A Prospective Study of Relative Telomere Length and Postmenopausal Breast Cancer Risk

Abstract

During breast cancer progression, a substantial increase in chromosomal aberrations is observed in the transition from ductal hyperplasia to carcinoma in situ. Telomeres are essential structures to chromosomal integrity. Consequently, telomere dysfunction, which leads to genomic instability, is hypothesized to play a causal role in the progression of breast cancer. However, the few epidemiologic studies that have assessed the relationship between telomere length and breast cancer risk have been inconsistent. We used quantitative real-time PCR to measure relative telomere length in genomic DNA extracted from peripheral blood leukocytes and examined its association with postmenopausal breast cancer risk in 1,122 invasive breast cancer cases and 1,147 matched controls free of diagnosed cancer nested within the prospective Nurses' Health Study. Our data show that relative telomere length was not associated with a significant elevation in postmenopausal breast cancer risk [below versus above median; odds ratio, 1.23; 95% confidence interval, 0.94-1.60; P(trend) = 0.20]. Estrone and estradiol hormone levels were significantly inversely associated with relative telomere length (P = 0.02). Other established breast cancer risk factors such as family history of breast cancer and history of benign breast disease were not associated with relative telomere length in separate linear regression models each adjusted for age and disease status (P > or = 0.07). Our results provide little support for an important role of telomere length, as measured in peripheral blood leukocytes, as a biomarker of breast cancer risk.