Methylation Status of Transcriptional Modulatory Genes Associated with Colorectal Cancer in Northeast China.

Methylation Status of Transcriptional Modulatory Genes Associated with Colorectal Cancer in Northeast China.
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中国东北地区结直肠癌相关转录调节基因甲基化状况

DOI:
10.5009/gnl17163
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发表时间:
2018-03-15
期刊:
影响因子:
3.4
通讯作者:
Liu YP
Liu YP
中科院分区:
医学3区
文献类型:
--
作者:
Gao HL;Wang X;Sun HR;Zhou JD;Lin SQ;Xing YH;Zhu L;Zhou HB;Zhao YS;Chi Q;Liu YP

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背景/目的甲基化状态在靶组织的癌变中起因果作用。然而,血液白细胞中多个基因的DNA甲基化状态与结直肠癌(CRC)易感性之间的关系以及饮食因素与结直肠癌风险之间的相互作用尚不清楚。方法对466例结直肠癌患者和507例无癌患者进行病例对照研究,探讨个体基因甲基化状态、多CpG位点甲基化(MCSM)、多CpG位点异质甲基化与结直肠癌易感性之间的关系。外周血DNA甲基化水平通过进行甲基化敏感的高分辨率熔化检测。结果CA10和WT1的总异质甲基化导致CRC的风险显著增加(校正优势比[ORadjusted], 5.445; 95%可信区间[CI], 3.075 ~ 9.643; ORadjusted, 1.831; 95% CI, 1.100 ~ 3.047)。高MCSM (MCSM- h)状态的受试者患CRC的风险更高(or校正,4.318;95% CI, 1.529至12.197)。此外,高水平摄入水果与CRH、WT1和MCSM对结直肠癌的相互作用具有统计学意义。结论血液白细胞基因甲基化状态可能与结直肠癌风险相关。血白细胞MCSM-H与结直肠癌相关,尤其是在年轻人中。一些饮食因素可能影响高甲基化状态并影响结直肠癌的易感性。
Background/Aims Methylation status plays a causal role in carcinogenesis in targeted tissues. However, the relationship between the DNA methylation status of multiple genes in blood leukocytes and colorectal cancer (CRC) susceptibility as well as interactions between dietary factors and CRC risks are unclear. Methods We performed a case-control study with 466 CRC patients and 507 cancer-free controls to investigate the association among the methylation status of individual genes, multiple CpG site methylation (MCSM), multiple CpG site heterogeneous methylation and CRC susceptibility. Peripheral blood DNA methylation levels were detected by performing methylation-sensitive high-resolution melting. Results Total heterogeneous methylation of CA10 and WT1 conferred a significantly higher risk of CRC (adjusted odds ratio [ORadjusted], 5.445; 95% confidence interval [CI], 3.075 to 9.643; ORadjusted, 1.831; 95% CI, 1.100 to 3.047; respectively). Subjects with high-level MCSM (MCSM-H) status demonstrated a higher risk of CRC (ORadjusted, 4.318; 95% CI, 1.529 to 12.197). Additionally, interactions between the high-level intake of fruit and CRH, WT1, and MCSM on CRC were statistically significant. Conclusions The gene methylation status of blood leukocytes may be associated with CRC risk. MCSM-H of blood leukocytes was associated with CRC, especially in younger people. Some dietary factors may affect hypermethylation status and influence susceptibility to CRC.
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