Telomere length shows no association with BRCA1 and BRCA2 mutation status


Session type:

M Tymrakiewicz1, E Killick1, C Cieza-Borrella2, P Smith3, DJ Thompson3, KA Pooley3, E Bancroft4, E Page1, Z Kote-Jarai1, RA Eeles1
1The Institute of Cancer Research, London, UK, 2Universidad de Salamanca, Salamanca, Spain, 3University of Cambridge, Cambridge, UK, 4The Royal Marsden Hospital NHS Trust, London, UK


Telomeres, nucleotide repeats located at the ends of eukaryotic chromosomes, are essential for the maintenance of the genomic integrity. Alterations in telomere length (TL) have been associated with risk of common diseases including cancer in several prospective studies, but no conclusive studies have been undertaken for hereditary cancers caused byBRCA1 andBRCA2 mutations. Our aim was to determine whether TL is a marker of cancer risk or genetic status amongst two cohorts ofBRCA1/2mutation carriers and controls.


We have analysed TL in two distinct cohorts. The first group was a prospective set of 665 male BRCA1/2 mutation carriers and controls and the second group consisted of 283 female BRCA1/2 mutation carriers and controls. TL was quantified by qPCR from DNA extracted from peripheral blood lymphocytes. Weighted and unweighted Cox regressions and linear regression analyses were used to assess whether TL was associated with cancer risk or BRCA1/2 mutation status.


Significant negative correlation between age and TL was observed in both the female and male sets (p= 0.001 and p<0.001 respectively). After correcting for age and plate we found no significant association between cancer status and TL in either of these cohorts. When comparing TL in BRCA1/2 mutation carriers and controls, no association was found between genetic status and TL.


We measured TL in two cohorts of BRCA1/2 mutation carriers and controls, with and without cancer, to investigate the possibility of using TL as a method of risk stratification. A previously published smaller study suggested female BRCA1/2 carriers with breast cancer had shorter TL than their non-mutation carrying unaffected sisters. Our results do not support this finding, nor do they suggest TL would be useful for risk stratification of BRCA1/2 mutation carriers.