Journal Article

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

Meng Chen, Jian Gu, George L. Delclos, Ann M. Killary, Zhen Fan, Michelle A. T. Hildebrandt, Robert M. Chamberlain, H. Barton Grossman, Colin P. Dinney and Xifeng Wu

in Carcinogenesis

Volume 31, issue 8, pages 1387-1391
Published in print August 2010 | ISSN: 0143-3334
Published online June 2010 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgq110
Genetic variations of the PI3K–AKT–mTOR pathway and clinical outcome in muscle invasive and metastatic bladder cancer patients

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

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.

Journal Article.  3310 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.