TLR7 Gln11Leu single nucleotide polymorphism and response to treatment with imiquimod in patients with basal cell carcinoma: a pilot study

Pharmacogenomics. 2015 Nov;16(17):1913-7. doi: 10.2217/pgs.15.132. Epub 2015 Nov 10.

Abstract

Aim: The Toll-like receptor 7 (TLR7) agonist, imiquimod, offers a topical and noninvasive therapeutic method for the clinical treatment of superficial basal cell carcinoma (BCC). In this study we explored the relationship between the functional X-linked TLR7 rs179008/Gln11Leu polymorphism and the response to imiquimod in patients with BCC.

Patients & methods: Thirty-four BCC patients treated with imiquimod were included in the study. SNP genotyping of the TLR7 promoter polymorphism was performed by TaqMan allelic discrimination assay.

Results: In the group of female nonresponders to imiquimod a higher frequency of the altered genotype compared with responders was observed. Similarly, in the group of male nonresponders to imiquimod both patients with the mutated genotype were nonresponders.

Conclusion: The results of this study show that patients carrying at least one T allele of the TLR7 promoter polymorphism are associated with an increased probability to be resistant to imiquimod therapy.

Keywords: Toll-like receptor; basal cell carcinoma; imiquimod; innate immunity; skin.

MeSH terms

  • Aminoquinolines / pharmacology
  • Aminoquinolines / therapeutic use*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Basal Cell / drug therapy
  • Carcinoma, Basal Cell / genetics*
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Glutamine / genetics
  • Humans
  • Imiquimod
  • Leucine / genetics
  • Male
  • Pilot Projects
  • Polymorphism, Single Nucleotide / genetics*
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / genetics*
  • Toll-Like Receptor 7 / agonists
  • Toll-Like Receptor 7 / genetics*
  • Treatment Outcome

Substances

  • Aminoquinolines
  • Antineoplastic Agents
  • TLR7 protein, human
  • Toll-Like Receptor 7
  • Glutamine
  • Leucine
  • Imiquimod