Abstract
BackgroundRaf-1 kinase inhibitor protein (RKIP) plays a critical role in tumor development by regulating cell functions such as invasion, apoptosis and differentiation. Down-regulation of RKIP expression has been implicated in the development and progression of renal cell carcinoma (RCC). Herein, we hypothesized that genetic polymorphisms in RKIP might be associated with susceptibility and progression of RCC.MethodsA total of 5 tagging single-nucleotide polymorphisms (tSNPs) in RKIP were selected and genotyped by SNapShot method in a case-control study of 859 RCC patients and 1004 controls. The logistic regression was used to evaluate the genetic association with occurrence and progression of RCC. The functionality of the important SNP was preliminary examined by qRT-PCR.ResultWe found that the rs17512051 in the promoter region of RKIP was significantly associated with decreased clear cell RCC (ccRCC) risk (TA/AA vs. TT: P = 0.039, OR = 0.78, 95%CI = 0.62–0.99). Another SNP (rs1051470) in the 3′UTR region of RKIP was marginally associated with increased ccRCC risk (TT vs. CC+CT: OR = 1.45, 95%CI = 1.01–2.09). In the stratified analysis, the protective effect of rs17512051 was more predominant in the subgroups of male, non-smokers, non-drinkers as well as subjects without history of diabetes. Furthermore, we observed higher RKIP mRNA levels in the presence of the rs17512051A allele in normal renal tissues.ConclusionOur results suggest that the potentially functional RKIP rs17512051 polymorphism may affect ccRCC susceptibility through altering the endogenous RKIP expression level. Risk effects and the functional impact of this polymorphism need further validation.
Highlights
Kidney cancer is the 13th most common cancer globally
We classified the disease according to World Health Organization (WHO) criteria and staged it according to the American Joint Committee on Cancer (AJCC) TNM classification
We found that the rs17512051 in the 59UTR region of Raf-1 kinase inhibitor protein (RKIP) was significantly associated with Clear cell renal cell carcinoma (ccRCC) risk
Summary
About 270,000 cases are diagnosed as kidney cancer while 116,000 die from this disease [1]. Clear cell renal cell carcinoma (ccRCC) is a major pathologic form, which accounts for about 90% of kidney malignancies. Some people will not develop RCC they are exposed to these risk factors during their lifetime. Accumulation of studies indicated that both environmental and genetic factors played critical roles in the tumorigenesis of RCC [4]. Raf-1 kinase inhibitor protein (RKIP) plays a critical role in tumor development by regulating cell functions such as invasion, apoptosis and differentiation. Down-regulation of RKIP expression has been implicated in the development and progression of renal cell carcinoma (RCC). We hypothesized that genetic polymorphisms in RKIP might be associated with susceptibility and progression of RCC
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