Impact of Toll-like receptors [TLR] 2 (−196 to −174 del) and TLR 4 (Asp299Gly, Thr399Ile) in cervical cancer susceptibility in North Indian women

Abstract: Objective(s): Targeting the Toll-like receptor (TLR) signaling pathway in elucidating the cellular and molecular mechanisms of human diseases, including cervical cancer, is gaining tremendous importance. The aim of our study was to identify the role of TLR 2(−196 to −174 del) and TLR 4(Asp299Gly and Thr399Ile) gene polymorphisms in cervical cancer susceptibility in North Indian women. Methods: For the study, blood samples were collected from histopathologically confirmed patients of cervical cancer (n =150) and unrelated, healthy female controls of similar ethnicity (n =150). Genomic DNA was extracted from peripheral blood leukocytes using salting-out method. TLR 2 and TLR 4 genotyping was done using Polymerase Chain Reaction and Restriction Fragment Length Polymorphism followed by 10% polyacrylamide gel electrophoresis. Results: TLR 2 del allele showed significant association (p =0.048, OR=1.6 [95%CI=1.00–2.51]) with cervical cancer susceptibility, while no significant association was found with TLR 4 (Asp299Gly and Thr399Ile). However, TLR 4 Thr/Ile genotype was found to be significantly associated with early stage (Stage II) of cervical cancer (p =0.044, OR=2.51 [95%CI=1.03–6.12]). Furthermore, TLR 2 ins/del genotype showed strong association (p =0.015, OR=1.95 [95%CI=1.14–3.33]) with tobacco usage in women with cervical cancer. Conclusion(s): Our study highlighted the involvement of TLR 2 (−196 to −174 del) and TLR 4 (Thr399Ile) gene polymorphisms in cervical cancer susceptibility. The TLR gene polymorphisms, upon further evaluation, may be helpful in elucidation of immunobiological mechanisms associated with cervical cancer susceptibility. [Copyright &y& Elsevier]