Genetic Variability of the mTOR Pathway and Prostate Cancer Risk in the European Prospective Investigation on Cancer (EPIC)
Author(s)
Type
Journal Article
Abstract
The mTOR (mammalian target of rapamycin) signal transduction pathway integrates various signals, regulating ribosome
biogenesis and protein synthesis as a function of available energy and amino acids, and assuring an appropriate coupling of
cellular proliferation with increases in cell size. In addition, recent evidence has pointed to an interplay between the mTOR
and p53 pathways. We investigated the genetic variability of 67 key genes in the mTOR pathway and in genes of the p53
pathway which interact with mTOR. We tested the association of 1,084 tagging SNPs with prostate cancer risk in a study of
815 prostate cancer cases and 1,266 controls nested within the European Prospective Investigation into Cancer and
Nutrition (EPIC). We chose the SNPs (n = 11) with the strongest association with risk (p,0.01) and sought to replicate their
association in an additional series of 838 prostate cancer cases and 943 controls from EPIC. In the joint analysis of first and
second phase two SNPs of the PRKCI gene showed an association with risk of prostate cancer (ORallele = 0.85, 95% CI 0.78–
0.94, p = 1.361023 for rs546950 and ORallele = 0.84, 95% CI 0.76–0.93, p = 5.661024 for rs4955720). We confirmed this in a
meta-analysis using as replication set the data from the second phase of our study jointly with the first phase of the Cancer
Genetic Markers of Susceptibility (CGEMS) project. In conclusion, we found an association with prostate cancer risk for two
SNPs belonging to PRKCI, a gene which is frequently overexpressed in various neoplasms, including prostate cancer.
biogenesis and protein synthesis as a function of available energy and amino acids, and assuring an appropriate coupling of
cellular proliferation with increases in cell size. In addition, recent evidence has pointed to an interplay between the mTOR
and p53 pathways. We investigated the genetic variability of 67 key genes in the mTOR pathway and in genes of the p53
pathway which interact with mTOR. We tested the association of 1,084 tagging SNPs with prostate cancer risk in a study of
815 prostate cancer cases and 1,266 controls nested within the European Prospective Investigation into Cancer and
Nutrition (EPIC). We chose the SNPs (n = 11) with the strongest association with risk (p,0.01) and sought to replicate their
association in an additional series of 838 prostate cancer cases and 943 controls from EPIC. In the joint analysis of first and
second phase two SNPs of the PRKCI gene showed an association with risk of prostate cancer (ORallele = 0.85, 95% CI 0.78–
0.94, p = 1.361023 for rs546950 and ORallele = 0.84, 95% CI 0.76–0.93, p = 5.661024 for rs4955720). We confirmed this in a
meta-analysis using as replication set the data from the second phase of our study jointly with the first phase of the Cancer
Genetic Markers of Susceptibility (CGEMS) project. In conclusion, we found an association with prostate cancer risk for two
SNPs belonging to PRKCI, a gene which is frequently overexpressed in various neoplasms, including prostate cancer.
Date Issued
2011-02-23
Date Acceptance
2011-01-01
Citation
PLOS One, 2011, 6 (2)
ISSN
1932-6203
Publisher
Public Library of Science
Journal / Book Title
PLOS One
Volume
6
Issue
2
Copyright Statement
© 2011 Campa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
License URL
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
MULTIDISCIPLINARY SCIENCES
KINASE-C-IOTA
KAPPA-B ACTIVATION
TUBEROUS SCLEROSIS
LUNG-CANCER
CELL-GROWTH
PKC-IOTA
MAMMALIAN TARGET
PROTEIN
RAPAMYCIN
COMPLEX
Publication Status
Published
Article Number
e16914