Telomere Length Is Predictive of Breast Cancer Risk in<i>BRCA2</i>Mutation Carriers

Abstract

<b>Background:</b> Germline <i>BRCA2</i> 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 <i>BRCA</i> mutation carriers has produced contradicting results.<b>Methods:</b> We measured blood TL, using a high-throughput monochrome multiplex qPCR method, in a well-defined Icelandic cohort of female <i>BRCA2</i> mutation carriers (<i>n</i> = 169), sporadic breast cancer patients (<i>n</i> = 561), and healthy controls (<i>n</i> = 537).<b>Results:</b> Breast cancer cases had significantly shorter TL than unaffected women (<i>P</i> < 0.0001), both <i>BRCA2</i> mutation carriers (<i>P</i> = 0.0097) and noncarriers (<i>P</i> = 0.00006). Using exclusively samples acquired before breast cancer diagnosis, we found that shorter telomeres were significantly associated with increased breast cancer risk in <i>BRCA2</i> mutation carriers [HR, 3.60; 95% confidence interval (CI), 1.17-11.28; <i>P</i>, 0.025] but not in non-carriers (HR,1.40; 95% CI, 0.89-2.22; <i>P</i>, 0.15). We found no association between TL and breast cancer-specific survival.<b>Conclusions:</b> Blood TL is predictive of breast cancer risk in <i>BRCA2</i> mutation carriers. Breast cancer cases have significantly shorter TL than unaffected women, regardless of <i>BRCA2</i> status, indicating that samples taken after breast cancer diagnosis should not be included in evaluations of TL and breast cancer risk.<b>Impact:</b> 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. <i>Cancer Epidemiol Biomarkers Prev; 26(8); 1248-54. ©2017 AACR</i>.