Abstract
BackgroundTelomere length in peripheral blood leukocytes (PBL-TL) was proposed as a biomarker of cancer risk. Recent scientific evidence suggested PBL-TL plays a diverse role in different cancers. Inconsistent results were obtained on PBL-TL in relation to breast cancer risk and specifically to the presence of BRCA1 and BRCA2 mutations. The aim of the present case-control study was to analyse the correlation between family history of breast cancer or presence of a BRCA mutation and PBL-TL in the hypothesis that TL is a modifier of cancer risk.MethodsPBL-TL was measured using the real-time quantitative PCR method in DNA for 142 cases and 239 controls. All the women enrolled were characterized for cancer family history. A subgroup of 48 women were classified for the presence of a BRCA mutation. PBL-TL were summarized as means and standard deviations, and compared by standard analysis of variance. A multivariable Generalised Linear Model was fitted to the data with PBL-TL as the dependent variable, case/control status and presence of a BRCA/VUS mutation as factors, and age in 4 strata as a covariate.ResultsAge was significantly associated with decreasing PBL-TL in controls (p = 0.01), but not in BC cases. The telomere length is shorter in cases than in controls after adjusting for age. No effect on PBL-TL of BMI, smoke nor of the most common risk factors for breast cancer was observed. No association between PBL-TL and family history was detected both in BC cases and controls. In the multivariate model, no association was observed between BRCA mutation and decreased PBL-TL. A statistically significant interaction (p = 0.031) between case-control status and a BRCA-mutation/VUS was observed, but no effect was detected for the interaction of cancer status and BRCA or VUS.ConclusionOur study fails to provide support to the hypothesis that PBL-TL is associated with the risk of hereditary BC, or that is a marker of inherited mutations in BRCA genes.
Highlights
Genomic instability and in particular its most common form chromosomal instability is thought to be an early event and driving force in tumorigenesis [1,2]
Age was significantly associated with decreasing peripheral blood leucocytes (PBL)-Telomere length (TL) in controls (p = 0.01), but not in Breast cancer (BC) cases
No association between PBL-TL and family history was detected both in BC cases and controls
Summary
Genomic instability and in particular its most common form chromosomal instability (i.e. structural or numerical chromosome aberrations) is thought to be an early event and driving force in tumorigenesis [1,2]. An essential mechanism for chromosome integrity is represented by the coverage of their end provided by telomeres. In their absence, with each cell division genetic materials would be lost [4]. TL in proliferating tissues progressively shortens with each division of somatic cells and TL in peripheral blood leucocytes (PBL) is considered a marker of biological age [12]. Recent scientific evidence suggested PBL-TL plays a diverse role in different cancers. Inconsistent results were obtained on PBL-TL in relation to breast cancer risk and to the presence of BRCA1 and BRCA2 mutations. The aim of the present casecontrol study was to analyse the correlation between family history of breast cancer or presence of a BRCA mutation and PBL-TL in the hypothesis that TL is a modifier of cancer risk
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