Analysis of IL10 gene promoter haplotypes and changes in mRNA expression and soluble levels in patients with basal cell carcinoma

Interleukin-10 (IL-10) is an immunomodulatory molecule that may play an immunosuppressive role in nonmelanoma skin cancer (NMSC), specifically basal cell carcinoma (BCC). We analyzed the role of IL10 promoter variants in genetic determinants of BCC susceptibility and their association with IL10 mRNA and IL-10 serum levels. Three promoter variants (- 1082 A > G, - 819 T > C, and - 592 A > C) were examined in 250 BCC patients and 250 reference group (RG) individuals. IL10 relative gene expression was evaluated in total leucocytes in peripheral blood, and IL-10 levels were quantified in serum. The allelic and genotypic frequencies did not show significant differences between the groups. However, haplotype analysis revealed that the ATA haplotype was associated with a decreased risk of BCC (OR: 0.73, 95% CI 0.56-0.95, p = 0.02), whereas the ATC and ACA haplotypes were associated with an increased risk for the neoplasia (OR: 4.15, 95% CI 1.56-11.04, p < 0.01, and OR: 3.51, 95% CI 1.33-9.29, p < 0.01, respectively). BCC patients showed a 0.09-fold reduction in IL10 mRNA expression compared to the RG. Significant differences were in IL-10 median serum levels between the RG and BCC patients (0.4 vs 0.64 pg/mL, p = 0.02). Significant median serum differences were also observed between low- and high-grade histopathological BCC (0.34 vs 1.35 pg/mL, p = 0.02). The ATA, ATC, and ACA haplotypes, and serum IL-10 levels, could be markers of susceptibility to BCC in Western Mexican individuals. BCC patients had higher serum IL-10 levels than the RG, with levels increasing with the severity of lesions, confirming the role of IL-10 in immunosuppression in neoplasia.