LINE-1 hypomethylation in noncancerous esophageal mucosae is associated with smoking history.

Abstract

BACKGROUND:

Cancer cells exhibit two types of DNA methylation alterations: global DNA hypomethylation and site-specific CpG island promoter hypermethylation. Selected gene promoter hypermethylation in normal esophageal mucosae has attracted attention as a surrogate marker for the epigenetic field defect induced by smoking and/or drinking in esophageal squamous cell carcinoma (ESCC). However, the significance of global DNA hypomethylation for field cancerization remains unclear.

METHODS:

By using histologically normal esophageal mucosa samples from 109 ESCC cases and 20 autopsy cases without ESCCs, we measured long interspersed nucleotide element 1 (LINE-1) methylation levels by pyrosequencing, which correlates with global DNA methylation level.

RESULTS:

LINE-1 methylation levels in normal esophageal mucosae of ESCC patients were significantly lower than those of autopsy individuals (P = 0.017). LINE-1 methylation of noncancerous mucosae ranged 68.3-93.0 on a 0-100 scale (mean 81.7, median 82.2, standard deviation 5.9). LINE-1 hypomethylation was significantly associated with smoking history (P = 0.014 for smoking duration; P = 0.0017 for number of cigarettes per day; P = 0.0002 for tobacco pack-year). LINE-1 methylation was not associated with alcohol drinking or age at diagnosis.

CONCLUSIONS:

A history of tobacco use was significantly associated with LINE-1 hypomethylation in noncancerous esophageal mucosae of ESCC patients. These results support the potential of LINE-1 methylation level as an indicator of epigenetic field for ESCC cancerization, particularly when caused by tobacco smoking.

• Authors: Hironobu Shigaki, Yoshifumi Baba, Masayuki Watanabe, Shiro Iwagami, Keisuke Miyake, Takatsugu Ishimoto, Masaaki Iwatsuki, Hideo Baba
• Journal: Annals of surgical oncology (Ann Surg Oncol) Vol. 19 Issue 13 Pg. 4238-43 (Dec 2012) ISSN: 1534-4681 [Electronic] United States
• PMID: 22766991 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA

Topics

• Aged
• Aged, 80 and over
• Carcinoma, Squamous Cell (etiology)
• Case-Control Studies
• DNA (genetics)
• DNA Methylation
• Epigenomics
• Esophageal Neoplasms (etiology)
• Esophagus (metabolism, pathology)
• Female
• Follow-Up Studies
• Humans
• Long Interspersed Nucleotide Elements (genetics)
• Male
• Middle Aged
• Mucous Membrane (metabolism)
• Polymerase Chain Reaction
• Prognosis
• Risk Factors
• Smoking (adverse effects, genetics)