title: Impact of chemotherapy on telomere length in sporadic and familial breast cancer patients.
abstract: 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.
authors.affiliation: Human Genetics Group, Spanish National Cancer Research Center (CNIO), 28029, Madrid, Spain, cbenitez@cnio.es.
authors.forename: C
authors.initials: C
authors.lastname: Benitez-Buelga
authors.forename: L
authors.initials: L
authors.lastname: Sanchez-Barroso
authors.forename: M
authors.initials: M
authors.lastname: Gallardo
authors.forename: María
authors.initials: M
authors.lastname: Apellániz-Ruiz
authors.forename: L
authors.initials: L
authors.lastname: Inglada-Pérez
authors.forename: K
authors.initials: K
authors.lastname: Yanowski
authors.forename: J
authors.initials: J
authors.lastname: Carrillo
authors.forename: L
authors.initials: L
authors.lastname: Garcia-Estevez
authors.forename: I
authors.initials: I
authors.lastname: Calvo
authors.forename: R
authors.initials: R
authors.lastname: Perona
authors.forename: M
authors.initials: M
authors.lastname: Urioste
authors.forename: A
authors.initials: A
authors.lastname: Osorio
authors.forename: M A
authors.initials: MA
authors.lastname: Blasco
authors.forename: C
authors.initials: C
authors.lastname: Rodriguez-Antona
authors.forename: J
authors.initials: J
authors.lastname: Benitez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D009154:Mutation; D012307:Risk Factors; D016615:Telomere / Q000235:genetics* / Q000378:metabolism; D059506:Telomere Shortening; D055815:Young Adult