Tumor Necrosis Factor Alpha (-238 / -308) and TNFRII-VNTR (-322) Polymorphisms as Genetic Biomarkers of Susceptibility to Develop Cervical Cancer Among Tunisians

Pathol Oncol Res. 2015 Apr;21(2):339-45. doi: 10.1007/s12253-014-9826-2. Epub 2014 Aug 12.

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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Biomarkers, Tumor / genetics*
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease / ethnology
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Haplotypes / genetics
  • Heterozygote
  • Humans
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Receptors, Tumor Necrosis Factor, Type II / genetics*
  • Risk Factors
  • Tumor Necrosis Factor-alpha / genetics*
  • Tunisia / epidemiology
  • Uterine Cervical Neoplasms / epidemiology
  • Uterine Cervical Neoplasms / ethnology
  • Uterine Cervical Neoplasms / genetics*

Substances

  • Biomarkers, Tumor
  • Receptors, Tumor Necrosis Factor, Type II
  • Tumor Necrosis Factor-alpha