Short Telomere Length and Breast Cancer Risk: A Study in Sister Sets

Abstract Telomeres consist of a tandem repeats of the sequence TTAGGG at the ends of chromosomes and play a key role in the maintenance of chromosomal stability. Previous studies indicated that short telomeres are associated with increased risk for human bladder, head and neck, lung, and renal cell cancer. We investigated the association between white blood cell telomere length and breast cancer risk among 268 family sets (287 breast cancer cases and 350 sister controls). Telomere length was assessed by quantitative PCR. The mean telomere length was shorter in cases (mean, 0.70; range, 0.03–1.95) than in unaffected control sisters (mean, 0.74; range, 0.03–2.29), but no significant difference was observed (P = 0.11). When subjects were categorized according to the median telomere length in controls (0.70), affected sisters had shorter telomeres compared with unaffected sisters after adjusting for age at blood donation and smoking status [odds ratio (OR), 1.3; 95% confidence interval (95% CI), 0.9–1.8], but the association was not statistically significant. The association by quartile of telomere length (Q4 shortest versus Q1 longest) also supported an increase in risk from shorter telomere length, although the association was not statistically significant (OR, 1.6; 95% CI, 0.9–2.7). This association was more pronounced among premenopausal women (OR, 2.1; 95% CI, 0.8–5.5) than postmenopausal women (OR, 1.3; 95% CI, 0.5–3.6 for Q4 versus Q1). If these associations are replicated in larger studies, they provide modest epidemiologic evidence that shortened telomere length may be associated with breast cancer risk. [Cancer Res 2007;67(11):5538–44]