title: Telomere Length Is Predictive of Breast Cancer Risk inBRCA2Mutation Carriers.
abstract: Background:GermlineBRCA2mutations 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 inBRCAmutation carriers has produced contradicting results.Methods:We measured blood TL, using a high-throughput monochrome multiplex qPCR method, in a well-defined Icelandic cohort of femaleBRCA2mutation carriers (n= 169), sporadic breast cancer patients (n= 561), and healthy controls (n= 537).Results:Breast cancer cases had significantly shorter TL than unaffected women (P< 0.0001), bothBRCA2mutation carriers (P= 0.0097) and noncarriers (P= 0.00006). Using exclusively samples acquired before breast cancer diagnosis, we found that shorter telomeres were significantly associated with increased breast cancer risk inBRCA2mutation carriers [HR, 3.60; 95% confidence interval (CI), 1.17-11.28;P, 0.025] but not in non-carriers (HR,1.40; 95% CI, 0.89-2.22;P, 0.15). We found no association between TL and breast cancer-specific survival.Conclusions:Blood TL is predictive of breast cancer risk inBRCA2mutation carriers. Breast cancer cases have significantly shorter TL than unaffected women, regardless ofBRCA2status, indicating that samples taken after breast cancer diagnosis should not be included in evaluations of TL and breast cancer risk.Impact: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.Cancer Epidemiol Biomarkers Prev; 26(8); 1248-54. ©2017 AACR.
authors.affiliation: Cancer Research Laboratory, Biomedical Center, Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
authors.forename: Birna
authors.initials: B
authors.lastname: Thorvaldsdottir
authors.affiliation: Cancer Research Laboratory, Biomedical Center, Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
authors.forename: Margret
authors.initials: M
authors.lastname: Aradottir
authors.affiliation: Cancer Research Laboratory, Biomedical Center, Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
authors.forename: Olafur A
authors.initials: OA
authors.lastname: Stefansson
authors.affiliation: Cancer Research Laboratory, Biomedical Center, Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
authors.forename: Sigridur K
authors.initials: SK
authors.lastname: Bodvarsdottir
authors.affiliation: Cancer Research Laboratory, Biomedical Center, Faculty of Medicine, University of Iceland, Reykjavik, Iceland. jorunne@hi.is.
authors.forename: Jorunn E
authors.initials: JE
authors.lastname: Eyfjörd
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D024522:Genes, BRCA2 / Q000502:physiology*; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D016615:Telomere / Q000473:pathology*