Constitutive telomere length and gastric cancer risk: Case-control analysis in Chinese Han population
Constitutive telomere length and gastric cancer risk: Case-control analysis in Chinese Han population
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DOI：
10.1111/j.1349-7006.2009.01169.x
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发表时间：
2009-07-01
期刊：
影响因子：
5.7
通讯作者：
Dong, Guanglong
中科院分区：
文献类型：
--
作者：
Liu, Xiaonan;Bao, Guoqiang;Dong, Guanglong
端粒的缩短可能导致染色体不稳定，从而促进肿瘤的发生。先前的研究已经证明端粒缩短在几种恶性肿瘤的发生中有明确的参与。然而，组成性端粒缩短与胃癌发生之间的关系尚未建立。因此，在本研究中，我们测量平均端粒长度，采用定量实时PCR外周血淋巴细胞胃癌（GC）病例对照研究，包括396例和378例对照。结果显示，胃癌患者的平均端粒长度显著短于匹配的对照组（平均值+/- SD 0.89 +/- 0.19 vs 1.06 +/- 0.25，P < 0.001）。我们进一步将端粒长度分类，使用对照组中的50%值作为分界点，并使用多变量logistic回归分析评估端粒长度与GC风险之间的关联。我们发现短端粒长度与胃癌风险显著增加相关（调整后比值比= 2.14，95%置信区间= 1.52-2.93）。四分位数分层显示端粒缩短和GC风险之间存在剂量反应关系（趋势P < 0.001）。分层分析表明，性别，年龄，饮酒，而不是吸烟和幽门螺杆菌感染，似乎有一个调节作用的平均端粒长度在病例组和对照组。我们还发现端粒缩短和吸烟对GC风险有显著的联合作用。总的来说，我们的研究结果提供了第一个证据，将外周血淋巴细胞端粒长度短与GC风险升高联系起来，这需要在其他人群中进行进一步研究。（Cancer Sci 2009; 100：1300-1305）
The shortening of telomeres may result in chromosome instability and thus promote tumorigenesis. Previous studies have demonstrated clear involvement of telomere shortening in the carcinogenesis of several malignancies. However, the association between constitutive telomere shortening and gastric cancer development has yet to be established. Therefore, in the present study, we measured average telomere length using quantitative real-time PCR in peripheral blood lymphocytes from a gastric cancer (GC) case-control study consisting of 396 cases and 378 controls. The results showed that GC patients had significantly shorter average telomere length than matched controls (mean +/- SD 0.89 +/- 0.19 vs 1.06 +/- 0.25, P < 0.001). We further categorized telomere length using the 50% value in the controls as a cut-off point and assessed the association between telomere length and GC risk using multivariate logistic regression analysis. We found that short telomere length was associated with a significantly increased GC risk (adjusted odds ratio = 2.14, 95% confidence interval = 1.52-2.93). Quartile stratification revealed a dose-response relationship between telomere shortening and GC risk (P for trend < 0.001). Stratified analysis showed that sex, age, and alcohol drinking, but not smoking and Helicobacter pylori infection, seem to have a modulating effect on the average telomere length in both cases and controls. We also found that telomere shortening and smoking had a significant joint effect on GC risk. Collectively, our findings provide the first evidence linking the short telomere length in peripheral blood lymphocytes to elevated GC risk, which warrants further investigation in other populations. (Cancer Sci 2009; 100: 1300-1305)