Analysis of TNFα promoter SNPs and the risk of cervical cancer in urban populations of Posadas (Misiones, Argentina)

Abstract

BACKGROUND: 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. OBJECTIVE: We investigated the potential role of cytokine TNF-a promoter SNPs (TNFa-375A, TNFa-307A, TNFa-243A, and TNFa-237A) in the development of high-grade cervical lesions and cancer in urban women from Posadas (Misiones, Argentina). STUDY DESIGN: 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. RESULTS: We observed differences in the allelic distribution of TNFa-307A and TNFa-375A SNPs among cases and controls (p 0.05). The TNFa-307A variant was associated with cervical cancer at an OR 2.4 (CI 95% 1.1-5.4), while the TNFa-375A SNP was identified in 8.8% of the controls and none of the cases. Moreover, the TNFa-375A always occurred in association with the TNFa-237A SNP,indicating linkage disequilibrium between them. CONCLUSION: Our study suggests that the presence of the high producer allele TNFa-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 TNFa-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.

Background: 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. Objective: We investigated the potential role of cytokine TNF- promoter SNPs (TNF-375A, TNF-307A, TNF-243A, and TNF-237A) in the development of high-grade cervical lesions and cancer in urban women from Posadas (Misiones, Argentina). Study design: Fifty-six cases (CINIII and invasive carcinoma) and 113 age-matched controls were included in the study. HPV genotype detection was conducted by PCR. TNF SNP genotyping was conducted through PCR amplification and direct sequencing of genomic DNA. Results: We observed differences in the allelic distribution of TNF-307A and TNF-375A SNPs among cases and controls (p < 0.05). The TNF-307A variant was associated with cervical cancer at an OR 2.4 (CI 95% 1.1–5.4), while the TNF-375A SNP was identified in 8.8% of the controls and none of the cases. Moreover, the TNF-375A always occurred in association with the TNF-237A SNP, indicating linkage disequilibrium between them. Conclusion: Our study suggests thatthe presence ofthe high producer allele TNF-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 TNF-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.