RT Journal Article
T1 Mitochondrial DNA copy number variation, leukocyte telomere length, and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.
A1 Campa, Daniele
A1 Barrdahl, Myrto
A1 Santoro, Aurelia
A1 Severi, Gianluca
A1 Baglietto, Laura
A1 Omichessan, Hanane
A1 Tumino, Rosario
A1 Bueno-de-Mesquita, H B As
A1 Peeters, Petra H
A1 Weiderpass, Elisabete
A1 Chirlaque, Maria-Dolores
A1 Rodríguez-Barranco, Miguel
A1 Agudo, Antonio
A1 Gunter, Marc
A1 Dossus, Laure
A1 Krogh, Vittorio
A1 Matullo, Giuseppe
A1 Trichopoulou, Antonia
A1 Travis, Ruth C
A1 Canzian, Federico
A1 Kaaks, Rudolf
K1 Breast cancer
K1 Cancer epidemiology
K1 Mitochondrial copy number
K1 Telomere length
AB Leukocyte telomere length (LTL) and mitochondrial genome (mtDNA) copy number and deletions have been proposed as risk markers for various cancer types, including breast cancer (BC). To gain a more comprehensive picture on how these markers can modulate BC risk, alone or in conjunction, we performed simultaneous measurements of LTL and mtDNA copy number in up to 570 BC cases and 538 controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. As a first step, we measured LTL and mtDNA copy number in 96 individuals for which a blood sample had been collected twice with an interval of 15 years. According to the intraclass correlation (ICC), we found very good stability over the time period for both measurements, with ICCs of 0.63 for LTL and 0.60 for mtDNA copy number. In the analysis of the entire study sample, we observed that longer LTL was strongly associated with increased risk of BC (OR 2.71, 95% CI 1.58-4.65, p = 3.07 × 10- 4 for highest vs. lowest quartile; OR 3.20, 95% CI 1.57-6.55, p = 1.41 × 10- 3 as a continuous variable). We did not find any association between mtDNA copy number and BC risk; however, when considering only the functional copies, we observed an increased risk of developing estrogen receptor-positive BC (OR 2.47, 95% CI 1.05-5.80, p = 0.04 for highest vs. lowest quartile). We observed a very good correlation between the markers over a period of 15 years. We confirm a role of LTL in BC carcinogenesis and suggest an effect of mtDNA copy number on BC risk.
YR 2018
FD 2018-04-17
LK http://hdl.handle.net/10668/12362
UL http://hdl.handle.net/10668/12362
LA en
DS RISalud
RD Apr 19, 2025