Telomere Length Is Predictive of Breast Cancer Risk in Mutation Carriers.

Cancer Epidemiol Biomarkers Prev 2017 08 24;26(8):1248-1254. Epub 2017 Feb 24.

Cancer Research Laboratory, Biomedical Center, Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

Germline mutations increase risk of breast cancer and other malignancies. BRCA2 has been shown to play a role in telomere protection and maintenance. Telomere length (TL) has been studied as a modifying factor for various diseases, including breast cancer. Previous research on TL in mutation carriers has produced contradicting results. We measured blood TL, using a high-throughput monochrome multiplex qPCR method, in a well-defined Icelandic cohort of female mutation carriers ( = 169), sporadic breast cancer patients ( = 561), and healthy controls ( = 537). Breast cancer cases had significantly shorter TL than unaffected women ( < 0.0001), both mutation carriers ( = 0.0097) and noncarriers ( = 0.00006). Using exclusively samples acquired before breast cancer diagnosis, we found that shorter telomeres were significantly associated with increased breast cancer risk in mutation carriers [HR, 3.60; 95% confidence interval (CI), 1.17-11.28; , 0.025] but not in non-carriers (HR,1.40; 95% CI, 0.89-2.22; , 0.15). We found no association between TL and breast cancer-specific survival. Blood TL is predictive of breast cancer risk in mutation carriers. Breast cancer cases have significantly shorter TL than unaffected women, regardless of status, indicating that samples taken after breast cancer diagnosis should not be included in evaluations of TL and breast cancer risk. Our study is built on a well-defined cohort, highly accurate methods, and long follow-up and can therefore help to clarify some previously published, contradictory results. Our findings also suggest that BRCA2 has an important role in telomere maintenance, even in normal blood cells. .

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http://dx.doi.org/10.1158/1055-9965.EPI-16-0946DOI Listing
August 2017
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