Mitochondrial DNA copy number variation, leukocyte telomere length, and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study
AuthorCampa, D; Barrdahl, M; Santoro, A; Severi, G; Baglietto, L; Omichessan, H; Tumino, R; Bueno-de-Mesquita, HB; Peeters, PH; Weiderpass, E; ...
Source TitleBreast Cancer Research
PublisherBIOMED CENTRAL LTD
AffiliationMelbourne School of Population and Global Health
Document TypeJournal Article
CitationsCampa, D., Barrdahl, M., Santoro, A., Severi, G., Baglietto, L., Omichessan, H., Tumino, R., Bueno-de-Mesquita, H. B., Peeters, P. H., Weiderpass, E., Chirlaque, M. -D., Rodriguez-Barranco, M., Agudo, A., Gunter, M., Dossus, L., Krogh, V., Matullo, G., Trichopoulou, A., Travis, R. C. ,... Kaaks, R. (2018). Mitochondrial DNA copy number variation, leukocyte telomere length, and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. BREAST CANCER RESEARCH, 20 (1), https://doi.org/10.1186/s13058-018-0955-5.
Access StatusOpen Access
BACKGROUND: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
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