Shen Jing, Terry Mary Beth, Gurvich Irina, Liao Yuyan, Senie Ruby T, Santella Regina M
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York 10032, USA.
Cancer Res. 2007 Jun 1;67(11):5538-44. doi: 10.1158/0008-5472.CAN-06-3490.
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.
端粒由染色体末端的TTAGGG序列串联重复组成，在维持染色体稳定性方面发挥关键作用。先前的研究表明，短端粒与人类膀胱癌、头颈癌、肺癌和肾细胞癌风险增加相关。我们在268个家庭组（287例乳腺癌病例和350名姐妹对照）中调查了白细胞端粒长度与乳腺癌风险之间的关联。通过定量PCR评估端粒长度。病例组的平均端粒长度（平均值为0.70；范围为0.03 - 1.95）短于未受影响的对照姐妹（平均值为0.74；范围为0.03 - 2.29），但未观察到显著差异（P = 0.11）。当根据对照中的端粒长度中位数（0.70）对受试者进行分类时，在调整献血年龄和吸烟状况后，受影响的姐妹与未受影响的姐妹相比端粒更短[比值比（OR）为1.3；95%置信区间（95%CI）为0.9 - 1.8]，但该关联无统计学意义。按端粒长度四分位数（Q4最短与Q1最长）划分的关联也支持端粒长度越短风险增加，尽管该关联无统计学意义（OR为1.6；95%CI为0.9 - 2.7）。这种关联在绝经前女性中（OR为2.1；95%CI为0.8 - 5.5）比绝经后女性中（Q4与Q1相比，OR为1.3；95%CI为0.5 - 3.6）更明显。如果这些关联在更大规模的研究中得到重复验证，它们将提供适度的流行病学证据，表明端粒长度缩短可能与乳腺癌风险相关。
