Multiple gene-specific DNA methylation in blood leukocytes and colorectal cancer risk: a case-control study in China.

The relationship between gene-specific DNA methylation in peripheral blood leukocytes and colorectal cancer (CRC) susceptibility is unclear. In this case-control study, the methylation status of a panel of 10 CRC-related genes in 428 CRC cases and 428 cancer-free controls were detected with methylation-sensitive high-resolution melting analysis. We calculated a weighted methylation risk score (MRS) that comprehensively combined the methylation status of the panel of 10 genes and found that the MRS_10 was significantly associated with CRC risk. Compared with MRS-Low group, MRS-High group and MRS-Medium group exhibited a 6.51-fold (95% CI, 3.77-11.27) and 3.85-fold (95% CI, 2.72-5.45) increased risk of CRC, respectively. Moreover, the CRC risk increased with increasing MRS_10 (Ptrend < 0.0001). Stratified analyses demonstrated that the significant association retained in both men and women, younger and older, and normal weight or underweight and overweight or obese subjects. The area under the receiver operating characteristic curves for the MRS_10 model was 69.04% (95% CI, 65.57-72.66%) and the combined EF and MRS_10 model yielded an AUC of 79.12% (95% CI, 76.22-82.15%). Together, the panel of 10 gene-specific DNA methylation in leukocytes was strongly associated with the risk of CRC and might be a useful marker of susceptibility for CRC.

外周血白细胞中基因特异性DNA甲基化与大肠癌（CRC）易感性之间的关系尚不清楚。在这项病例对照研究中，通过与甲基化敏感的高分辨率熔融分析一起检测到428例CRC病例中10个与CRC相关基因的甲基化状态。我们计算了一个加权甲基化风险评分（MRS），该评分全面合并了10个基因面板的甲基化状态，发现MRS_10与CRC风险显着相关。与MRS-LOW组相比，MRS-HIGH组和MRS-MEDIUM组分别显示出6.51倍（95％CI，3.77-11.27）和3.85倍（95％CI，2.72-5.45）的CRC风险增加。此外，CRC风险随着MRS_10的增加而增加（Ptrend <0.0001）。分层的分析表明，在年轻人和年龄较大的男性和女性中保留的显着关联以及正常体重，体重不足，超重或肥胖受试者。 MRS_10模型的接收器操作特性曲线下的面积为69.04％（95％CI，65.57-72.66％），EF和MRS_10模型的组合产生的AUC为79.12％（95％CI，76.22-82.15％）。加在一起，白细胞中10个基因特异性DNA甲基化的面板与CRC的风险密切相关，可能是CRC敏感性的有用标记。