Abstract
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.
Highlights
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 clear cell renal cell carcinoma (ccRCC)
Renal cell carcinoma accounts for the majority, which is more than 80%, of the malignancy of renal and the clear cell type is the most common subtype
The tagging SNPs (tSNP) of rs1049337 in Cav-1 was excluded from further analysis because of the allele frequencies in control group not conforming to Hardy–Weinberg equilibrium (HWE) (P
Summary
Renal cell carcinoma accounts for the majority, which is more than 80%, of the malignancy of renal and the clear cell type is the most common subtype. It is reported that clear cell renal cell carcinoma(ccRCC) has become the seventh most common cancer type for its steady increase annually, accounting for 270,000 newly diagnosed cases and estimated 116,000 cancer deaths [1]. It is reported that western people show higher morbidity compared with Chinese population, which may be a result of geographic, lifestyle and genetic variations. Studies associated with the risk factors of ccRCC demonstrated that smoking, drinking, HBP and high BMI might contribute to the tumorgenesis. Only a small number of people who share the same risk factors suffer from this disease, indicating that genetic variation may be an assignable reason of the origin of tumor
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