Neale Rachel E, Clark Paul J, Fawcett Jonathan, Fritschi Lin, Nagler Belinda N, Risch Harvey A, Walters Rhiannon J, Crawford William J, Webb Penelope M, Whiteman David C, Buchanan Daniel D
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Cancer Epidemiol. 2014 Oct;38(5):576-82. doi: 10.1016/j.canep.2014.08.006. Epub 2014 Sep 5.
Pancreatic cancer is a leading cause of cancer-related deaths worldwide. Methylation of DNA may influence risk or be a marker of early disease. The aim of this study was to measure the association between methylation of three DNA repetitive elements in white blood cell (WBC) DNA and pancreatic cancer. DNA from WBCs of pancreatic cancer cases (n=559) and healthy unrelated controls (n=603) were tested for methylation of the LINE-1, Alu and Sat2 DNA repetitive elements using MethyLight quantitative PCR assays. Odds ratios (ORs) and 95% confidence intervals (95%CI) between both continuous measures of percent of methylated sample compared to a reference (PMR) or quintiles of PMR and pancreatic cancer, adjusted for age, sex, smoking, BMI, alcohol and higher education, were estimated. The PMR for each of the three markers was higher in cases than in controls, although only LINE-1 was significantly associated with pancreatic cancer (OR per log unit=1.37, 95%CI=1.16-1.63). The marker methylation score for all three markers combined was significantly associated with pancreatic cancer (p-trend=0.0006). There were no associations between measures of PMR and either presence of metastases, or timing of blood collection in relation to diagnosis, surgery, chemotherapy or death (all p>0.1). We observed an association between methylation of LINE-1 in WBC DNA and risk of pancreatic cancer. Further studies are needed to confirm this association.
胰腺癌是全球癌症相关死亡的主要原因之一。DNA甲基化可能影响患病风险或作为疾病早期的标志物。本研究的目的是测量白细胞（WBC）DNA中三种DNA重复元件的甲基化与胰腺癌之间的关联。使用甲基化荧光定量PCR检测法，对胰腺癌病例（n = 559）和健康无关对照（n = 603）的白细胞DNA进行LINE-1、Alu和Sat2 DNA重复元件甲基化检测。针对甲基化样本百分比（PMR）的连续测量值与参考值相比，或PMR五分位数与胰腺癌之间的比值比（OR）和95%置信区间（95%CI）进行估算，并对年龄、性别、吸烟、体重指数、饮酒和高等教育程度进行校正。尽管只有LINE-1与胰腺癌显著相关（每对数单位OR = 1.37，95%CI = 1.16 - 1.63），但三种标志物各自的PMR在病例组中均高于对照组。三种标志物综合的甲基化评分与胰腺癌显著相关（p趋势 = 0.0006）。PMR测量值与转移的存在或与诊断、手术、化疗或死亡相关的采血时间之间均无关联（所有p>0.1）。我们观察到白细胞DNA中LINE-1的甲基化与胰腺癌风险之间存在关联。需要进一步研究来证实这种关联。
