Benitez-Buelga C, Sanchez-Barroso L, Gallardo M, Apellániz-Ruiz María, Inglada-Pérez L, Yanowski K, Carrillo J, Garcia-Estevez L, Calvo I, Perona R, Urioste M, Osorio A, Blasco M A, Rodriguez-Antona C, Benitez J
Human Genetics Group, Spanish National Cancer Research Center (CNIO), 28029, Madrid, Spain,
Breast Cancer Res Treat. 2015 Jan;149(2):385-94. doi: 10.1007/s10549-014-3246-6. Epub 2014 Dec 21.
Recently, we observed that telomeres of BRCA1/2 mutation carriers were shorter than those of controls or sporadic breast cancer patients, suggesting that mutations in these genes might be responsible for this event. Given the contradictory results reported in the literature, we tested whether other parameters, such as chemotherapy, could be modifying telomere length (TL). We performed a cross-sectional study measuring leukocyte TL of 266 sporadic breasts cancer patients treated with first-line chemotherapy, with a median follow-up of 240 days. Additionally, we performed both cross-sectional and longitudinal studies in a series of 236 familial breast cancer patients that included affected and non-affected BRCA1/2 mutation carriers. We have measured in leukocytes from peripheral blood: the TL, percentage of short telomeres (<3 kb), telomerase activity levels and the annual telomere shortening speed. In sporadic cases we found that chemotherapy exerts a transient telomere shortening effect (around 2 years) that varies depending on the drug combination. In familial cases, only patients receiving treatment were associated with telomere shortening but they recovered normal TL after a period of 2 years. Chemotherapy affects TL and should be considered in the studies that correlate TL with disease susceptibility.
最近，我们观察到BRCA1/2突变携带者的端粒比对照组或散发性乳腺癌患者的端粒短，这表明这些基因的突变可能是导致这一现象的原因。鉴于文献报道的结果相互矛盾，我们测试了其他参数，如化疗，是否会改变端粒长度（TL）。我们进行了一项横断面研究，测量了266例接受一线化疗的散发性乳腺癌患者的白细胞TL，中位随访时间为240天。此外，我们对236例家族性乳腺癌患者进行了横断面和纵向研究，其中包括受影响和未受影响的BRCA1/2突变携带者。我们测量了外周血白细胞中的TL、短端粒（<3 kb）百分比、端粒酶活性水平和每年的端粒缩短速度。在散发性病例中，我们发现化疗会产生短暂的端粒缩短效应（约2年），这取决于药物组合。在家族性病例中，只有接受治疗的患者与端粒缩短有关，但在2年后他们的TL恢复正常。化疗会影响TL，在将TL与疾病易感性相关联的研究中应予以考虑。
