Telomere length variation in normal epithelial cells adjacent to tumor: Potential biomarker for breast cancer local recurrence

Xin Zhou, Alan K. Meeker, Kepher H. Makambi, Ourania Kosti, Bhaskar V.S. Kallakury, Mary K. Sidawy, Christopher A. Loffredo, Yun Ling Zheng

Research output: Contribution to journalArticlepeer-review

Abstract

A better understanding of the risk of local recurrence (LR) will facilitate therapeutic decision making in the management of early breast cancers. In the present study, we investigated whether telomere length in the normal breast epithelial cells surrounding the tumor is predictive of breast cancer LR; 152 women who were diagnosed with breast cancer at the Lombardi Comprehensive Cancer Center were included in this nested case-control study. Cases (patients had LR) and controls (patients had no LR) were matched on year of surgery, age at diagnosis and type of surgery. Telomere fluorescent in situ hybridization was used to determine the telomere length using formalin fixed paraffin-embedded breast tissues. Small telomere length variation (TLV), defined as the coefficient variation of telomere lengths among examined cells, in normal epithelial cells adjacent to the tumor was significantly associated with a 5-fold (95% confidence interval = 1.2-22.2) increased risk of breast cancer LR. When the subjects were categorized into quartiles, a significant inverse dose-response relationship was observed with lowest versus highest quartile odds ratio of 15.3 (P trend = 0.012). Patients who had large TLV had significantly better 10 year recurrence free survival rate compared with patients who had small TLV (80 versus 33%). The present study revealed that TLV in normal epithelial cells adjacent to tumor is a strong predictor of breast cancer LR. If confirmed by future studies, TLV in normal epithelial cells adjacent to tumor has the potential to become a promising biomarker for predicting breast cancer LR after breast conserving surgery.

Original languageEnglish (US)
Pages (from-to)113-118
Number of pages6
JournalCarcinogenesis
Volume33
Issue number1
DOIs
StatePublished - 2012

ASJC Scopus subject areas

  • Cancer Research

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