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Title: Genetic Variability of the mTOR Pathway and Prostate Cancer Risk in the European Prospective Investigation on Cancer (EPIC)
Author: Campa, Daniele
Hüsing, Anika
Stein, Angelika
Dostal, Lucie
Boeing, Heiner
Pischon, Tobias
Tjønneland, Anne
Roswall, Nina
Overvad, Kim
Østergaard, Jane Nautrup
Rodríguez, Laudina
Sala Serra, Núria
Sánchez, María José
Larrañaga, Nerea
Huerta Castaño, José María
Barricarte, Aurelio
Khaw, Kay-Tee
Wareham, Nicholas J.
Travis, Ruth C.
Allen, Naomi E.
Lagiou, Pagona
Trichopoulou, Antonia
Trichopoulos, Dimitrios
Palli, Domenico
Sieri, Sabina
Tumino, Rosario
Sacerdote, Carlotta
van Kranen, Henk
Bueno de Mesquita, H. Bas
Hallmans, Göran
Johansson, Mattias
Romieu, Isabelle
Jenab, Mazda
Cox, David G.
Siddiq, Afshan
Riboli, Elio
Canzian, Federico
Kaaks, Rudolf
Keywords: Càncer de pròstata
Polimorfisme genètic
Prostate cancer
Genetic polymorphisms
Issue Date: 23-Feb-2011
Publisher: Public Library of Science (PLoS)
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 (OR(allele) = 0.85, 95% CI 0.78-0.94, p = 1.3 x 10(-3) for rs546950 and OR(allele) = 0.84, 95% CI 0.76-0.93, p = 5.6 x 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.
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It is part of: PLoS One, 2011, vol. 6, num. 2, p. e16914
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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