Telomere length in peripheral blood and breast cancer risk in a prospective case-cohort analysis: results from the Sister Study

Epidemiology Branch, National Institute of Environmental Health Sciences, PO Box 12233, MD A3-05, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, USA.
Cancer Causes and Control (Impact Factor: 2.96). 07/2011; 22(7):1061-6. DOI: 10.1007/s10552-011-9778-8
Source: PubMed

ABSTRACT Telomeres are required for maintaining genomic integrity and may play a role in carcinogenesis. Some, but not all, epidemiologic studies have found that short telomeres in leukocytes are associated with an increased risk of breast cancer. To further elucidate this potential association, we examined telomere length in relation to breast cancer risk in prospectively collected blood samples from the Sister Study, a cohort of women aged 35-74 years who have a sister with breast cancer.
We performed a case-cohort analysis comparing incident breast cancer cases (n = 342) with a subcohort (n = 735), randomly selected from 29,026 participants, enrolled by June 1, 2007. Relative telomere length in peripheral blood cells was estimated using a single-tube monochrome multiplex quantitative PCR assay.
No association was observed between telomere length and breast cancer risk. Compared with the longest quartile, hazard ratios (HR) associated with the second, third, and the shortest quartile were 0.91 [95% confidence interval (95% CI): 0.62-1.34], 1.11 (95% CI: 0.77-1.60), and 0.93 (95% CI: 0.64-1.35), respectively. Subgroup analyses by menopausal status, invasiveness, or estrogen receptor status of breast cancer did not reveal evidence of association between telomere length in blood cells and subsequent breast cancer risk.
This prospective investigation does not support telomere length in blood cells as a biomarker for breast cancer risk.

Download full-text


Available from: Christine G Parks, Aug 10, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Studies examining the association between telomere length and cancer risk have often relied on measurement of telomere length from a single blood draw using a real-time PCR technique. We examined the reliability of telomere length measurement using sequential samples collected over a 9-month period. Relative telomere length in peripheral blood was estimated using a single tube monochrome multiplex quantitative PCR assay in blood DNA samples from 27 non-pregnant adult women (aged 35 to 74 years) collected in 7 visits over a 9-month period. A linear mixed model was used to estimate the components of variance for telomere length measurements attributed to variation among women and variation between time points within women. Mean telomere length measurement at any single visit was not significantly different from the average of 7 visits. Plates had a significant systematic influence on telomere length measurements, although measurements between different plates were highly correlated. After controlling for plate effects, 64% of the remaining variance was estimated to be accounted for by variance due to subject. Variance explained by time of visit within a subject was minor, contributing 5% of the remaining variance. Our data demonstrate good short-term reliability of telomere length measurement using blood from a single draw. However, the existence of technical variability, particularly plate effects, reinforces the need for technical replicates and balancing of case and control samples across plates.
    PLoS ONE 09/2011; 6(9):e25774. DOI:10.1371/journal.pone.0025774 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Telomeres play a critical role in chromosome stability. Telomere length (TL) shortening is a risk factor for cancers. Measuring TL in surrogate tissues that can be easily collected may provide a potential tool for early detection of cancers. A number of studies on surrogate tissue TL and cancer risks have been conducted and results are inconsistent, including positive, negative, or null associations. In this article, we reviewed the published data on surrogate tissue TL in relation to cancer risks, discussed the possible reasons for the differences in the results and future directions and challenges for this line of research.
    Cancer letters 01/2012; 319(2):130-5. DOI:10.1016/j.canlet.2012.01.028 · 5.62 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Telomeres play a key role in the maintenance of chromosome integrity and stability, and telomere shortening is involved in initiation and progression of malignancies. The aim of this study was to determine whether telomere length is associated with the colorectal carcinoma. A total of 148 colorectal cancer (CRC) samples and corresponding adjacent non-cancerous tissues were evaluated for telomere length, P53 mutation, and cyclooxygenase-2 (COX-2) mutation detected by fluorescent immunohistochemistry. Telomere length was estimated by real-time PCR. Samples with a T/S>1.0 have an average telomere length greater than that of the standard DNA; samples with a T/S<1.0 have an average telomere length shorter than that of the standard DNA. Telomeres were shorter in CRCs than in adjacent tissues, regardless of tumor stage and grade, site, or genetic alterations (P=0.004). Telomere length in CRCs also had differences with COX-2 status (P=0.004), but did not differ with P53 status (P=0.101), tumor progression (P=0.244), gender (P=0.542), and metastasis (0.488). There was no clear trend between T/S optimal cut-off values (<1 or > 1) and colorectal tumor progression, metastasis, gender, P53 and COX-2 status. These findings suggesting that telomere shortening is associated with colorectal carcinogenesis but does not differ with tumor progression, gender, and metastasis.
    Asian Pacific journal of cancer prevention: APJCP 02/2012; 13(2):443-6. DOI:10.7314/APJCP.2012.13.2.443 · 2.51 Impact Factor
Show more