title: Role of genetic variants of autophagy genes in susceptibility for non-medullary thyroid cancer and patients outcome.
abstract: Autophagy is a central process in regulation of cell survival, cell death and proliferation and plays an important role in carcinogenesis, including thyroid carcinoma. Genetic variation in autophagy components has been demonstrated to influence the capacity to execute autophagy and is associated with disease susceptibility, progression and outcome. In the present study, we assessed whether genetic variation in autophagy genes contributes to susceptibility to develop thyroid carcinoma, disease progression and/or patient outcome. The results indicate that patients carrying the ATG5 single nucleotide polymorphisms rs2245214 have a higher probability to develop thyroid carcinoma (OR 1.85 (95% CI 1.04-3.23), P = 0.042). In contrast, no significant differences could be observed for the other genetic variants studied in terms of thyroid carcinoma susceptibility. Furthermore, none of the selected genetic variants were associated with clinical parameters of disease progression and outcome. In conclusion, genetic variation in ATG5, a central player in the autophagy process, is found to be associated with increased susceptibility for thyroid carcinoma, indicating a role for autophagy in thyroid carcinogenesis.
authors.affiliation: Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands; Division of Endocrinology, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Theo S
authors.initials: TS
authors.lastname: Plantinga
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: van de Vosse
authors.affiliation: Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands; Division of Endocrinology, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Angelique
authors.initials: A
authors.lastname: Huijbers
authors.affiliation: Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.affiliation: Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
authors.affiliation: Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands; Division of Endocrinology, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Jan W A
authors.initials: JW
authors.lastname: Smit
authors.affiliation: Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands; Division of Endocrinology, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Romana T
authors.initials: RT
authors.lastname: Netea-Maier
mesh_terms: D000328:Adult; D001343:Autophagy / Q000235:genetics*; D000071187:Autophagy-Related Protein 5; D002277:Carcinoma / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016019:Survival Analysis; D013964:Thyroid Neoplasms / Q000235:genetics*
chemical_list: C502778:ATG5 protein, human; D000071187:Autophagy-Related Protein 5; D008869:Microtubule-Associated Proteins
references.citation: Nature. 2008 Nov 13;456(7219):264-8
references.pmid: 18849965
references.citation: Surgery. 2009 Dec;146(6):1208-14
references.pmid: 19958950
references.citation: Nat Rev Cancer. 2006 Apr;6(4):292-306
references.pmid: 16557281
references.citation: Inflamm Bowel Dis. 2011 Jun;17(6):1392-7
references.pmid: 21560199
references.citation: Nat Genet. 2009 Nov;41(11):1228-33
references.pmid: 19838195
references.citation: Mod Pathol. 2011 Apr;24 Suppl 2:S19-33
references.pmid: 21455198
references.citation: Nat Genet. 2007 Jul;39(7):830-2
references.pmid: 17554261
references.citation: CA Cancer J Clin. 2006 Mar-Apr;56(2):106-30
references.pmid: 16514137
references.citation: Neurosci Lett. 2013 Mar 22;538:49-53
references.pmid: 23384565
references.citation: J Endocrinol. 2011 Jul;210(1):105-15
references.pmid: 21478229
references.citation: Nat Immunol. 2009 May;10(5):461-70
references.pmid: 19381141
references.citation: PLoS One. 2012;7(4):e33454
references.pmid: 22536318
references.citation: Sci China Life Sci. 2014 Jan;57(1):59-68
references.pmid: 24369351
references.citation: Nat Rev Cancer. 2005 Sep;5(9):726-34
references.pmid: 16148885
references.citation: Endocr Relat Cancer. 2012 May 03;19(3):L15-8
references.pmid: 22302078
references.citation: Nat Genet. 2013 Apr;45(4):445-9, 449e1
references.pmid: 23435086
references.citation: Cancer Res. 2010 May 1;70(9):3431-4
references.pmid: 20424122
references.citation: PLoS Genet. 2011 Feb;7(2):e1001311
references.pmid: 21379322
references.citation: J Biol Chem. 2001 Sep 21;276(38):35243-6
references.pmid: 11477064
references.citation: Nat Rev Mol Cell Biol. 2009 Jul;10(7):458-67
references.pmid: 19491929
references.citation: Genes Dev. 2011 Mar 1;25(5):460-70
references.pmid: 21317241
references.citation: Nature. 2008 Feb 28;451(7182):1069-75
references.pmid: 18305538
references.citation: Surgery. 2012 Dec;152(6):1142-9
references.pmid: 23158184
references.citation: J Biol Chem. 2011 Apr 15;286(15):12924-32
references.pmid: 21300795
references.citation: J Invest Dermatol. 2010 Jun;130(6):1657-67
references.pmid: 20182446
references.citation: Cell. 2005 Jan 28;120(2):159-62
references.pmid: 15680321
references.citation: Nat Genet. 2007 May;39(5):596-604
references.pmid: 17435756
references.citation: J Pathol. 2010 May;221(1):3-12
references.pmid: 20225336
references.citation: Cell Host Microbe. 2008 Nov 13;4(5):458-69
references.pmid: 18996346
references.citation: PLoS Pathog. 2009 Sep;5(9):e1000577
references.pmid: 19750224
references.citation: Mol Cancer Res. 2010 Sep;8(9):1217-26
references.pmid: 20736296
references.citation: Endocr Relat Cancer. 2013 Dec 16;21(1):R13-29
references.pmid: 24163390
references.citation: Autophagy. 2012 Sep;8(9):1387-8
references.pmid: 22885761
references.citation: Curr Opin Pharmacol. 2012 Aug;12(4):497-502
references.pmid: 22342166
references.citation: J Neuroendocrinol. 2008 Oct;20(10):1165-75
references.pmid: 18673414
references.citation: Nat Rev Mol Cell Biol. 2013 Dec;14(12):759-74
references.pmid: 24201109
references.citation: CA Cancer J Clin. 2013 Jan;63(1):11-30
references.pmid: 23335087