Department of Experimental and Diagnostic Medicine and Interdepartmental Center for Research on Cancer, Ferrara University, Via Luigi Borsari 4-6, Ferrara, Italy.
Dis Esophagus. 2010 Sep;23(7):597-602. doi: 10.1111/j.1442-2050.2010.01059.x. Epub 2010 Apr 29.
It is known that obesity and occupational airborne exposure such as dust are among risk factors of esophageal cancer development, in particular squamous cell carcinoma (SCC) of esophagus. Here, we tested whether these factors could also affect aberrant DNA methylation. DNAs from 44 fresh tumor tissues and 19 non-tumor adjacent normal tissues, obtained from 44 patients affected by SCC of esophagus (SCCE), were studied for methylation at the CDKN2A/p16 gene promoter by methylation-specific polymerase chain reaction assay. Statistical methods were used to assess association of promoter methylation with biopathological, clinical, and personal information data, including obesity and airborne exposures. Methylation at the CDKN2A/p16 gene promoter was detected in 12 out of 44 tumor samples. None of the non-tumor tissues exhibited the aberrant methylation. Our results confirmed previously described significant association with low tumor stage (P= 0.002); in addition, we found that obesity (P= 0.001) and occupational exposure (P= 0.008) were both significantly associated with CDKN2A/p16 promoter methylation. This study provides evidence that obesity and occupational exposure increase the risk of developing esophageal cancer through an enhancement of CDKN2A/p16 promoter methylation.
已知肥胖和职业性空气传播暴露（如灰尘）是食管癌发展的危险因素，特别是食管鳞状细胞癌（SCC）。在这里，我们测试了这些因素是否也会影响异常的 DNA 甲基化。对 44 例食管 SCC（SCCE）患者的 44 例新鲜肿瘤组织和 19 例非肿瘤相邻正常组织中的 DNA 进行了 CDKN2A/p16 基因启动子甲基化的甲基化特异性聚合酶链反应分析。统计学方法用于评估启动子甲基化与生物病理学、临床和个人信息数据（包括肥胖和空气传播暴露）的关联。在 44 个肿瘤样本中的 12 个中检测到 CDKN2A/p16 基因启动子的甲基化。没有一个非肿瘤组织表现出异常甲基化。我们的结果证实了先前描述的与低肿瘤分期的显著相关性（P=0.002）；此外，我们发现肥胖（P=0.001）和职业暴露（P=0.008）均与 CDKN2A/p16 启动子甲基化显著相关。这项研究提供了证据表明，肥胖和职业暴露通过增强 CDKN2A/p16 启动子甲基化，增加了患食管癌的风险。
