Background: Erythematous and papulo-pustular eruption (EPPE) is the most common cutaneous adverse reaction induced by Epidermal Growth Factor Receptor inhibitors (EGFRI). This rash greatly worsens the quality of life of patients. Tolllike receptors (TLRs) are a family of receptors involved in immune responses which may present genetic Single Nucleotide Polymorphisms (SNPs) able to alter the gene functionality. A role of some TLRs in the pathogenesis of inflammatory diseases and cancers was recently suggested. It has been reported that TLR9 presents a mutation in its C-1237T SNP which seems to be correlated with several autoimmune diseases, such as atopic dermatitis and asthma. Furthermore, it is possible that some synthetic agonists of TLR9, called CpG-oligodeoxynucleotides, are able to stimulate the antitumoral innate immune response. Objectives: to assess the incidence of TLR9 C-1237T SNP in patients with EPPE induced by EGFRI and the correlations of genotypic variations of TLR9 C-1237T SNP with gender, EPPE and tumor site. Materials and methods: blood sampling for DNA extraction and sequencing to search the TLR9 C-1237T SNP mutation were carried out in 26 patients with EPPE induced by erlotinib in 14, cetuximab in 11, and tovok in 1. The eruption severity was quantified using EGFRISTI (Epidermal Growth Factor Receptor Inhibitor-related Skin Toxicity Index). The rash was considered mild, moderate, or severe if EGFRISTI value was < 20, between 20 and 40, or > 40, respectively. Results: TLR9 C-1237T SNP mutation was found in 30.8% of patients. This percentage is higher than that reported in the literature for Caucasian population (12%). The presence of mutation was correlated with the eruption severity (0% in mild, 26.7% in moderate, 57.1% in severe) and the cancer site (7/15 lung cancers, 1/9 colon/rectum cancers, 0/2 head/neck cancers). Conclusions: the data, if confirmed in a wider number of cases, could allow the screening of patients to be treated with EGFRI because the most serious EPPEs are indicative of better response to cancer treatment
Il valore predittivo del polimorfismo C1237-T di TLR9 mutato nell’eruzione eritemato-papulo-pustolosa da inibitori dei recettori del fattore di crescita epidermico
BELLINI, VERONICA;FIORUCCI, Stefano;RENGA, Barbara;PELLICCIA, Simona;BIANCHI, LEONARDO;LISI, Paolo
2012
Abstract
Background: Erythematous and papulo-pustular eruption (EPPE) is the most common cutaneous adverse reaction induced by Epidermal Growth Factor Receptor inhibitors (EGFRI). This rash greatly worsens the quality of life of patients. Tolllike receptors (TLRs) are a family of receptors involved in immune responses which may present genetic Single Nucleotide Polymorphisms (SNPs) able to alter the gene functionality. A role of some TLRs in the pathogenesis of inflammatory diseases and cancers was recently suggested. It has been reported that TLR9 presents a mutation in its C-1237T SNP which seems to be correlated with several autoimmune diseases, such as atopic dermatitis and asthma. Furthermore, it is possible that some synthetic agonists of TLR9, called CpG-oligodeoxynucleotides, are able to stimulate the antitumoral innate immune response. Objectives: to assess the incidence of TLR9 C-1237T SNP in patients with EPPE induced by EGFRI and the correlations of genotypic variations of TLR9 C-1237T SNP with gender, EPPE and tumor site. Materials and methods: blood sampling for DNA extraction and sequencing to search the TLR9 C-1237T SNP mutation were carried out in 26 patients with EPPE induced by erlotinib in 14, cetuximab in 11, and tovok in 1. The eruption severity was quantified using EGFRISTI (Epidermal Growth Factor Receptor Inhibitor-related Skin Toxicity Index). The rash was considered mild, moderate, or severe if EGFRISTI value was < 20, between 20 and 40, or > 40, respectively. Results: TLR9 C-1237T SNP mutation was found in 30.8% of patients. This percentage is higher than that reported in the literature for Caucasian population (12%). The presence of mutation was correlated with the eruption severity (0% in mild, 26.7% in moderate, 57.1% in severe) and the cancer site (7/15 lung cancers, 1/9 colon/rectum cancers, 0/2 head/neck cancers). Conclusions: the data, if confirmed in a wider number of cases, could allow the screening of patients to be treated with EGFRI because the most serious EPPEs are indicative of better response to cancer treatmentI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
