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Genetic polymorphisms in cyclin D1 are associated with risk of renal cell cancer in the Chinese population.

ABSTRACT: Recently, the functional polymorphisms in Cyclin D1 (CCND1) have been shown the potential influence to risk of renal cell cancer (RCC). Therefore, the present study was performed to investigate whether these polymorphisms could influence the susceptibility of RCC. Four potentially functional polymorphisms in CCND1 (rs1944129, rs7177, rs9344 and rs678653) were genotyped in this hospital-based case-control study, comprising of 1,488 RCC patients and 1,677 cancer-free controls in a Chinese population by the TaqMan assay. The logistic regression was used to assess the associations between CCND1 polymorphisms and the risk of RCC. We found the genotype and allele frequency distribution of rs1944129 and rs7177 were significantly associated with risk of RCC (P = 0.015 and P = 0.018, respectively). The analysis of combined risk alleles revealed that patients with 2-4 risk alleles showed an elevated risk of RCC compared to those with 0-1 risk alleles (OR = 1.35, 95% CI = 1.15 - 1.58, P < 0.001). Furthermore, compared with the genotypes containing G allele (AG and GG), the patients carrying the AA genotype in CCND1 rs1944129 polymorphism had a significantly greater prevalence of high clinical stage disease (OR = 0.56, 95% CI = 0.33 - 0.94, P = 0.029). These results suggested that these CCND1 polymorphisms rs1944129 and rs7177 might contribute to the susceptibility of RCC in the Chinese population.

SUBMITTER: Xue J

PROVIDER: S-EPMC5655247 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Genetic polymorphisms in cyclin D1 are associated with risk of renal cell cancer in the Chinese population.

Xue Jianxin J Qin Zhiqiang Z Li Xiao X Zhang Jianzhong J Zheng Yuxiao Y Xu Weizhang W Cao Qiang Q Wang Zengjun Z

Oncotarget 20170908 46

Recently, the functional polymorphisms in Cyclin D1 (CCND1) have been shown the potential influence to risk of renal cell cancer (RCC). Therefore, the present study was performed to investigate whether these polymorphisms could influence the susceptibility of RCC. Four potentially functional polymorphisms in CCND1 (rs1944129, rs7177, rs9344 and rs678653) were genotyped in this hospital-based case-control study, comprising of 1,488 RCC patients and 1,677 cancer-free controls in a Chinese populati ...[more]

PMID: 29113352

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Project description:BackgroundThe RhoA/ROCK pathway and Caveolin-1 (Cav-1) participate in the process of tumorigenesis in numerous types of cancer. Up-regulation of RhoA/ROCK and Cav-1 expression is considered to be associated with the development and progression of clear cell renal cell carcinoma (ccRCC). We investigated the association between genetic variations of RhoA/ROCK and Cav-1 and the risk of ccRCC in the Chinese population.MethodsBetween May 2004 and March 2014, a total of 1,248 clear cell renal cell carcinoma cases and 1,440 cancer-free controls were enrolled in this hospital-based case-control study. Nine SNPs in RhoA/ROCK and Cav-1 were genotyped using the TaqMan assay.ResultWe found two SNPs (Cav-1 rs1049334 and ROCK1 rs35996865) were significantly associated with the increasing risk of ccRCC (P = 0.002 and P < 0.001 respectively). The analysis of combined risk alleles revealed that patients with 2-4 risk alleles showed a more remarkable growth of ccRCC risk than the patients with 0-1 risk alleles(OR = 1.66, 95%CI = 1.31-2.11, P < 0.001). Younger subjects (P = 0.001, OR = 1.83, 95%CI = 1.30-2.57), higher weight subjects (P = 0.001, OR = 1.76, 95%CI = 1.25-2.47), female subjects (P = 0.007, OR = 1.75, 95% CI = 1.17-2.62), nonsmokers (P < 0.001, OR = 1.67, 95%CI = 1.26-2.23), drinkers (P = 0.025, OR = 1.75, 95% CI = 1.07-2.85), subjects with hypertension (P = 0.025, OR = 1.75, 95% CI = 1.07-2.85) and diabetes (P = 0.026, OR = 4.31, 95% CI = 1.19-15.62) showed a stronger association between the combined risk alleles and the risk of ccRCC by using the stratification analysis. Furthermore, we observed higher Cav-1 mRNA levels in the presence of the rs1049334 A allele in normal renal tissues.ConclusionOur results indicate that the two SNPs (Cav-1 rs1049334 and ROCK1 rs35996865) and genotypes with a combination of 2-4 risk alleles were associated with the risk of ccRCC. The functional SNP rs1049334 may affect the risk of ccRCC by altering the expression of Cav-1 and the relevance between the risk effects and the functional impact of this polymorphism needs further validation.

Dataset Information

Genetic polymorphisms in cyclin D1 are associated with risk of renal cell cancer in the Chinese population.

Publications

Genetic polymorphisms in cyclin D1 are associated with risk of renal cell cancer in the Chinese population.

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