title: A potentially functional polymorphism in the promoter region of miR-34b/c is associated with renal cell cancer risk in a Chinese population.
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.
authors: Department of Urology.
authors: Shaobo
authors: S
authors: Zhang
authors: Jian
authors: J
authors: Qian
authors: Qiang
authors: Q
authors: Cao
authors: Pu
authors: P
authors: Li
authors: Meilin
authors: M
authors: Wang
authors: Jian
authors: J
authors: Wang
authors: Xiaobing
authors: X
authors: Ju
authors: Xiaoxin
authors: X
authors: Meng
authors: Qiang
authors: Q
authors: Lu
authors: Pengfei
authors: P
authors: Shao
authors: Zhengdong
authors: Z
authors: Zhang
authors: Chao
authors: C
authors: Qin
authors: Changjun
authors: C
authors: Yin
mesh_terms: D044466:Asian People / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008156:Luciferases; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D016017:Odds Ratio; D010957:Plasmids / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors
chemical_list: D017931:DNA Primers; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D008156:Luciferases