Polymorphisms in the IL-13 and IL-4R genes are associated with the development of renal cell carcinoma.
BACKGROUND
Cytokines are the important modulators that bind to their relevant receptors in response to some stimuli to mediate the homeostasis. It has been suggested that the imbalance of immune system of the host might affect the generation of diseases, including cancers.


METHODS
We investigated the association between six functional polymorphisms of IL-4, IL-13, and IL-4R genes and susceptibility to renal cell cancer in a hospital-based study, including 620 renal cell carcinoma (RCC) patients and 623 controls. Logistic regression model was used to assess the genetic effects on the development of RCC.


RESULTS
Overall, individuals with IL-4R Ile50Val CT/TT genotypes had a 0.34-fold significantly decreased RCC risk (CT/TT versus CC), and the T variant allele was associated with a decreased risk of RCC in a dose-response manner (Ptrend=0.009). In addition, we also observed that IL-13 C-1055T and Arg130Gln polymorphisms could decrease the risk of RCC [TT versus
odds ratio=0.36, 95% confidence interval (CI)=0.16-0.78; AA versus GG/GA: 0.66, 0.44-0.97, respectively]. Furthermore, a multiplicative interaction association between the combined IL-4R Ile50Val and IL-13 C-1055T genotypes was observed to decrease the risk of RCC (P=0.036).


CONCLUSIONS
IL-13 and IL-4R may play an important role in the etiology of RCC.
State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing; Department of Molecular & Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing.
H
H
Chu
Department of Molecular & Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing; Department of Occupational Medicine and Environmental Health, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing.
M
M
Wang
Department of Molecular & Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing; Department of Occupational Medicine and Environmental Health, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing.
F
F
Yan
State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing; Department of Occupational Medicine and Environmental Health, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing.
D
D
Zhong
Department of Molecular & Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing; Department of Occupational Medicine and Environmental Health, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing.
D
D
Shi
Department of Molecular & Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing; Department of Occupational Medicine and Environmental Health, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing.
L
L
Ma
Department of Core Laboratory, the Third Affiliated Hospital of Nanjing Medical University, Yizheng.
X
X
Pan
Department of Urology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
C
C
Qin
Department of Urology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
C
C
Yin
State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing; Department of Molecular & Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing; Department of Occupational Medicine and Environmental Health, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing. Electronic address: drzdzhang@gmail.com.
Z
Z
Zhang
D002292:Carcinoma, Renal Cell / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics*; D053662:Interleukin-4 Receptor alpha Subunit / Q000235:genetics*; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
C504000:IL4R protein, human; D018793:Interleukin-13; D053662:Interleukin-4 Receptor alpha Subunit