Associations of risk factors obesity and occupational airborne exposures with CDKN2A/p16 aberrant DNA methylation in esophageal cancer patients


  • Declaration of interests: The authors declare that they have no competing interests.

Dr. Massimo Negrini, PhD, Dipartimento di Medicina Sperimentale e Diagnostica e Centro Interdipartimentale per la Ricerca sul Cancro, Università di Ferrara, Via Luigi Borsari4 6 – 44100 Ferrara, Italy. Email:; Dr. Ferdous Rastgar-Jazii, PhD, Department of Biochemistry, National Institute of Genetic Engineering and Biotechnology, (NIGEB), Building A. Shahrak – e – Pajoohesh, Kilometer 15, Tehran–Karaj Highway, P. O. Box: 14965/161, Tehran, Iran. Email:


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.