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: 2.74). 07/2011; 22(7):1061-6. DOI: 10.1007/s10552-011-9778-8
Source: PubMed


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.

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    • "Age and lifestyle factors like obesity and smoking are known to be important determinants of telomere length. In our data, however, there were no significant associations of obesity or smoking with relative telomere length [23]. Age was significantly associated with telomere length, but there was no evidence of effect modification of the association between telomere length and individual SNPs by age groups (age <55 years vs. ≥55 years). "
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    ABSTRACT: Telomere length, a biomarker of aging and age-related diseases, exhibits wide variation between individuals. Common genetic variation may explain some of the individual differences in telomere length. To date, however, only a few genetic variants have been identified in the previous genome-wide association studies. As emerging data suggest epigenetic regulation of telomere length, we investigated 72 single nucleotide polymorphisms (SNPs) in 46 genes that involve DNA and histone methylation as well as telomerase and telomere-binding proteins and DNA damage response. Genotyping and quantification of telomere length were performed in blood samples from 989 non-Hispanic white participants of the Sister Study, a prospective cohort of women aged 35-74 years. The association of each SNP with logarithmically-transformed relative telomere length was estimated using multivariate linear regression. Six SNPs were associated with relative telomere length in blood cells with p-values<0.05 (uncorrected for multiple comparisons). The minor alleles of BHMT rs3733890 G>A (p = 0.041), MTRR rs2966952 C>T (p = 0.002) and EHMT2 rs558702 G>A (p = 0.008) were associated with shorter telomeres, while minor alleles of ATM rs1801516 G>A (p = 0.031), MTR rs1805087 A>G (p = 0.038) and PRMT8 rs12299470 G>A (p = 0.019) were associated with longer telomeres. Five of these SNPs are located in genes coding for proteins involved in DNA and histone methylation. Our results are consistent with recent findings that chromatin structure is epigenetically regulated and may influence the genomic integrity of telomeric region and telomere length maintenance. Larger studies with greater coverage of the genes implicated in DNA methylation and histone modifications are warranted to replicate these findings.
    PLoS ONE 07/2012; 7(7):e40504. DOI:10.1371/journal.pone.0040504 · 3.23 Impact Factor
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    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 · 3.23 Impact Factor
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    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
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