Methylation of a panel of genes in peripheral blood leukocytes is associated with colorectal cancer.

The relationship between the DNA methylation status of the CpG islands of multiple genes in blood leukocytes in CRC susceptibility and prognosis, as well as possible interactions with dietary factors on CRC risk are unclear. We carried out a case-control study including 421 CRC patients and 506 controls to examine the associations between six genes (AOX-1, RARB2, RERG, ADAMTS9, IRF4, and FOXE-1), multiple CpG site methylation (MCSM) and susceptibility to CRC. High-level MCSM (MCSM-H) was defined as methylation of greater than or equal to 2 of 5 candidate genes (except for RARB2); low-level MCSM (MCSM-L) was when 1 candidate gene was methylated; non-MCSM was when none of the candidate genes were methylated. Blood cell-derived DNA methylation status was detected using methylation-sensitive high-resolution melting analysis. The hypermethylation status of each individual gene was statistically significantly associated with CRC. MCSM status was also associated with CRC (OR = 1.54, 95% CI: 1.15–2.05, P = 0.004). We observed interactions between a high level of dietary intake of cereals, pungent food, and stewed fish with brown sauce, age (older than 60 yrs), smoking and hypermethylation on risk of CRC. MCSM in peripheral blood DNA may be an important biomarker for susceptibility to CRC.

结直肠癌（CRC）易感性和预后中血液白细胞多个基因的CpG岛DNA甲基化状态之间的关系，以及与饮食因素在CRC风险方面可能存在的相互作用尚不明确。我们开展了一项病例对照研究，纳入421例CRC患者和506例对照，以检测六个基因（AOX - 1、RARB2、RERG、ADAMTS9、IRF4和FOXE - 1）、多个CpG位点甲基化（MCSM）与CRC易感性之间的关联。高水平MCSM（MCSM - H）定义为5个候选基因（RARB2除外）中≥2个基因甲基化；低水平MCSM（MCSM - L）为1个候选基因甲基化；非MCSM为候选基因均无甲基化。使用甲基化敏感高分辨率熔解分析检测血细胞来源的DNA甲基化状态。每个单独基因的高甲基化状态与CRC具有统计学显著相关性。MCSM状态也与CRC相关（比值比 = 1.54，95%置信区间：1.15 - 2.05，P = 0.004）。我们观察到谷物、辛辣食物和红烧鱼的高膳食摄入量、年龄（>60岁）、吸烟与高甲基化在CRC风险方面存在相互作用。外周血DNA中的MCSM可能是CRC易感性的一个重要生物标志物。