Genomic methylation of leukocyte DNA in relation to colorectal adenoma among asymptomatic women
Genomic methylation of leukocyte DNA in relation to colorectal adenoma among asymptomatic women
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DOI：
10.1053/j.gastro.2007.10.013
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发表时间：
2008-01-01
期刊：
影响因子：
29.4
通讯作者：
Stolzenberg-Solomon, Rachael
中科院分区：
文献类型：
--
作者：
Lim, Unhee;Flood, Andrew;Stolzenberg-Solomon, Rachael
背景与目的：DNA甲基化的系统性抑制导致动物癌症，部分原因是诱导遗传不稳定性。然而，将系统性血液DNA中的低基因组甲基化与癌变联系起来的流行病学证据是有限的，特别是对于结肠直肠，其中遗传不稳定性是主要病因。我们检测了参与多中心结肠镜筛查研究（CONCeRN研究，2000-2002）的无症状女性（40 - 79岁）中与结直肠腺瘤（CRA）相关的白细胞DNA基因组甲基化。研究方法：在所有完成自我管理的风险因素和食物频率问卷、外周血捐献和结肠镜检查的参与者中，研究了115对CRA病例和对照组，这些病例和对照组具有匹配的年龄和抽血月份。采用液相色谱-质谱法测定白细胞DNA的基因组甲基化。条件Logistic回归用于估计比值比（OR）和95%置信区间（0）。结果如下：与基因组甲基化水平最低的三分位数的女性相比，第二（OR，0.72; 95% CI：0.34 - 1.52）和第三（OR，0.17; 95% CI：0.06-0.49）三分位数的女性CRA风险较低（P趋势= 0.002）。非进展期腺瘤的负相关性强于进展期腺瘤，近端腺瘤的负相关性弱于远端腺瘤。低叶酸摄入量比高叶酸摄入量的保护作用更强，但与1-碳代谢或结直肠癌风险因素相关的其他营养素没有差异。结论：我们关于无症状CRA的发现提示系统性基因组甲基化是早期CRA的潜在病因。
Background & Aims: Systemic inhibition of DNA methylation causes cancers in animals, in part by inducing genetic instability. Epidemiologic evidence linking low genomic methylation in systemic blood DNA to carcinogenesis is limited, however, specifically to the colorectum, in which genetic instability is a primary etiologic factor. We examined genomic methylation of leukocyte DNA in relation to colorectal adenoma (CRA) among asymptornatic women (40 -79 years of age) participating in a multicenter colonoscopy screening study (CONCeRN Study, 2000-2002). Methods: Of all participants who completed self-administered risk factor and food frequency questionnaires, peripheral blood donation, and colonoscopy, 115 pairs of CRA cases and controls with matching age and month of blood draw were studied. Genomic methylation of leukocyte DNA was determined by liquid chromatography mass spectrometry. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (0). Results: Compared with women in the lowest tertile of genomic methylation, women in the second (OR, 0.72; 95% CI: 0.34 -1.52) and third tertiles (OR, 0.17; 95% CI: 0.06-0.49) had lower risk of CRA (P trend =.002). The inverse relationship was stronger for nonadvanced than for advanced adenoma and, less notably, for proximal than for distal adenoma. The association was also moderately more protective with low rather than high total folate intake but did not differ by other nutrients involved in 1-carbon metabolism or colorectal cancer risk factors. Conclusions: Our findings regarding asymptomatic CRA implicate systemic genomic methylation as a potential etiologic factor for an early stage of CRA.