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

Objective: 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. Methods: 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. Results: 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. Conclusions: This prospective investigation does not support telomere length in blood cells as a biomarker for breast cancer risk.