Genetic Polymorphisms of the Interleukin-4 Receptor α Gene Are Associated with an Increasing Risk and a Poor Prognosis of Sporadic Renal Cell Carcinoma in a Japanese Population

Purpose: It has been suggested that the immune system of the host may be capable of modulating the clinical course of renal cell carcinoma (RCC) patients. In fact, the amount of Th2 cytokines such as interleukin (IL)-4 and IL-10 in the serum of patients has been found to be an important predictor of poor prognosis. Recently, it was reported that genetic polymorphisms of the IL-4 receptor α ( IL-4R α) gene affect the strength of signaling through the receptor. In addition, these same polymorphisms were found to be associated with an increased risk of atopy by causing Th2-dominated responses of the host. The significance of the polymorphisms on the incidence and prognosis in sporadic RCC patients were examined to clarify the role of IL-4 as well as that of the Th1/Th2 immune system in this disease. Experimental Design: A case-control study was performed with 143 sporadic RCCs in a Japanese population and 205 Japanese controls. Logistic regression models were also used to assess the genetic effects on prognosis. Results: The frequencies of variant alleles that enhance signaling of IL-4 were significantly related to an increased risk of RCC. Furthermore, multivariate regression analysis showed that the genotype of the IL-4R gene was an independent prognostic factor for cause-specific survival ( P = 0.018) together with M classification ( P = 0.0002) and histopathological grade ( P = 0.044). Conclusions: The present findings show that the preferential Th2-type response to tumors was associated with a poorer prognosis and suggest that polymorphisms of the IL-4R α gene may serve as useful genetic markers for assessing the risk of the development and progression of RCC.