Genetic variants in RKIP are associated with clear cell renal cell carcinoma risk in a Chinese population.
BACKGROUND: 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). Herein,...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4199597?pdf=render |
| _version_ | 1811238010550747136 |
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| author | Qiang Cao Jian Wang Mingcong Zhang Pu Li Jian Qian Shaobo Zhang Lei Zhang Xiaobing Ju Meilin Wang Zhengdong Zhang Jie Li Min Gu Wei Zhang Chao Qin Pengfei Shao Changjun Yin |
| author_facet | Qiang Cao Jian Wang Mingcong Zhang Pu Li Jian Qian Shaobo Zhang Lei Zhang Xiaobing Ju Meilin Wang Zhengdong Zhang Jie Li Min Gu Wei Zhang Chao Qin Pengfei Shao Changjun Yin |
| author_sort | Qiang Cao |
| collection | DOAJ |
| description | BACKGROUND: 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). Herein, we hypothesized that genetic polymorphisms in RKIP might be associated with susceptibility and progression of RCC. METHODS: A 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. RESULT: We 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. CONCLUSION: Our 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. |
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| id | doaj.art-9b3638d86e0b4829acb1f1e5cc8c2029 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T12:34:24Z |
| publishDate | 2014-01-01 |
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| series | PLoS ONE |
| spelling | doaj.art-9b3638d86e0b4829acb1f1e5cc8c20292022-12-22T03:32:56ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01910e10928510.1371/journal.pone.0109285Genetic variants in RKIP are associated with clear cell renal cell carcinoma risk in a Chinese population.Qiang CaoJian WangMingcong ZhangPu LiJian QianShaobo ZhangLei ZhangXiaobing JuMeilin WangZhengdong ZhangJie LiMin GuWei ZhangChao QinPengfei ShaoChangjun YinBACKGROUND: 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). Herein, we hypothesized that genetic polymorphisms in RKIP might be associated with susceptibility and progression of RCC. METHODS: A 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. RESULT: We 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. CONCLUSION: Our 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.http://europepmc.org/articles/PMC4199597?pdf=render |
| spellingShingle | Qiang Cao Jian Wang Mingcong Zhang Pu Li Jian Qian Shaobo Zhang Lei Zhang Xiaobing Ju Meilin Wang Zhengdong Zhang Jie Li Min Gu Wei Zhang Chao Qin Pengfei Shao Changjun Yin Genetic variants in RKIP are associated with clear cell renal cell carcinoma risk in a Chinese population. PLoS ONE |
| title | Genetic variants in RKIP are associated with clear cell renal cell carcinoma risk in a Chinese population. |
| title_full | Genetic variants in RKIP are associated with clear cell renal cell carcinoma risk in a Chinese population. |
| title_fullStr | Genetic variants in RKIP are associated with clear cell renal cell carcinoma risk in a Chinese population. |
| title_full_unstemmed | Genetic variants in RKIP are associated with clear cell renal cell carcinoma risk in a Chinese population. |
| title_short | Genetic variants in RKIP are associated with clear cell renal cell carcinoma risk in a Chinese population. |
| title_sort | genetic variants in rkip are associated with clear cell renal cell carcinoma risk in a chinese population |
| url | http://europepmc.org/articles/PMC4199597?pdf=render |
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