[Polymorphisms in inflammatory response genes in metastatic renal cancer].
Inflammation has been implicated as an etiological factor in different human cancers. Allelic variations in the genes implicated in inflammation are candidates as genetic determinants or markers of renal carcinoma risk. The present stud investigates whether polymorphisms of the genes that give rise to increases in the levels of proinflammatory cytokines and chemokines are associated with an increased risk of renal carcinoma. To this effect, a number of case-control studies were designed to assess the correlation between renal carcinoma and polymorphisms IL10-1082 A/G (rs 1800896), IL10-592 A/C (rs 1800872), IL10-819 C/T (rs 1800871), IL10-1082 A/G, IL4-590 C/T (rs 2243250), TNF-A-308 A/G (rs 1800629), RANTES-403 G/A (rs 2107538), IL1-A-889 C/T (rs 1800587), MCP-1 2518 G/A (rs 1024611), CTLA-4/+49 A/G (rs 231775) and CTLA-4 CT60 A/G (rs 3087243) in 127 renal carcinoma patients and in 176 healthy subjects. The results obtained in relation to cytokine polymorphism IL-10-1082 A/G indicate that AG heterozygosity status is the principal risk factor in relation to locally advanced or metastatic tumor stage and renal carcinoma. In the case of the molecule CTLA4, the results obtained in renal cancer reveal an association between the polymorphisms of the CTLA-4 gene and an increased risk of developing renal cell carcinoma. A high genotypic frequency of polymorphisms CTLA4/CT60-AA and CTLA4/A49G-AA is observed in patients with renal cell carcinoma versus the controls. An association has been established between polymorphism CTLA4/CT60 and tumor grade in patients with renal cell carcinoma. Logistic regression analysis has confirmed these data, demonstrating a high frequency of the AA genotype in patients with high-grade tumors. The results obtained support the hypothesis that different genetic factors implicated in the regulation of adaptive immune responses, stromal cell composition and local cytokine production levels may be crucial elements in the modification of the clinicopathological parameters of renal carcinoma.
Sáenz López
Pablo
P
Servicio de Análisis Clínicos e Inmunología, Hospital Universitario Virgen de las Nieves, Granada, España.
Vázquez Alonso
Fernando
F
Romero
José M
JM
Carretero
Rafael
R
Tallada Buñuel
Miguel
M
Ruiz Cabello
Francisco
F
Cózar Olmo
José Manuel
JM
D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000276:immunology* / Q000556:secondary; D016022:Case-Control Studies; D018925:Chemokines / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D007680:Kidney Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D009362:Neoplasm Metastasis / Q000235:genetics; D011110:Polymorphism, Genetic
D018925:Chemokines; D016207:Cytokines; D016753:Interleukin-10