Laboratorio de Biología Molecular Aplicada, Facultad de Ciencias Exactas, Quimicas y Naturales, Universidad Nacional de Misiones, Av. Mariano Moreno 1375, Posadas, Misiones, Argentina.
J Clin Virol. 2012 Jan;53(1):54-9. doi: 10.1016/j.jcv.2011.09.030. Epub 2011 Oct 22.
Human papillomavirus (HPV) plays a central role in cervical cancer development. However, only a small fraction of infected women develop the disease. Additional risk factors, including SNPs in immune system and cytokine genes, are likely to be important determinants.
We investigated the potential role of cytokine TNF-α promoter SNPs (TNFα-375A, TNFα-307A, TNFα-243A, and TNFα-237A) in the development of high-grade cervical lesions and cancer in urban women from Posadas (Misiones, Argentina).
Fifty-six cases (CINIII and invasive carcinoma) and 113 age-matched controls were included in the study. HPV genotype detection was conducted by PCR. TNFα SNP genotyping was conducted through PCR amplification and direct sequencing of genomic DNA.
We observed differences in the allelic distribution of TNFα-307A and TNFα-375A SNPs among cases and controls (p<0.05). The TNFα-307A variant was associated with cervical cancer at an OR 2.4 (CI 95% 1.1-5.4), while the TNFα-375A SNP was identified in 8.8% of the controls and none of the cases. Moreover, the TNFα-375A always occurred in association with the TNFα-237A SNP, indicating linkage disequilibrium between them.
Our study suggests that the presence of the high producer allele TNFα-307A is associated with an increased risk for the development of cervical cancer in the Posadas population. We also speculate that the "protective effect" of the TNFα-375A/-237A haplotype, which was restricted to controls, may be related to HLA genes linked on chromosome 6. These findings contribute to our understanding of immune gene variation in an Argentinean population, and its role in disease susceptibility.
人乳头瘤病毒（HPV）在宫颈癌的发展中起着核心作用。然而，只有一小部分感染的女性会患上这种疾病。其他风险因素，包括免疫系统和细胞因子基因中的 SNP，可能是重要的决定因素。
我们研究了细胞因子 TNF-α 启动子 SNP（TNFα-375A、TNFα-307A、TNFα-243A 和 TNFα-237A）在布宜诺斯艾利斯省波萨达斯市（阿根廷）城市女性中发展为高级别宫颈病变和癌症的潜在作用。
将 56 例（CINIII 和浸润性癌）和 113 例年龄匹配的对照纳入研究。通过 PCR 检测 HPV 基因型。通过 PCR 扩增和直接测序基因组 DNA进行 TNFα SNP 基因分型。
我们观察到病例组和对照组之间 TNFα-307A 和 TNFα-375A SNP 的等位基因分布存在差异（p<0.05）。TNFα-307A 变体与宫颈癌相关的 OR 为 2.4（95%CI 1.1-5.4），而 TNFα-375A SNP 在对照组中的出现率为 8.8%，而在病例组中则未出现。此外，TNFα-375A 总是与 TNFα-237A SNP 相关联，表明它们之间存在连锁不平衡。
我们的研究表明，高产生 TNFα-307A 等位基因的存在与波萨达斯人群宫颈癌的发生风险增加相关。我们还推测，TNFα-375A/-237A 单倍型的“保护作用”仅限于对照组，这可能与染色体 6 上的 HLA 基因有关。这些发现有助于我们了解阿根廷人群中免疫基因变异及其在疾病易感性中的作用。
