Russo Irene, Cona Camilla, Saponeri Andrea, Bassetto Franco, Baldo Vincenzo, Alaibac Mauro
Dermatology Unit, Department of Medicine, University of Padova, I-35121 Padova, Italy.
Plastic Surgery Unit, University of Padova, I-35128 Padova, Italy.
Biomed Rep. 2016 Apr;4(4):459-462. doi: 10.3892/br.2016.597. Epub 2016 Feb 15.
Non-melanoma skin cancers (NMSC) are the most common form of human skin cancer. The majority of NMSC are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) with a BCC:SCC incidence ratio of 4:1 in immunocompetent patients. Toll-like receptors (TLRs) are transmembrane glycoproteins that recognize pathogen-associated molecular patterns and damage-associated molecular patterns, against which they activate the innate immune response and initiate the adaptive immune response. Genetic variations of these receptors can alter the immune system and are involved in evolution and susceptibility of various diseases, including cancer. Imiquimod, an agonist of TLR7, is applied topically in the treatment of premalignant and malignant skin disorders, in particular BCC. The high efficacy of this TLR7 agonist toward BCC supports a possible role of this receptor in the induction of BCC and, consequently, polymorphisms of this receptor could be responsible for a greater or lesser susceptibility to BCC. The aim of the present study was to evaluate whether the presence of the functional TLR7 rs179008/Gln11Leu promoter polymorphism conferred an increased susceptibility to BCC. A case-control study with 177 BCC cases and 158 controls was performed to highlight the possible association between this polymorphism and the susceptibility to BCC. As the TLR7 gene is localized on chromosome X, the allelic frequency of this polymorphism was analyzed separately in males and females. The analysis of the distribution of frequencies of wild-type TLR7 and variant TLR7 carrying the single-nucleotide polymorphism (SNP) rs179008 in patients with BCC and healthy subjects did not reveal any statistically significant difference between cases and controls. This study does not suggest the involvement of the SNP rs179008 of TLR7 in the susceptibility to BCC, but cannot exclude a role for TLR7 in BCC carcinogenesis considering the high efficacy of the TLR7 agonist, imiquimod, in the treatment of this neoplastic disorder.
非黑色素瘤皮肤癌（NMSC）是人类皮肤癌最常见的形式。大多数NMSC为基底细胞癌（BCC）和鳞状细胞癌（SCC），在免疫功能正常的患者中，BCC与SCC的发病率之比为4:1。Toll样受体（TLR）是跨膜糖蛋白，可识别病原体相关分子模式和损伤相关分子模式，并据此激活先天免疫反应并启动适应性免疫反应。这些受体的基因变异可改变免疫系统，并参与包括癌症在内的各种疾病的发生发展和易感性。咪喹莫特是TLR7的激动剂，局部应用于治疗癌前和恶性皮肤疾病，尤其是BCC。这种TLR7激动剂对BCC的高效性支持了该受体在BCC诱导中可能发挥的作用，因此，该受体的多态性可能导致对BCC的易感性有高有低。本研究的目的是评估功能性TLR7 rs179008/Gln11Leu启动子多态性的存在是否会增加患BCC的易感性。进行了一项病例对照研究，纳入177例BCC患者和158名对照，以突出这种多态性与BCC易感性之间的可能关联。由于TLR7基因位于X染色体上，因此分别分析了男性和女性中该多态性的等位基因频率。对BCC患者和健康受试者中携带单核苷酸多态性（SNP）rs179008的野生型TLR7和变异型TLR7的频率分布分析未发现病例组和对照组之间有任何统计学上的显著差异。本研究并不表明TLR7的SNP rs179008与BCC易感性有关，但考虑到TLR7激动剂咪喹莫特在治疗这种肿瘤性疾病方面的高效性，不能排除TLR7在BCC致癌过程中的作用。
