Abstract
Host genetic factors may confer susceptibility to Cervical Cancer. TNF-alpha 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-alpha-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 TNF alpha-238 G > A and TNF alpha-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-alpha 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-alpha and TNFRII polymorphisms might be genetic risk factors for cervical cancer inTunisian population.