Objectives: Persistent high-risk HPV infection of the uterine cervix is associated with CIN and cervical carcinoma. Women with a reduced pro-inflammatory response to HPV are likely to be susceptible to viral persistence, and therefore, potentially more vulnerable to cervical neoplasia. In this study, we investigate whether nucleotide sequence polymorphisms in the TNFalpha (TNFSF2) gene (which can modify gene transcription up to 9-fold) might influence susceptibility to, or evolution of, CIN.
Methods: Induced heteroduplex analysis was used to identify polymorphisms at positions TNFalpha -308 and -238 in women with normal cervical cytology and with cervical disease. Patients with low-grade disease were HPV typed using general primer GP5+/6+ PCR/EIA and reverse line blotting, and were reassessed for disease status at 6 and 24 months.
Results: CIN patients as a group had a significantly higher frequency of TNFalpha -308 low-secretor genotypes (GG) compared to controls, and this effect was most pronounced in the CIN1 group (P = 0.01 and P = 0.004, respectively). TNFalpha polymorphism frequencies at position -238 were similar for patients and controls. Neither polymorphism was associated with the presence of HPV infection at recruitment or disease outcome at 6 or 24 months.
Conclusions: These findings support the hypothesis that susceptibility to CIN is influenced by TNFalpha -308 polymorphism.