TY - JOUR
T1 - Genetic variability of the mTOR pathway and prostate cancer risk in the european prospective investigation on cancer (EPIC)
AU - Campa, Daniele
AU - Hüsing, Anika
AU - Stein, Angelika
AU - Dostal, Lucie
AU - Boeing, Heiner
AU - Pischon, Tobias
AU - Tjønneland, Anne
AU - Roswall, Nina
AU - Overvad, Kim
AU - Østergaard, Jane Nautrup
AU - Rodríguez, Laudina
AU - Sala, Núria
AU - Sánchez, Maria José
AU - Larrañaga, Nerea
AU - Huerta, José María
AU - Barricarte, Aurelio
AU - Khaw, Kay Tee
AU - Wareham, Nicholas
AU - Travis, Ruth C.
AU - Allen, Naomi E.
AU - Lagiou, Pagona
AU - Trichopoulou, Antonia
AU - Trichopoulos, Dimitrios
AU - Palli, Domenico
AU - Sieri, Sabina
AU - Tumino, Rosario
AU - Sacerdote, Carlotta
AU - van Kranen, Henk
AU - Bueno-de-Mesquita, H. Bas
AU - Hallmans, Göran
AU - Johansson, Mattias
AU - Romieu, Isabelle
AU - Jenab, Mazda
AU - Cox, David G.
AU - Siddiq, Afshan
AU - Riboli, Elio
AU - Canzian, Federico
AU - Kaaks, Rudolf
PY - 2011
Y1 - 2011
N2 - 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 (pallele = 0.85, 95% CI 0.78-0.94, p = 1.3×10-3 for rs546950 and ORallele = 0.84, 95% CI 0.76-0.93, p = 5.6×10-4 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.
AB - 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 (pallele = 0.85, 95% CI 0.78-0.94, p = 1.3×10-3 for rs546950 and ORallele = 0.84, 95% CI 0.76-0.93, p = 5.6×10-4 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.
UR - http://www.scopus.com/inward/record.url?scp=79952021550&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79952021550&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0016914
DO - 10.1371/journal.pone.0016914
M3 - Article
C2 - 21373201
AN - SCOPUS:79952021550
VL - 6
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 2
M1 - e16914
ER -