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Cancer of uterine cervix is the second most common cancer among women worldwide but it is the leading cancer in Indian women. Though high-risk human papillomavirus (HR-HPV) is the major etiological agent for the development of cervical carcinogenesis, HPV infection alone is not sufficient, but together with immunological, environmental or genetic cofactors might be responsible for cervical carcinogenesis. Therefore, we investigated the association of SNPs in TNF-LTA locus with susceptibility to cervical cancer/precancer in 400 subjects comprising 200 cases and 200 controls by PCR-RFLP followed by sequencing and TNF levels by ELISA. Significant association was established for TNFA -308 G/A (Pc =0.01) and LTA +252 A/G (Pc =0.02) polymorphisms with respect to cancer vs. controls. Interestingly, TNFA -857 C/T SNP and AGGCCT haplotype exhibited protective effect for cervical cancer (Pc =0.04), (Pc =0.02). Functional correlation was also established between TNF -308 G/A and elevated plasma levels (P= 0.03). Therefore, SNPs in TNF-LTA locus may play a critical role in cervical carcinogenesis.

Impact of Haplotype TNF-LTA Locus with Susceptibility to Cervical Cancer in Indian Population