TNFalpha polymorphism frequencies in HPV-associated cervical dysplasia

Area of Science:

• Genetics
• Immunology
• Gynecology

Background:

• Persistent high-risk human papillomavirus (HPV) infection is linked to cervical intraepithelial neoplasia (CIN) and cervical cancer.
• Reduced pro-inflammatory responses to HPV may increase susceptibility to viral persistence and cervical neoplasia.

Purpose of the Study:

• To investigate if nucleotide sequence polymorphisms in the Tumor Necrosis Factor-alpha (TNFalpha) gene influence susceptibility to or evolution of CIN.
• To examine the impact of TNFalpha gene polymorphisms on cervical cancer risk.

Main Methods:

• Induced heteroduplex analysis identified TNFalpha polymorphisms at positions -308 and -238 in women with normal cytology and cervical disease.
• Human papillomavirus (HPV) typing and reassessment of disease status at 6 and 24 months were performed for patients with low-grade disease.

Main Results:

• CIN patients exhibited a significantly higher frequency of TNFalpha -308 low-secretor genotypes (GG) compared to controls, particularly in the CIN1 group.
• No significant differences in TNFalpha polymorphism frequencies at position -238 were observed between patients and controls.
• Neither polymorphism was associated with HPV infection status at recruitment or disease outcome at 6 or 24 months.

Conclusions:

• Findings support the hypothesis that TNFalpha -308 polymorphism influences susceptibility to CIN.
• The TNFalpha -308 polymorphism may play a role in the development of cervical intraepithelial neoplasia.