BRCA1/2 mutation carriers who have been treated with PS have a substantially reduced breast cancer incidence and mortality. Clin Cancer Res; 22(15); 3971-81. ©2016 AACR.

Our findings suggest that miR-152 can act as a tumor suppressor that targets TGFα. miR-152 is a promising molecular target that inhibits PCa cell migration and invasion.

BackgroundThe mTOR signaling pathway plays a crucial role in the carcinogenesis of renal cell cancer (RCC). We sought to investigate the influence of genetic variations in the mTOR pathway-related genes on the risk of RCC.MethodsWe genotyped 8 potentially functional polymorphisms in AKT1, AKT2, PTEN and MTOR genes using the TaqMan method in a case-control study of 710 RCC patients and 760 cancer-free subjects. Unconditional logistic regression, adjusted for potential confounding factors, was used to assess the risk associations. We then examined the functionality of the important polymorphisms.ResultsOf the 8 polymorphisms, after adjusting for multiple comparisons, we found a significant association between one variant (rs2295080) in the promoter of MTOR and reduced RCC risk (P = 0.005, OR = 0.74, 95%CI = 0.59–0.91, TG/GG vs. TT). Another variant (rs701848) in the 3′UTR region of PTEN was associated with increased RCC risk (P = 0.014, OR = 1.45, 95%CI = 1.08–1.96, CC vs. TT); however, the association was not significant after adjusting for multiple comparisons. Furthermore, we observed lower MTOR mRNA levels in the presence of the rs2295080G allele in normal renal tissues. The luciferase reporter assay showed that the rs2295080G allele significantly decreased luciferase activity. No other significant association between the selected polymorphisms and RCC risk was observed.ConclusionsOur results suggest that the functional MTOR promoter rs2295080 variant affects RCC susceptibility by modulating the endogenous MTOR expression level. The risk effects and the functional impact of the MTOR rs2295080 variant need further validation.