Telomere length is predictive of breast cancer risk in BRCA2 mutation carriers
Menée à partir de l'analyse, à l'aide d'une technique de PCR quantitative à haut débit, d'échantillons sanguins prélevés sur 561 patientes atteintes d'un cancer du sein sporadique, 169 patientes présentant une mutation du gène BRCA2 et 537 témoins, cette étude met en évidence une association entre la longueur des télomères et le risque de développer un cancer du sein chez les femmes porteuses d'une mutation BRCA2
Background : Germline BRCA2 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 BRCA mutation 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 female BRCA2 mutation 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), both BRCA2 mutation carriers (p=0.0097) and non-carriers (p=0.00006). Using exclusively samples acquired before breast cancer diagnosis, we found that shorter telomeres were significantly associated with increased breast cancer risk in BRCA2 mutation carriers (HR = 3.60, 95% 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 in BRCA2 mutation carriers. Breast cancer cases have significantly shorter TL than unaffected women, regardless of BRCA2 status, 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 Epidemiology Biomarkers & Prevention , résumé, 2016