A cross-sectional study of global DNA methylation and risk of colorectal adenoma.
A cross-sectional study of global DNA methylation and risk of colorectal adenoma.
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DOI：
10.1186/1471-2407-14-488
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发表时间：
2014-07-07
期刊：
影响因子：
3.8
通讯作者：
Vanner SJ
中科院分区：
文献类型：
--
作者：
King WD;Ashbury JE;Taylor SA;Tse MY;Pang SC;Louw JA;Vanner SJ
DNA甲基化被认为是一种关键的表观遗传机制，其在几种恶性肿瘤发展中的作用的证据正在积累。我们评估了来自正常结肠粘膜组织和血液白细胞的DNA的整体甲基化与结直肠腺瘤风险之间的关系。招募了40至65岁的患者，计划进行结肠镜检查。在结肠镜检查过程中，从降结肠获得两个健康、外观正常的粘膜捏取活检。还采集了空腹血样。LINE-1（长散在核元件-1）重复序列的甲基化状态，作为一个替代措施的全球甲基化，定量从正常结肠粘膜和血液白细胞提取的DNA。对317名参与者进行了总体DNA甲基化和腺瘤风险之间关系的统计分析，其中108名受试者至少有一个病理证实的腺瘤，209名受试者结肠镜检查正常。对于最低甲基化四分位数与最高甲基化四分位数，观察到男性和两种性别的结肠组织DNA中LINE-1甲基化与腺瘤风险之间存在统计学显著的负相关关系（校正OR分别为2.94和2.26）。对于血液，尽管比值比估计的总体模式是与最高甲基化四分位数相比，较低甲基化四分位数的风险增加，但未观察到统计学显著性关系。在组织和血液中测量的LINE-1甲基化水平之间发现中度相关性（Pearson相关性0.36）。我们观察到，在正常外观的背景结肠粘膜中，LINE-1 DNA甲基化水平较低与男性腺瘤风险增加相关，男女均如此。虽然这些发现为结肠粘膜组织中LINE-1 DNA甲基化与腺瘤风险之间的关系提供了一些支持，但需要大型前瞻性队列研究来证实结果。直到这样的研究完成，LINE-1甲基化作为腺瘤风险增加的生物标志物的临床用途是不确定的。无论如何，这项研究有助于更好地理解全球DNA甲基化作为CR癌变早期事件的作用，并对未来的病因学研究产生影响。
The methylation of DNA is recognized as a key epigenetic mechanism and evidence for its role in the development of several malignancies is accumulating. We evaluated the relationship between global methylation in DNA derived from normal appearing colon mucosal tissue and blood leukocytes, and colorectal adenoma risk. Patients, aged 40 to 65, scheduled for a screening colonoscopy were recruited. During the colonoscopy, two pinch biopsies of healthy, normal appearing mucosa were obtained from the descending colon. A fasting blood sample was also collected. The methylation status of LINE-1 (long interspersed nuclear element-1) repetitive sequences, as a surrogate measure of global methylation, was quantified in DNA extracted from normal colon mucosa and blood leukocytes. Statistical analysis of the relationship between global DNA methylation and adenoma risk was conducted on 317 participants, 108 subjects with at least one pathologically confirmed adenoma and 209 subjects with a normal colonoscopy. A statistically significant inverse relationship was observed between LINE-1 methylation in colon tissue DNA and adenoma risk for males and for both sexes combined for the lowest methylation quartile compared to the highest (adjusted ORs = 2.94 and 2.26 respectively). For blood, although the overall pattern of odds ratio estimates was towards an increase in risk for lower methylation quartiles compared to the highest methylation quartile, there were no statistically significant relationships observed. A moderate correlation was found between LINE-1 methylation levels measured in tissue and blood (Pearson correlation 0.36). We observed that lower levels of LINE-1 DNA methylation in normal appearing background colon mucosa were associated with increased adenoma risk for males, and for both sexes combined. Though these findings provide some support for a relationship between LINE-1 DNA methylation in colon mucosal tissue and adenoma risk, large prospective cohort studies are needed to confirm results. Until such investigations are done, the clinical usefulness of LINE-1 methylation as a biomarker of increased adenoma risk is uncertain. Regardless, this study contributes to a better understanding of the role of global DNA methylation as an early event in CR carcinogenesis with implications for future etiologic research.
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影响因子：
3.3
作者：
Giacosa, A;Frascio, F;Munizzi, F
通讯作者：
Munizzi, F
影响因子：
56.9
作者：
Gaudet, F;Hodgson, JG;Jaenisch, R
通讯作者：
Jaenisch, R
影响因子：
56.9
作者：
GOELZ, SE;VOGELSTEIN, B;FEINBERG, AP
通讯作者：
FEINBERG, AP
DOI：
10.1097/00008469-199411000-00004
发表时间：
1994-11-01
期刊：
European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)
影响因子：
--
作者：
Cravo, M;Fidalgo, P;Leitao, C N
通讯作者：
Leitao, C N
影响因子：
30.8
作者：
Faulkner, Geoffrey J.;Kimura, Yasumasa;Carninci, Piero
通讯作者：
Carninci, Piero