Association of TNF‐a (rs361525 and rs1800629) with susceptibility to cervical intraepithelial lesion and cervical carcinoma in women from Republic of North Macedonia

Abstract

Cervical cancer (CCa) is one of the most common malign diseases in women associated with human papillomavirus (HPV). The virus is an initiating factor, but not sufficient for the development of cervical intraepithelial lesions (CIN) and CCa. The disease might be a result of the influence of host's genetic factors and polymorphisms in inflammatory‐related genes that modify the immune response to HPV and attribute to cancer susceptibility. We carried out a study to determine the association between TNF‐a‐238G/A and TNF‐a‐308 G/T polymorphisms with HPV‐positive CIN and CCa in women living in the Republic of North Macedonia. Using multiplex SNaPshot analysis for single nucleotide polymorphisms (SNPs), we analysed the genotype and allele distributions of TNF‐a‐238G/A and TNF‐a‐308 G/T in 134 cases (HPV‐positive and histologically confirmed CIN and CCa) and in 113 controls (cytological and HPV‐negative women). For further analysis, the case group was stratified in three subgroups (all cases: CINs+ CCa− group; CIN2+ ‐group and CIN1− group). Data analysed using the odds ratio (OR) and chi‐square test showed the frequency of AA genotypes and A alleles are not significantly higher in cases compared to the controls for both SNPs: AA of TNF‐a‐238 (0.7% versus 0%) and TNF‐a‐308 (1.5% versus 0.9%) as well as A allelic frequency (3.0% versus 1.7%) and (13.1% versus 10.6), respectively. The comparison of the case's subgroups with the control group did not show a statistically significant difference. Compared to controls, TNF‐a‐238G/A and TNF‐a‐308 G/T are not associated with the risk of HPV associated CIN or CCa in the studied women.

A Meta-Analysis for Association of XRCC3 rs861539, MTHFR rs1801133, IL-6 rs1800795, IL-12B rs3212227, TNF-α rs1800629, and TLR9 rs352140 Polymorphisms with Susceptibility to Cervical Carcinoma

“…Behboodi et al, (2021) in a study among 153 Iranian cervical cancer cases and 292 free cancer subjects demonstrated that TNF-α rs1800629 was associated with increased level and risk of developing cervical cancer. However, Duvlis et al, (2020) reported that TNF-a-238G/A and TNF-a-308 G/T polymorphisms were not associated with the risk of HPV associated cervical intraepithelial lesions or cervical cancer cases in Macedonian women compared to controls. Moreover, Traore et al, (2020) revealed that TNF-308 G/A or IL18-607C/A polymorphisms were not associated with HPV infection among Burkina Faso women.…”

The Association of TNF-α Promoter Polymorphisms with Genetic Susceptibility to Cervical Cancer in a Chinese Han Population

“…Nevertheless, the results of associations between TNF-α polymorphisms and cervical cancer are still controversial in different populations, even the same population. [6][7][8][9][10][11][12][13][14][15] For example, in 2001, Jang et al reported that the rs361525 A allele is a protective factor for cervical cancer in a Korean population. 13 In 2018, Li et al reported that the rs361525 A allele is a risk factor for cervical squamous cell carcinoma in a Chinese population from Shandong Province, Northern China.…”