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Carcinogenesis. 2010 Aug;31(8):1387-91. doi: 10.1093/carcin/bgq110. Epub 2010 Jun 7.

Genetic variations of the PI3K-AKT-mTOR pathway and clinical outcome in muscle invasive and metastatic bladder cancer patients.

Author information

1
Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, 77030, USA.

Abstract

The phosphoinositide-3 kinase (PI3K)-AKT- mammalian target of rapamycin (mTOR) pathway is an important cellular pathway controlling cell growth, tumorigenesis, cell invasion and drug response. We hypothesized that genetic variations in the PI3K-AKT-mTOR pathway may affect the survival in muscle invasive and metastatic bladder cancer (MiM-BC) patients. We conducted a follow-up study of 319 MiM-BC patients to systematically evaluate 289 single-nucleotide polymorphisms (SNPs) of 20 genes in the PI3K-AKT-mTOR pathway as predicators of survival. In multivariate Cox regression, AKT2 rs3730050, PIK3R1 rs10515074 and RAPTOR rs9906827 were significantly associated with survival. In combined analysis, we found a cumulative effect of these three SNPs on survival. With the increasing number of unfavorable genotypes, there was a significant trend of higher risk of death in multivariate Cox regression (P for trend <0.001) and shorter median survival time in Kaplan-Meier estimates (P log rank <0.001). This is the first study to evaluate the role of germ line genetic variations in the PI3K-AKT-mTOR pathway genes as predictors of MiM-BC clinical outcomes. These findings warrant further replication in independent populations and may provide information on disease management and development of target therapies.

PMID:
20530239
PMCID:
PMC2915631
DOI:
10.1093/carcin/bgq110
[Indexed for MEDLINE]
Free PMC Article

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