| Title | Genetic variations in PI3K-AKT-mTOR pathway and bladder cancer risk. | | Author(s) | Chen M, Cassidy A, Gu J, Delclos GL, Zhen F, Yang H, Hildebrandt M, Lin J, Ye Y, Chamberlain RM, Dinney CP, Wu X | | Institution | Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas. | | Source | Carcinogenesis 2009 Oct 29. | | Abstract | Genetic variations in PI3K-AKT-mTOR pathway may affect critical cellular functions and increase an individual's cancer risk. We systematically evaluate 231 single nucleotide polymorphisms (SNPs) in 19 genes in the PI3K-AKT-mTOR signaling pathway as predictors of bladder cancer risk. In individual SNP analysis, 4 SNPs in RAPTOR remained significant after correcting for multiple testing: rs11653499 (OR: 1.79, 95%CI: 1.24-2.60, P = 0.002), rs7211818 (OR: 2.13, 95%CI: 1.35-3.36, P = 0.001), rs7212142 (OR: 1.57, 95%CI: 1.19-2.07, P = 0.002), and rs9674559 (OR: 2.05, 95%CI: 1.31-3.21, P = 0.002), among which rs7211818 and rs9674559 are within the same haplotype block. In haplotype analysis, compared to the most common haplotypes, haplotype containing the rs7212142 wild type allele showed a protective effect of bladder cancer (OR:0.83, 95%CI: 0.70-0.97). In contrast, the haplotype containing the rs7211818 variant allele showed a 1.32-fold elevated bladder cancer risk (95%CI: 1.09-1.60). In combined analysis of 3 independent significant RAPTOR SNPs (rs11653499, rs7211818, and rs7212142), a significant trend was observed for increased risk with an increase in the number of unfavorable genotypes (P for trend<0.001). Compared to the subjects without any of the unfavorable genotypes, those carrying all 3 unfavorable genotypes showed a 2.22 fold (95%CI: 1.33-3.71) fold increased bladder cancer risk. This is the first study to evaluate the role of germline genetic variations in PI3K-AKT-mTOR pathway as cancer susceptibility factors which will help us identify high risk individuals for bladder cancer. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19875696 |
|
