Interleukin-33 polymorphisms and serum concentrations in mycosis fungoides.

BACKGROUND: Mycosis fungoides (MF) skin lesions are characterized by low-grade inflammation, which may be sustained by proinflammatory cytokines as probably interleukin-33 (IL-33). We compared serum concentrations of IL-33 and its receptor ST2 and the frequency of selected IL-33 single nucleotide polymorphisms (SNPs) between patients with MF and healthy controls. METHODS: In 88 patients with MF and 66 healthy controls, we analyzed SNPs in the 9894 and 11877 loci of the IL-33 gene. Moreover, we measured serum concentrations of IL-33 and its receptor ST2. RESULTS: There were no statistically significant differences in the frequencies of both IL-33 SNPs between patients and controls. Compared with controls, patients with MF had similar IL-33 serum concentrations (P = 0.71) but significantly increased ST2 concentrations (P < 0.001). Patients in MF-IA stage had significantly lower ST2 serum concentrations than those with the remaining MF stages (P = 0.002). The studied variables were not related to pruritus severity. Patients with the C(+) IL-33 11877 SNP had lower ST2 serum concentrations than patients with the C(-) 11877 SNP (P = 0.043). CONCLUSIONS: It was published before that the knockout of the ST2 gene after injection of IL-33 is associated with a reduced inflammatory reaction in the skin, as well as that IL-33 plays a role in allergic and neoplastic disorders. Concerning the difference in ST2 concentration between control and MF group, and C IL-33 11877 SNP possibly influencing the ST2 concentration, the role of IL-33/ST2 signaling, needs further studies.

CA-SSR1 Polymorphism in Intron 1 of the EGFR Gene in Patients with Malignant Tumors Who Develop Acneiform Rash Associated with the Use of Cetuximab.

BACKGROUND AND OBJECTIVE: Epidermal growth factor receptor (EGFR) inhibitors are not equally effective in all cancer patients. One potential clinical factor that could help in selecting patients who may benefit from treatment with cetuximab is acneiform rash, which correlates with the clinical response to EGFR inhibitors. Some previous studies have suggested that the tendency to develop rash may depend on polymorphisms in the EGFR gene. In this investigation, the association of degree of CA dinucleotide polymorphism with skin rash and cetuximab therapy outcome was examined. METHODS: The study included 60 patients treated with cetuximab. For each patient, the severity of acneiform rash was assessed, and the type of polymorphism was determined by genotyping. Associations between genotypes, the acneiform rash, and response to treatment were determined by using the chi-square test and Spearman's rank correlation. The cutoffs S≤17(CA), L>17(CA), n(CA)≤35, and n(CA)>35 were tested, as well as the sum of the two allele repetitions. RESULTS: A correlation was found between body surface area covered by rash and the sum of the two allele repetitions (p=0.030). No statistically significant relationship between genotype and response to treatment was observed. However, in patients who have had partial remission, we noticed a higher incidence of polymorphism, with less CA dinucleotide repetitions and early onset of rash. CONCLUSION: A correlation between genotype and severity of rash was observed. That is, the severity of rash decreased with an increased number of CA repetitions.