Characterization of Single-Nucleotide Polymorphisms in the Tumor Necrosis Factor α Promoter Region and in Lymphotoxin α in Squamous Intraepithelial Lesions, Precursors of Cervical Cancer

Abstract

Development of cervical cancer is a long process of abnormal cancerous cell growth in the cervix and is primarily the result of infection with specific high-risk types of human papillomavirus (HPV). The cytokines tumor necrosis factor α (TNFα) and lymphotoxin α (LTA) have an important role in all stages of cervical cancer and have the ability to induce the regression or promote the development of human tumors. Biologically important single-nucleotide polymorphisms (SNPs) occur within the TNFα and LTA genes. Therefore, the purpose of this study was to investigate the SNPs in the TNFα promoter region (-163, -238, -244, -308, -376, -857, -863, and -1031) and in the first intron of LTA (+252) in women with precursor lesions of cervical cancer. Overall, we studied 396 women from Mexico City. A total of 191 patients with HPV infection and precursor cervical lesions were subdivided in two groups: those with low-grade squamous intraepithelial lesions (n = 132) and those with high-grade squamous intraepithelial lesions (n = 59). Women (n = 205) negative for HPV and without cervical lesions were also included in the study. DNA was extracted from peripheral white blood cells and from cervical samples, and detection of biallelic polymorphisms of TNFα and LTA was performed using the polymerase chain reaction-sequence-specific oligonucleotide probe and restriction fragment length polymorphism techniques, respectively. We demonstrated that risk is associated with the genotype G/A (odds ratio = 2.48) and that protection is associated with the genotype G/G of SNP TNFα -376 (odds ratio = 0.37).

The Association of Serum TNF-α Levels and Blood Multi-Elements Modified by TNF-α Gene Polymorphisms in Metal Industrial Workers

“…TNF-α −238 and −308 SNPs are two of the most extensively studied polymorphisms in many diseases [20,21,22]. The genotype GG is the most frequent in both SNPs in various ethnic groups [23,24], which is consistent with our findings. In our study, we proposed that TNF-α −238 G/A might be a protective genotype and −308A/A might be a susceptible genotype.…”

The Correlation Between TNF-α Promoter Gene Polymorphism and Genetic Susceptibility to Cervical Cancer

“… 36 In Mexican, a study found that rs1800750 polymorphism was protective for intraepithelial neoplasia, and rs1799964 and rs673 were neutral. 25 …”

Three polymorphisms of tumor necrosis factor-alpha and hepatitis B virus related hepatocellular carcinoma

“…Literature has shown that several functional SNPs in the TNF-α promoter region were reported to influence the TNF-α constitutive and inducible expression levels. [ 44 , 45 ]…”