title: A polymorphism in the interleukin-10 promoter affects the course of disease in patients with clear-cell renal carcinoma.
abstract: In the tumor microenvironment, interleukin (IL)-10 production has a pleiotropic ability to positively and negatively influence the function of innate and adaptive immunity against cancer. This study investigated whether IL-10 genetic polymorphisms that influence gene expression levels play a role in the risk and clinical course of clear-cell renal cell carcinoma (RCC). We analyzed the allelic and haplotype frequency formed by alleles at -1082(G/A), -819(C/T), and -592(C/A) of the IL-10 gene in RCC (n = 126) and healthy individuals (n = 176). The frequency of IL-10 polymorphic variants was similar between patients and controls. However, -1082 G/A IL-10 genotype showed a significant association with three prognostic indicators: advanced disease stage (p = 0.002), higher tumor size (p = 0.001), and presence of adenopathy (p = 0.006). Our results can be explained by the contradictory antitumor or pro-tumorigenic relationship between this molecule and cancer. Genotypes associated with high or low levels of IL-10 gene expression (GG or AA-1082 IL-10) were both associated with a more favorable course of the disease. We propose the hypothesis that the -1082 GA medium expression genotype confers a tumor-promoting phenotype, likely resulting from the immunosuppressive effects of anti-tumor Th-1 responses in conjunction with the insufficient inhibition of tumor angiogenesis at this intermediate level of IL-10 expression.
authors.affiliation: Departamento de Bioquímica y Biología Molecular e Inmunología, Universidad de Granada, Spain.
authors.forename: José María
authors.initials: JM
authors.lastname: Romero
authors.forename: Pablo
authors.initials: P
authors.lastname: Sáenz-López
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Cózar
authors.forename: Rafael
authors.initials: R
authors.lastname: Carretero
authors.forename: Julia
authors.initials: J
authors.lastname: Canton
authors.forename: Fernando
authors.initials: F
authors.lastname: Vazquez
authors.forename: Angel
authors.initials: A
authors.lastname: Concha
authors.forename: Miguel
authors.initials: M
authors.lastname: Tallada
authors.forename: Federico
authors.initials: F
authors.lastname: Garrido
authors.forename: Francisco
authors.initials: F
authors.lastname: Ruiz-Cabello
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D055815:Young Adult
chemical_list: D016753:Interleukin-10