Abstract
Members of the miR-34 family have been shown to be transcriptional targets of the tumour suppressor gene P53. Aberration expression of miR-34 impairs p53-mediated cell cycle arrest and apoptosis. A single nucleotide polymorphism T > C (rs4938723) located within the CpG island in the promoter region of pri-miR-34b/c may affect its expression and has been suggested to influence cancer risk. In this study, we genotyped rs4938723 using the TaqMan method to explore the relationship between this polymorphism and the risk of renal cell cancer (RCC) in a case-control study of 710 RCC patients and 760 control subjects. We found that individuals carrying the CC genotype had a significantly increased RCC risk compared with those with TT or TT/TC genotypes [odds ratio (OR) = 1.53, 95% confidence interval (CI) = 1.06-2.21 for CC vs. TT and OR = 1.48, 95% CI = 1.05-2.10 for CC vs. TT/TC). Furthermore, the increased risk was more evident in the subgroups of older subjects (OR = 1.80, 95% CI = 1.08-3.01), males (OR = 1.64, 95% CI = 1.08-2.51), smokers (OR = 2.07, 95% CI = 1.16-3.69) and drinkers (OR = 1.94, 95% CI = 1.01-3.73), although no interaction between rs4938723 and these characteristics was observed. Twenty-seven normal tissues adjacent to tumour were used to evaluate the association between the expression level of miR-34b/c and the polymorphism, which revealed higher expression levels of miR-34b/c in normal renal tissues with TT+TC genotypes than in those with CC genotypes (P < 0.01). Furthermore, a luciferase gene assay in 293-T cells showed that the luciferase activities with rs4938723 T allele are higher than that with C allele (P < 0.05). These results suggest that the miR-34b/c rs4938723 C allele may increase susceptibility to RCC by decreasing the activity of pri-miR-34b/c promoter.
Highlights
Renal cell cancer (RCC) is the most common malignancy of the kidney (>80%) and the 10th most common cause of cancerrelated deaths among men [1,2]
The results suggest that the rs4938723 C allele may decrease the expression of miR-34b/c by altering the promoter activities. To our knowledge, this is the first study to evaluate the association between miR-34b/c rs4938723 polymorphism and RCC risk in a Chinese population
We found that the CC genotype was associated with a statistically significant increased risk of RCC in the Chinese population, and the risk was more evident in subgroups of older subjects, males, smokers and drinkers
Summary
Renal cell cancer (RCC) is the most common malignancy of the kidney (>80%) and the 10th most common cause of cancerrelated deaths among men [1,2]. The promoter regions of the miR-34 family contain CpG islands, and Vogt et al [13] suggested that miR-34 inactivation is a common event in tumour formation, including RCC, and that the CpG methylation of miR-34a and miR-34b/c may have diagnostic value. It is indicated in research by Lodygin et al [14] that the expression of miR-34a is silenced in several cancers including kidney cancers
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