Skip Navigation



Carcinogenesis Advance Access published online on October 29, 2009
Carcinogenesis, doi:10.1093/carcin/bgp258
This Article
Right arrow Advance Access manuscript (PDF)
Right arrow Supplementary Data
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Chen, M.
Right arrow Articles by Wu, X.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chen, M.
Right arrow Articles by Wu, X.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Genetic variations in PI3K-AKT-mTOR pathway and bladder cancer risk

Meng Chen1, Adrian Cassidy1, Jian Gu1, George L. Delclos2, Fan Zhen3, Hushan Yang1, Michelle Hildebrandt1, Jie Lin1, Yuanqing Ye1, Robert M. Chamberlain1, Colin P. Dinney4 and Xifeng Wu1

1 Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
2 School of Public Health, Divisions of Environmental and Occupational Health Sciences and Epidemiology, The University of Texas Health Science Center, Houston, Texas
3 Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas
4 Department of Urology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

Correspondence should be addressed to: Xifeng Wu, M.D., Ph.D., Department of Epidemiology, Unit 1340, The University of Texas M. D. Anderson Cancer Center, 1155 Pressler Blvd., Houston, TX77030. Telephone: (713) 745-2485, Fax: (713)792-4657, Email: xwu{at}mdanderson.org

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.

Key Words: mTOR pathway • bladder cancer susceptibility

Received June 3, 2009; revised October 15, 2009; accepted October 17, 2009.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.