Genetic variability of the mTOR pathway and prostate cancer risk in the european prospective investigation on cancer (EPIC)

Daniele Campa, Anika Hüsing, Angelika Stein, Lucie Dostal, Heiner Boeing, Tobias Pischon, Anne Tjønneland, Nina Roswall, Kim Overvad, Jane Nautrup Østergaard, Laudina Rodríguez, Núria Sala, Maria José Sánchez, Nerea Larrañaga, José María Huerta, Aurelio Barricarte, Kay Tee Khaw, Nicholas Wareham, Ruth C. Travis, Naomi E. AllenPagona Lagiou, Antonia Trichopoulou, Dimitrios Trichopoulos, Domenico Palli, Sabina Sieri, Rosario Tumino, Carlotta Sacerdote, Henk van Kranen, H. Bas Bueno-de-Mesquita, Göran Hallmans, Mattias Johansson, Isabelle Romieu, Mazda Jenab, David G. Cox, Afshan Siddiq, Elio Riboli, Federico Canzian, Rudolf Kaaks

Research output: Contribution to journalArticlepeer-review

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 (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.

Original languageEnglish
Article numbere16914
JournalPLoS One
Volume6
Issue number2
DOIs
Publication statusPublished - 2011

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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