Ally Mina Sarah, Al-Ghnaniem Reyad, Pufulete Maria
Diet and Gastrointestinal Health Group, Department of Nutrition and Dietetics, King's College London, Franklin Wilkins Building, 150 Stamford Street, London SE1 9NH, United Kingdom.
Cancer Epidemiol Biomarkers Prev. 2009 Mar;18(3):922-8. doi: 10.1158/1055-9965.EPI-08-0703. Epub 2009 Mar 3.
CpG island methylation in the promoter regions of tumor suppressor genes has been shown to occur in normal colonic tissue and can distinguish between subjects with and without colorectal neoplasms. It is unclear whether this relationship exists in other tissues such as blood. We report the relationship between estrogen receptor gene (estrogen receptor alpha) methylation in leukocyte and normal colonic tissue DNA in subjects with and without colorectal neoplasia. DNA was extracted from frozen stored whole blood samples of 27 subjects with cancer, 30 with adenoma, 16 with hyperplastic polyps, and 57 disease-free subjects. DNA methylation in seven CpG sites close to the transcription start of estrogen receptor alpha was quantitated using pyrosequencing and expressed as a methylation index (average methylation across all CpG sites analyzed). Estrogen receptor alpha methylation in leukocyte DNA was compared with estrogen receptor alpha methylation in normal colonic mucosa DNA that had been previously determined in the same subjects. Estrogen receptor alpha was partially methylated (median, 4.3%; range, 0.0-12.6%) in leukocyte DNA in all subjects, with no significant difference between disease groups (P>0.05). Estrogen receptor alpha methylation in leukocytes was 60% lower than estrogen receptor alpha methylation in normal colonic tissue (P<0.001). Estrogen receptor alpha methylation in colonic tissue (P<0.001) and smoking (P=0.016) were determinants of estrogen receptor alpha methylation in leukocytes, independent of age, body mass index, gender, and disease status. In conclusion, there was a positive relationship between estrogen receptor alpha methylation in leukocytes and colonic tissue in subjects with and without colorectal tumors. However, unlike in colonic tissue, estrogen receptor alpha methylation in leukocytes was unable to distinguish between disease groups.
肿瘤抑制基因启动子区域的CpG岛甲基化已被证明在正常结肠组织中会发生，并且可以区分有无结直肠肿瘤的受试者。尚不清楚这种关系在血液等其他组织中是否存在。我们报告了有和无结直肠肿瘤形成的受试者白细胞中雌激素受体基因（雌激素受体α）甲基化与正常结肠组织DNA之间的关系。从27例癌症患者、30例腺瘤患者、16例增生性息肉患者和57例无病受试者的冷冻保存全血样本中提取DNA。使用焦磷酸测序法定量分析雌激素受体α转录起始位点附近7个CpG位点的DNA甲基化情况，并表示为甲基化指数（所有分析的CpG位点的平均甲基化水平）。将白细胞DNA中的雌激素受体α甲基化与先前在同一受试者中测定的正常结肠黏膜DNA中的雌激素受体α甲基化进行比较。所有受试者白细胞DNA中的雌激素受体α均呈部分甲基化（中位数为4.3%；范围为0.0 - 12.6%），疾病组之间无显著差异（P>0.05）。白细胞中的雌激素受体α甲基化比正常结肠组织中的雌激素受体α甲基化低60%（P<0.001）。结肠组织中的雌激素受体α甲基化（P<0.001）和吸烟（P = 0.016）是白细胞中雌激素受体α甲基化的决定因素，独立于年龄、体重指数、性别和疾病状态。总之，在有和无结直肠肿瘤的受试者中，白细胞和结肠组织中的雌激素受体α甲基化之间存在正相关关系。然而，与结肠组织不同，白细胞中的雌激素受体α甲基化无法区分疾病组。
