Department of Community Health Center for Environmental Health, Laboratory Medicine, Brown University, Providence, Rhode Island 02912, USA.
Clin Cancer Res. 2010 Mar 1;16(5):1682-9. doi: 10.1158/1078-0432.CCR-09-2983. Epub 2010 Feb 23.
Epigenetic alterations including changes to cellular DNA methylation levels contribute to carcinogenesis and may serve as powerful biomarkers of the disease. This investigation sought to determine whether hypomethylation at the long interspersed nuclear elements (LINE1), reflective of the level of global DNA methylation, in peripheral blood-derived DNA is associated with increased risk of bladder cancer.
LINE1 methylation was measured from blood-derived DNA obtained from participants of a population-based incident case-control study of bladder cancer in New Hampshire. Bisulfite-modified DNA was pyrosequenced to determine LINE1 methylation status; a total of 285 cases and 465 controls were evaluated for methylation.
Being in the lowest LINE1 methylation decile was associated with a 1.8-fold increased risk of bladder cancer [95% confidence interval (95% CI), 1.12-2.90] in models controlling for gender, age, and smoking, and the association was stronger in women than in men (odds ratio, 2.48; 95% CI, 1.19-5.17 in women; and odds ratio, 1.47; 95% CI, 0.79-2.74 in men). Among controls, women were more likely to have lower LINE1 methylation than men (P = 0.04), and levels of arsenic in the 90th percentile were associated with reduced LINE1 methylation (P = 0.04).
LINE1 hypomethylation may be an important biomarker of bladder cancer risk, especially among women.
包括细胞 DNA 甲基化水平变化在内的表观遗传改变促成了癌症的发生，并可能成为该疾病的强大生物标志物。本研究旨在确定外周血源性 DNA 中的长散在核元件（LINE1）低甲基化是否与膀胱癌风险增加相关，LINE1 低甲基化反映了整体 DNA 甲基化水平。
LINE1 甲基化从新罕布什尔州膀胱癌基于人群的病例对照研究中参与者的血液源性 DNA 中测量。亚硫酸氢盐修饰的 DNA 进行焦磷酸测序以确定 LINE1 甲基化状态；共评估了 285 例病例和 465 例对照的甲基化情况。
在控制性别、年龄和吸烟的模型中，处于 LINE1 最低甲基化十分位数的患者膀胱癌风险增加 1.8 倍[95%置信区间（95%CI），1.12-2.90]，且这种关联在女性中比男性更强（女性的比值比，2.48；95%CI，1.19-5.17；男性的比值比，1.47；95%CI，0.79-2.74）。在对照组中，女性的 LINE1 低甲基化程度比男性更常见（P = 0.04），第 90 百分位数的砷水平与 LINE1 低甲基化相关（P = 0.04）。
LINE1 低甲基化可能是膀胱癌风险的一个重要生物标志物，尤其是在女性中。
