G-308A TNF-α polymorphism is associated with an increased risk of invasive cervical cancer

https://doi.org/10.1016/j.bbrc.2005.06.137Get rights and content

Abstract

Cervical cancer is initiated by high-risk human papillomaviruses (HPV-16 and HPV-18), but an effective immune response may control the progression of this disease. Tumor necrosis factor-α (TNF-α) is a pro-inflammatory cytokine, that has been implicated in several cancers. In a case-control study, we evaluated the association between the G-308A TNF-α promoter polymorphism and the risk for invasive cervical cancer (ICC). TNF-α polymorphism was analyzed by PCR-RFLP and confirmed by sequencing. DNA was obtained from blood samples of 439 individuals, including 195 patients with ICC and 244 normal healthy controls. According to our results, women carrying the A allele present a twofold increased risk of developing ICC (p = 0.006; OR = 1.88; 95% CI [1.20–2.94]). In conclusion, our study suggests that the presence of the high producer allele −308A in the TNF-α gene appears to be associated with an increased risk for the development of ICC.

Section snippets

Materials and methods

Subjects. We tested the association between the −308 TNF-α promoter polymorphism and the risk for invasive cervical cancer using a case-control study. We analyzed the DNA obtained from peripheral blood samples of 195 patients admitted in the Portuguese Institute of Oncology, Porto (North Portugal Area) with histologically confirmed invasive squamous cell carcinoma of the uterine cervix. The mean age of the patients at the time of diagnosis was 50 years with a median of 48 (standard deviation

Results

The distribution of TNFA −308 promoter genotypes in healthy controls and in patients with invasive cervical cancer (ICC) is shown in Table 1. We can observe that the rare genotype AA is more frequent in patients than in controls (3.6% in cases and 1.6% in controls). However, the results did not reach statistical significance probably because of the small number of AA carriers present in the population, since the A allele is very rare. When grouping the population that should produce higher

Discussion

Various genetic polymorphisms have been associated with increased risk for cancer [26], [27], the cervical neoplasia being a major health problem in Portugal, since each year it is responsible for approximately 6.3 deaths/100,000 habitants, which is a much higher mortality rate than the European mean [28]. Facing this fact, we conducted a case-control study to analyze the association between the G-308A TNFA polymorphism and the risk to develop invasive cancer of the uterine cervix in the

Acknowledgments

The authors thank Liga Portuguesa Contra o Cancro Porto (Portuguese League Against Cancer) for their support. We gratefully acknowledge funding of this work by the Portuguese Ministry of Health—Comissão Fomento Investigação em Cuidados de Saúde (CFICS-219/1999). We also thank the Projecto Saude XXI—Programa Operacional Ciência, Tecnologia e Inovação (POCTI) do Quadro Comunitário de Apoio II, by Programa Operacional de Saúde/SAUDE XXI (FEDER) and by Associação Portuguesa da Industria

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    Present address: Júlio Dinis Maternity, 4200 Porto, Portugal.

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