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]

The role of telomere biology in bone marrow failure and other disorders

“…Three independent studies of bladder cancer found that individuals with bladder cancer had shorter telomeres in either blood or buccal cells than healthy control subjects (Broberg et al 2005;McGrath et al 2007;Wu et al 2003). Similar findings were noted in patients with head, neck, lung, and breast cancers (Shen et al 2007;Wu et al 2003). In these studies, telomere length differences between cases and controls were statistically significant, but the profound telomere shortening seen in DC was not present in germline DNA from these cases.…”

IFNL cytokines do not modulate human or murine NK cell functions

“…In addition, it has been suggested that measuring telomere length may help predict risk of occurrence of certain types of cancer [22][23][24] including BRCA mutationassociated breast cancer [25,26]. There is some evidence to suggest that exercise may affect telomere length.…”

Telomere length and LINE1 methylation is associated with chromosomal aberrations in peripheral blood

“…Telomeres are of great importance in maintaining chromosomal stability and cellular DNA damage and repair (Hahn, 2003;Callen and Surralles, 2004;Blasco, 2005;Rodier et al, 2005). Short average telomere length in peripheral blood appears to be a susceptibility marker for human breast, bladder, head and neck, lung, and renal cell cancers (Wu et al, 2003;Broberg et al, 2005;Shen et al, 2007;Jang et al, 2008) and meta studies show that the presence of shortened telomeres is a marker for susceptibility to human cancer, but for which cancer types is not clearly established Wentzensen et al, 2011). Short telomere length caused chromosomal instability and epithelial carcinogenesis in mice (Artandi et al, 2000).…”