Lemnrau, A., Brook, M. N., Fletcher, O., Coulson, P., Tomczyk, K., Jones, M., Ashworth, A., Swerdlow, A., Orr, N., Garcia-Closas, M. (2015) Mitochondrial DNA Copy Number in Peripheral Blood Cells and Risk of Developing Breast Cancer. CANCER RESEARCH, 75 (14). pp. 2844-2850. ISSN 0008-5472

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Abstract

Increased mitochondrial DNA (mtDNA) copy number in peripheral blood cells (PBC) has been associated with the risk of developing several tumor types. Here we evaluate sources of variation of this biomarker and its association with breast cancer risk in a prospective cohort study. mtDNA copy number was measured using quantitative real-time PCR on PBC DNA samples from participants in the UK-based Breakthrough Generations Study. Temporal and assay variation was evaluated in a serial study of 91 women, with two blood samples collected approximately 6-years apart. Then, associations with breast cancer risk factors and risk were evaluated in 1,108 cases and 1,099 controls using a nested case-control design. In the serial study, mtDNA copy number showed low assay variation but large temporal variation [assay intraclass correlation coefficient (ICC), 79.3%-87.9%; temporal ICC, 38.3%). Higher mtDNA copy number was significantly associated with younger age at blood collection, being premenopausal, having an older age at menopause, and never taking HRT, both in cases and controls. Based on measurements in a single blood sample taken on average 6 years before diagnosis, higher mtDNA copy number was associated with increased breast cancer risk [OR (95% CI) for highest versus lowest quartile, 1.37 (1.02-1.83); Ptrend = 0.007]. In conclusion, mtDNA copy number is associated with breast cancer risk and represents a promising biomarker for risk assessment. The relatively large temporal variation should be taken into account in future analyses. (C)2015 AACR.

Item Type:	Article
Authors (ICR Faculty only):	Swerdlow, Anthony and Orr, Nicholas and Garcia-Closas, Montse and Jones, Michael and Fletcher, Olivia and Ashworth, Alan
All Authors:	Lemnrau, A., Brook, M. N., Fletcher, O., Coulson, P., Tomczyk, K., Jones, M., Ashworth, A., Swerdlow, A., Orr, N., Garcia-Closas, M.
Additional Information:	ISI Document Delivery No.: CO7EK Times Cited: 0 Cited Reference Count: 21 Lemnrau, Alina Brook, Mark N. Fletcher, Olivia Coulson, Penny Tomczyk, Katarzyna Jones, Michael Ashworth, Alan Swerdlow, Anthony Orr, Nick Garcia-Closas, Montserrat Breakthrough Breast Cancer; Institute of Cancer Research; NHS The authors thank the study participants for the time, effort, and commitment they have given, and the doctors, nurses, and other healthcare staff who have taken blood samples and sent information, and their colleagues in the BGS Team. This work was supported by Breakthrough Breast Cancer and The Institute of Cancer Research. The authors acknowledge NHS funding to the NIHR Institute of Cancer Research/Royal Marsden Hospital Biomedical Research Centre. Amer assoc cancer research Philadelphia
Uncontrolled Keywords:	oxidative stress association cohort
Research teams:	ICR divisions > Breast Cancer Research > Aetiological Epidemiology ICR divisions > Genetics and Epidemiology > Aetiological Epidemiology ICR divisions > Breast Cancer Research > Gene Function ICR divisions > Molecular Pathology > Gene Function ICR divisions > Breast Cancer Research > Complex Trait Genetics Closed research groups > Molecular Epidemiology
Depositing User:	Alexander Smithson
Date Deposited:	01 Sep 2015 12:40
Last Modified:	09 Dec 2015 13:40
URI:	http://publications.icr.ac.uk/id/eprint/14340

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