title: Tumor Necrosis Factor Alpha (-238 / -308) and TNFRII-VNTR (-322) Polymorphisms as Genetic Biomarkers of Susceptibility to Develop Cervical Cancer Among Tunisians.
abstract: Host genetic factors may confer susceptibility to Cervical Cancer. TNF-α as pro-inflammatory cytokine participates in the maintenance of immune homeostasis. Allelic variation of immuno-modulatory genes is associated with alteration in immune function. This study investigated the associations between TNF-α-308G>A, -238G>A, and TNFRII - VNTR-322 and cervical cancer in Tunisian women. Genotypes of those polymorphisms were detected in 130 cases and 260 controls. The variant heterozygote -308 G/A was associated with a 41% decreased risk of cervical cancer (GG vs A/A; p = 0.002; OR = 0.41; 95% CI =0.23-0.76). Furthermore, compared with dominant variant G/G, the (G/A+A/A) genotypes was significantly associated with a decreased risk of CC (GG vs G/A+A/A; p = 0.026; OR = 0.62; 95% CI = 0.40-0.97). The FIGO stratified analysis showed that the minor variant A/A and combined G/A+A/A of TNFα-238 G>A and TNFα-308 G>A increased the risk of the tumor evolution, respectively, (P = 0.011; OR = 2.98; 95% CI = 1.16-7.72) (P = 0.008; OR = 2.76; 95% CI = 1.20-6.41), (P = 0.000; OR = 16.33; 95% CI = (5.10-55.23) (P = 0.000; OR = 7.54; 95% CI = 2.68-22.29). There was statistically significant relationship between the incidence of the TNF-α mutations and the clinical progression of cancer according to the FIGO classification. In our study, the haploview analysis revealed no LD between rs1800629 and rs361525. TNF-α and TNFRII polymorphisms might be genetic risk factors for cervical cancer in Tunisian population.
authors.affiliation: Faculty of Sciences of Tunis, Laboratory of Micro-Organisms and Active Biomolecules, El Manar University, 2092 El MANAR I, 1092, Tunis, Tunisia, ZIDISABRINA86@gmail.com.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Zidi
authors.forename: Mouna
authors.initials: M
authors.lastname: Stayoussef
authors.forename: Ferjeni
authors.initials: F
authors.lastname: Zouidi
authors.forename: Samir
authors.initials: S
authors.lastname: Benali
authors.forename: Ezzedine
authors.initials: E
authors.lastname: Gazouani
authors.forename: Amel
authors.initials: A
authors.lastname: Mezlini
authors.forename: Besma
authors.initials: B
authors.lastname: Yacoubi-Loueslati
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics*; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D014416:Tunisia / Q000453:epidemiology; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha
references.citation: Ann Med. 2011 Mar;43(2):90-103
references.pmid: 21039303
references.citation: J Infect Dis. 2009 Jan 1;199(1):20-30
references.pmid: 19012493
references.citation: CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90
references.pmid: 21296855
references.citation: J Immunol. 1996 Sep 1;157(5):2155-9
references.pmid: 8757341
references.citation: Gynecol Oncol. 2003 Mar;88(3):326-32
references.pmid: 12648582
references.citation: Cancer Res. 2003 Aug 1;63(15):4375-83
references.pmid: 12907607
references.citation: Cell Oncol. 2007;29(3):249-56
references.pmid: 17452777
references.citation: Cancer Invest. 1998;16(3):152-9
references.pmid: 9541628
references.citation: Cancer Genet Cytogenet. 2004 Apr 15;150(2):116-21
references.pmid: 15066318
references.citation: Nucleic Acids Res. 1994 Mar 25;22(6):1108-14
references.pmid: 8152914
references.citation: Gynecol Oncol. 2012 Aug;126(2):304-11
references.pmid: 22484226
references.citation: J Infect Dis. 2005 Mar 15;191(6):969-76
references.pmid: 15717274
references.citation: J Clin Invest. 1993 May;91(5):2194-206
references.pmid: 8387543
references.citation: J Clin Virol. 2012 Jan;53(1):54-9
references.pmid: 22019249
references.citation: Tumour Biol. 2013 Jun;34(3):1659-65
references.pmid: 23494178
references.citation: BMC Cancer. 2006 Jan 26;6:24
references.pmid: 16438713
references.citation: J Infect Dis. 1993 May;167(5):1168-72
references.pmid: 8486950
references.citation: Hum Reprod. 2004 Nov;19(11):2509-14
references.pmid: 15319381
references.citation: Clin Chem. 2002 Aug;48(8):1218-24
references.pmid: 12142377
references.citation: Asian Pac J Cancer Prev. 2012;13(11):5777-83
references.pmid: 23317256
references.citation: Cancer Lett. 2001 May 10;166(1):41-6
references.pmid: 11295285
references.citation: J Reprod Immunol. 1998 Jul;38(2):123-38
references.pmid: 9730287
references.citation: Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3195-9
references.pmid: 9096369
references.citation: N Engl J Med. 1996 Jun 27;334(26):1717-25
references.pmid: 8637518
references.citation: PLoS One. 2012;7(9):e45246
references.pmid: 23028877
references.citation: Eur Cytokine Netw. 2011 Jun;22(2):88-102
references.pmid: 21768061
references.citation: Biochem Pharmacol. 2003 Oct 15;66(8):1403-8
references.pmid: 14555214
references.citation: Genes Immun. 1999 Nov;1(2):164-5
references.pmid: 11196666
references.citation: Virology. 2010 May 25;401(1):70-9
references.pmid: 20206957
references.citation: Int J Gynecol Cancer. 2012 Feb;22(2):213-9
references.pmid: 22146770
references.citation: Cancer Biol Ther. 2011 Feb 1;11(3):295-306
references.pmid: 21239888
references.citation: Scand J Immunol. 2011 Dec;74(6):522-47
references.pmid: 21790707
references.citation: Int J Gynecol Cancer. 2003 Mar-Apr;13(2):148-53
references.pmid: 12657115
references.citation: Nat Rev Drug Discov. 2008 May;7(5):411-25
references.pmid: 18404150
references.citation: Cancer Genet Cytogenet. 2005 Jun;159(2):143-7
references.pmid: 15899386
references.citation: Nat Rev Cancer. 2004 Jan;4(1):11-22
references.pmid: 14708024
references.citation: Lancet. 2001 Feb 17;357(9255):539-45
references.pmid: 11229684
references.citation: Blood. 2001 Aug 15;98(4):1108-15
references.pmid: 11493458
references.citation: Hum Mol Genet. 2002 May 15;11(11):1281-9
references.pmid: 12019209
references.citation: Expert Opin Biol Ther. 2011 Oct;11(10):1341-59
references.pmid: 21651458
references.citation: Tumour Biol. 2012 Oct;33(5):1549-56
references.pmid: 22592655
references.citation: J Inflamm. 1995;45(1):1-12
references.pmid: 7583349
references.citation: Proc Natl Acad Sci U S A. 1990 Feb;87(3):1233-7
references.pmid: 2105500
references.citation: J Biol Regul Homeost Agents. 1992 Jul-Sep;6(3):103-7
references.pmid: 1492596
references.citation: Biochem Biophys Res Commun. 2005 Aug 26;334(2):588-92
references.pmid: 16009345
references.citation: Oncogene. 2008 Nov 24;27(55):7018-30
references.pmid: 19029942
references.citation: Mol Biol Rep. 2012 Mar;39(3):2683-8
references.pmid: 21670964
references.citation: Clin Biochem. 2001 Sep;34(6):491-8
references.pmid: 11676979
references.citation: Immunol Rev. 2011 Nov;244(1):99-114
references.pmid: 22017434
references.citation: Transpl Immunol. 1999 Jun;7(2):127-8
references.pmid: 10544444