Deciphering the impact of genetic variation of the TLR9 gene in cervical cancer pathogenesis

Abstract

Cervical carcinogenesis is a multi-step process associated with refractory infection by high-risk human papillomavirus (HPV) types. Only a minority of HPV infected women develop cervical intraepithelial neoplasia (CIN) or cervical cancer, indicating that HPV infection is not the sole risk factor to induce cervical cancer. The present study aimed to identify the association of toll like receptor 9 (TLR9) (2848C>T; rs352140) single neucleotide polymorphism (SNP) with cervical cancer in East Indian women. Study subjects comprised 71 women with histologically proven cervical cancer, and 100 women with benign cervical lesions. The case group included HPV 16 +ve subjects with malignancy. Among subjects with benign lesions, 43 were HPV 16 +ve (intermediate group) and 57 were HPV –ve (control group). TLR9 genotyping was performed using PCR RFLP. TLR9 expression was analyzed using real time PCR. For the C2848T polymorphism of TLR9, the TT genotype and the T allele frequency were significantly increased in the case group compared to those in the control group and the intermediate group. Our study suggests that the TLR9 C2848T polymorphism may be a genetic risk factor for cervical cancer and the progression from HPV infection to cervical cancer.