Genetic Variants in Caveolin-1 and RhoA/ROCK1 Are Associated with Clear Cell Renal Cell Carcinoma Risk in a Chinese Population

• Published in: PloS one Vol. 10; no. 6; p. e0128771
• Main Authors: Zhao, Ruizhe, Liu, Kang, Huang, Zhengkai, Wang, Jun, Pan, Yongsheng, Huang, Yuan, Deng, Xiaheng, Liu, Jinliang, Qin, Chao, Cheng, Gong, Hua, Lixin, Li, Jie, Yin, Changjun
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.06.2015; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Alleles; Angiogenesis; Asian Continental Ancestry Group; Breast cancer; Cancer; Cancer research; Carcinoma, Renal Cell - epidemiology; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - metabolism; Caveolin; Caveolin 1 - genetics; Caveolin 1 - metabolism; Caveolin-1; China; Clear cell-type renal cell carcinoma; Development and progression; Diabetes; Diabetes mellitus; Female; Gene polymorphism; Genetic diversity; Genetic variance; Genotypes; Hospitals; Humans; Hypertension; Kidney cancer; Kidney Neoplasms - epidemiology; Kidney Neoplasms - genetics; Kidney Neoplasms - metabolism; Kinases; Laboratories; Male; Medical research; Medicine; Metastasis; Middle Aged; Molecular biology; Motility; mRNA; Patients; Polymorphism; Polymorphism, Single Nucleotide; Population; Proteins; Renal cell carcinoma; Reproductive health; Rho-associated kinase; rho-Associated Kinases - genetics; rho-Associated Kinases - metabolism; rhoA GTP-Binding Protein - genetics; rhoA GTP-Binding Protein - metabolism; RhoA protein; Risk analysis; Risk Factors; RNA; Rocks; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Tumorigenesis; Urology; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0128771

The 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. Between 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. We 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. Our 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.