A polymorphism in the interleukin-10 promoter affects the course of disease in patients with clear-cell renal carcinoma.
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.
Romero
José María
JM
Departamento de Bioquímica y Biología Molecular e Inmunología, Universidad de Granada, Spain.
Sáenz-López
Pablo
P
Cózar
José Manuel
JM
Carretero
Rafael
R
Canton
Julia
J
Vazquez
Fernando
F
Concha
Angel
A
Tallada
Miguel
M
Garrido
Federico
F
Ruiz-Cabello
Francisco
F
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
D016753:Interleukin-10