargets Ther 2016; 9: 4975-81.
Santanam U, Banach-Petrosky W, Abate-Shen C, et al. Atg7 cooperates with Pten loss to drive prostate cancer tumor growth [J]. Genes Dev 2016; 30(4): 399-407.
Zhu J, Li Y, Tian Z, et al. ATG7 Overexpression Is Crucial for Tumorigenic Growth of Bladder Cancer In Vitro and In Vivo by Targeting the ETS2/miRNA196b/FOXO1/p27 Axis [J]. Mol Ther Nucleic Acids 2017; 7: 299-313.
Wang ZL, Deng Q, Chong T, et al. Autophagy suppresses the proliferation of renal carcinoma celln [J]. Eur Rev Med Pharmacol Sci 2018; 22(2): 343-50.
Christie S, Robiou-Du-Pont S, Anand SS, et al. Genetic contribution to lipid levels in early life based on 158 loci validated in adults: the FAMILY study [J]. Sci Rep 2017; 7(1): 68.
Van Hemelrijck M, Garmo H, Hammar N, et al. The interplay between lipid profiles, glucose, BMI and risk of kidney cancer in the Swedish AMORIS study [J]. Int J Cancer 2012; 130(9): 2118-28.
Pham DL, Kim SH, Losol P, et al. Association of autophagy related gene polymorphisms with neutrophilic airway inflammation in adult asthma [J]. Korean J Intern Med 2016; 31(2): 375-85.
Bi LK, Zhou N, Liu C, et al. Kidney cancer cells secrete IL-8 to activate Akt and promote migration of mesenchymal stem cells [J]. Urol Oncol 2014; 32(5): 607-12.

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy