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Background  The hypermethylation of Alcohol dehydrogenase iron containing 1 ( ADHFE1 ) was recently reported to be associated with colorectal cancer (CRC) differentiation. However, the effect of alcohol on  ADHFE1  hypermethylation in CRC is still unclear.    Methods  The methylation status and expression levels of  ADHFE1  were investigated in primary tumor tissues and adjacent normal tissues of 73 patients with CRC, one normal colon cell line, and 4 CRC cell lines (HT-29, SW480, DLD-1, and LoVo) by quantitative methylation-specific polymerase chain reaction (QMSP) and real-time reverse transcription polymerase chain reaction (real time PCR), respectively. The effect of alcohol on the methylation status of  ADHFE1  was analyzed in HT-29, SW480, DLD-1, and CCD18Co cells using QMSP, real-time PCR, immunoblot, and cell proliferation assay.    Results   ADHFE1  was hypermethylated in 69 of 73 CRC tissues (95%) compared to adjacent normal tissues ( p  < 0.05). The mRNA expression of  ADHFE1  was significantly reduced in CRC compared to adjacent normal tissues ( p <  0.05) and its expression was decreased in the alcohol consumption group ( p <  0.05).  ADHFE1  was hypermethylated and its expression was decreased in 4 CRC cell lines compared with normal colon cell line. Alcohol induced hypermethylation of  ADHFE1 , decreased its expression, and stimulated cell proliferation of HT-29, SW480, and DLD-1cells.    Conclusion  These results demonstrate that the promoter hypermethylation of  ADHFE1  is frequently present in CRC and alcohol induces methylation-mediated down expression of  ADHFE1  and proliferation of CRC cells.

Alcohol induces cell proliferation via hypermethylation of ADHFE1 in colorectal cancer cells