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TNFalpha-308G/A polymorphism as a risk factor for HPV associated cervical cancer in Indian population
Indu Kohaar1, Nisha Thakur, Sudha Salhan
1Division of Molecular Genetics & Biochemistry, Institute of Cytology & Preventive Oncology (ICMR), I-7, Sector 39, Noida, India.
Background:
Investigation of the potential association of single nucleotide polymorphisms (SNPs) at -308 G/A and -238 G/A of Tumor necrosis factor alpha (TNFalpha) with susceptibility to HPV-16 associated cervical cancer in Indian women.
Methods:
The study included 165 histologically confirmed cases with 45 precancer and 120 cancer patients and an equal number (165) of healthy controls with normal cervical cytology. PCR-RFLP was employed to analyze TNFalpha promoter polymorphisms, which were confirmed by direct sequencing. Both patients and controls were screened for Human Papillomavirus (HPV) infection.
Results:
The frequency of -308 A allele in TNFalpha was significantly higher in cases compared with control subjects (21% in cases vs. 9% in controls; p<0.01), with an odds ratio of 2.7 (95% CI = 1.41-5.15). Also, women carrying A allele for this locus presented 3 times increased susceptibility to HPV 16 infection as evident from carrier genotype distribution between HPV positive cases and control subjects (24% in HPV positive cases vs. 9% in controls; p<0.01; OR = 3.1; 95% CI = 1.60-6.03). No such association was found for TNFalpha-238 (G/A) polymorphism with the risk of development of cervical cancer.
Conclusion:
It suggests that SNP at -308 (G/A) of TNFalpha promoter may represent an increased risk for HPV infection and development of cervical cancer in Indian women.
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