In:
Cancer Prevention Research, American Association for Cancer Research (AACR), Vol. 1, No. 7_Supplement ( 2008-11-01), p. B40-B40
Abstract:
B40 Bladder cancer is a complex disease involving multiple genes interacting with each other and/or with environment factors in the tumorigenesis process. We examined 245 SNPs of 22 genes of PI3K-AKT-mTOR pathway which is an essential cellular pathway controlling cell growth, proliferation and survival. We used a case-control design with 803 cases and 803 controls systematically evaluate single nucleotide polymorphisms (SNPs) in this pathway as predicators of bladder cancer risk, in close interaction with environmental factors. In individual SNP analysis, increased bladder cancer risk was significantly associated with 20 SNPs (AKT3: rs12045585, RHEB: rs1920978, RPS6KA5: rs8018757, IRS2: rs9515120, TSC2: rs2073636 and rs8063461, and Raptor: rs11653499, rs9890502, rs8071015, rs7211818, rs9915378, rs9674559, rs7208536, rs7219896, rs4969444, rs2672890, rs7212142, rs9897968, rs2271608, and rs1062935) adjusting by age, gender and smoking status using logistic regression. We grouped the unfavorable SNPs into four categories based on the distribution of the control. Compared to the reference group, the second, third and fourth category showed 1.01 (95%CI: 0.76-1.34), 1.16 (95%CI: 0.89-1.50), and significantly 1.53 (95%CI: 1.14-2.07, P=0.005) fold increased risk of bladder cancer respectively (P for the trend: & lt;0.0001). Classification and regression tree (CART) analysis was performed to explore the high order gene-gene and gene-environment interaction. Further stratification, haplotype and diplotype analysis are still ongoing. This is the first study to address the role of germline genetic variation in this pathway as cancer susceptibility factors. The identification of novel genetic susceptibility markers for bladder cancer etiology will not only help understand the biology of bladder carcinogenesis, but also help identify high risk individuals for bladder cancer. These findings warrant further replication in independent populations. Citation Information: Cancer Prev Res 2008;1(7 Suppl):B40.
Type of Medium:
Online Resource
ISSN:
1940-6207
,
1940-6215
DOI:
10.1158/1940-6207.PREV-08-B40
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2008
detail.hit.zdb_id:
2422346-3
